器官移植

2018 Vol. 9, No. 3

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Editorial
Original Articles Experimental Researches
Original Articles Experimental Researches
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Editorial

2018, 9(3): 169-173. doi: 10.3969/j.issn.1674-7445.2018.03.001

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Original Articles Experimental Researches

Mechanism of coagulation dysfunction in the recipients mediated by tissue factor activation after liver xenotransplantation

Wu Enhao, Li Xiao, Tao Kaishan

2018, 9(3): 174-180. doi: 10.3969/j.issn.1674-7445.2018.03.002

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Objective To investigate the mechanism underlying the activation of tissue factor (TF) that leads to coagulation dysfunction in the recipients after liver xenotransplantation. Methods Auxiliary heterotopic liver xenotransplantation was performed in 3 minipigs with α-1, 3-galactosyltransferase gene-knockout (GTKO) as the donors and Tibetan macaque (Macaca thibetana) as the recipients. Postoperative coagulation function changes in the recipients were observed. Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining were adopted to quantitatively measure the expression levels of monkey and minipig TF messenger RNA (mRNA) and protein in the liver tissues of the primary and transplant livers at different time points before and after transplantation. The recalcification time of peripheral blood mononuclear cell (PBMC) was recorded in the normal control monkeys and the recipient monkeys before and 2 h after liver transplantation to evaluate the coagulation status in the recipients. Results All three recipients presented with different degrees of coagulation dysfunction after surgery, manifested as a decrease in fibrinogen level and a reduction in platelet count. The monkey TF protein was positively expressed in the primary livers after surgery, whereas negatively expressed in transplant livers before and after liver transplantation. The minipig TF protein was negatively expressed in both primary livers and transplant livers. At postoperative 2 h, monkey TF mRNA was up-regulated by (2.10±0.24) times in the primary liver compared with the preoperative level, whereas the minipig TF mRNA was up-regulated by (1.42±0.15) times compared with preoperative level. There was statistical significance between the primary livers and transplant livers ( P=0.014). Compared with PBMC in the normal control monkeys and recipient monkeys before liver transplantation, the recalcification time of the PBMC in the recipient monkeys was significantly shortened at postoperative 2 h (both P < 0.001). Conclusions At the presence of coagulation dysfunction after liver xenotransplantation, the level of TF activation in the primary livers is significantly higher than that in the transplant livers. The TF activation in the primary livers is the main cause of coagulation dysfunction after liver xenotransplantation.

Study of immunoregulatory effect of sirolimus on xenotransplantaion with arterial patch

Zhang Qing, Zhou Cuibing, Wang Chengjun, Cai Zhiming, Mou Lisha

2018, 9(3): 181-187. doi: 10.3969/j.issn.1674-7445.2018.03.003

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Objective To investigate the immunoregulatory effect of sirolimus on the xenotransplantation with arterial patch. Methods The xenotransplantation of arterial grafts was taken from the wild-type Bama pigs to cynomolgus monkeys. The peripheral blood mononuclear cells of recipient monkeys at 14 days after xenotransplantation (POD14) were selected as subjects. Dimethyl sulphoxide (DMSO) was used in the control group (volume ratio of 1:1 000) and sirolimus was administered in the sirolimus experimental group (final concentration of 0.1 μmol/L and 0.5 μmol/L). The cells were cultured for 1.0 and 5.5 d, respectively. The activity of POD14 cells was evaluated. The DMSO control and sirolimus experimental groups (final concentration of 0.1 μmol/L) were established and cultured for 5.5 d. The quantity of T and B cells in POD14 cells was counted and the expression levels of cytokines and messenger RNA (mRNA) were quantitatively measured. Results Compared with the DMSO control group, the activity of POD14 cells was significantly decreased after sirolimus treatment at a final concentration of 0.1 and 0.5 μmol/L for 1.0 d ( P < 0.01-0.001). After sirolimus treatment at a final concentration of 0.1 and 0.5 μmol/L for 5.5 d, the activity of POD14 cells was significantly decreased (both P < 0.001). Compared with the DMSO control group, the quantity of CD3⁺CD4⁺ T cells and CD3⁺CD8⁺T cells in POD14 cells was significantly reduced after sirolimus treatment at a final concentration 0.1 μmol/L ( P < 0.05-0.01), whereas the quantity of CD3^-CD20⁺B cells was considerably elevated ( P < 0.01). Compared with DMSO control group, the levels of interferon(IFN)-γ, interleukin(IL)-2, IL-4, IL-5 and IL-6 in the sirolimus experimental group were significantly down-regulated ( P < 0.05-0.001). The expression levels of IFN-γ, tumor necrosis factor(TNF)-α, IL-2, IL-4, IL-5 and IL-6 mRNA were significantly down-regulated ( P < 0.05-0.001). Conclusions Sirolimus inhibits the proliferation of POD14 cells in the recipient monkeys after xenotransplantation with arterial patch. The underlying mechanism is that the sirolimus can reduce the quantity of T cells and suppress the expression and secretion of immune rejection-related cytokines.

Study of isolation efficiency of new islet isolation solution for mouse islets

Li Rui, Dong Hongli, Liu Baolin

2018, 9(3): 188-193. doi: 10.3969/j.issn.1674-7445.2018.03.004

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Objective To investigate the isolation and protective effect of a new islet purification solution (IPS)- Optiprep solution on the islet in mouse models. Methods The digested pancreatic islets were divided into the IPS andUW groups according to the islet volume. The pancreatic islets were isolated by the continuous gradient density centrifugation using IPS-Optiprep or UW-Optiprep solutions. The purification efficiency and isolated islet activity of purification solution were compared between two groups. The diabetic mouse models were successfully induced and randomly assigned into three groups. In the experimental group (n=10), the mice received pancreatic islet transplantation using islets isolated and purified by the IPS-Optiprep solution. In the control group (n=10), the mice underwent pancreatic islet transplantation using islets isolated and purified by the UW-Optiprep solution. In the sham surgery group (n=5), the mice merely underwent surgery without pancreatic islet transplantation. Postoperative blood glucose levels were detected and compared among three groups. The blood glucose levels of intraperitoneal glucose tolerance test at postoperative 21 d were statistically compared between the experimental and control groups. The cost of the preparation of two isolation solutions was also compared. Results Compared with the UW group, the islet equivalent (IEQ), islet purity, recovery rate and islet integrity were significantly higher in the IPS group. Islet morphological observation revealed that the islet membrane was complete and the islet diameter in the IPS group was considerably larger than that in the UW group. The activity of purified islets in the UW group was significantly higher than that in the IPS group [(88±5)% vs. (84±3)%, P < 0.01]. Compared with the UW-Optiprep solution, identical in vivo islet function was obtained in the IPS-Optiprep solution. The cost of IPS-Optiprep solution was significantly less than that of the UW-Optiprep solution. Conclusions The new IPS-Optiprep solution yields higher islet isolation efficiency, purification, integrity and recovery rate and significantly reduces the purification cost compared with the UW-Optiprep solution. Nevertheless, IPS-Optiprep solution exerts a less protective effect on the activity of islet cells, which is probably correlated with the high islet integrity and the endotoxin in the IPS-Optiprep solution.

Study of miR-155 in the mechanism of rejection after liver transplantation in rats

Li Kun, Kong Weihao, Zhang Junbin, Chen Qiangxing, Sun Chong, Yin Dongliang, Li Hui, Zhang Jian

2018, 9(3): 194-199. doi: 10.3969/j.issn.1674-7445.2018.03.005

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Objective To explore the mechanism of microRNA (miRNA, miR)-155 in the rejection after liver transplantation in rats. Methods The rats were divided into two groups. In the xenograft model group (rejection group, n=10), the donors were male Lewis rats and the recipients were male BN rats. In the allograft model group (control group, n=10), both the donors and recipients were male Lewis rats. The rat models with orthotopic liver transplantation were established by two-cuff technique in two groups. At postoperative 7 d, the animals were sacrificed for the collection of blood and liver tissue samples. The serum levels of alanine aminotransferase (ALT), total bilirubin (TB), and cytokines of interleukin (IL)-2, IL-4, interferon (IFN)-γ were quantitatively measured. The pathological changes of liver tissues were observed under light microscope. In each group, three liver tissue samples were prepared and subject to high-throughput sequencing. The miRNAs related to rejection were identified for bioinformatics analysis to predict and analyze relevant signaling pathways and genes. Results In the rejection group, the serum levels of ALT and TB were significantly higher than those in the control group (both P < 0.01). Compared with the control group, the levels of IL-2 and IFN-γ were considerably up-regulated (both P < 0.01), whereas the level of IL-4 was dramatically down-regulated ( P < 0.01). Pathological examination demonstrated that more evident rejections were observed in the rejection group than the control group. High-throughput sequencing revealed that the expression level of miR-155 was significantly up-regulated in the rejection group, which was 5.89 times of that in the control group. Bioinformatics analysis demonstrated that up-regulation of miR-155 was associated with the mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK) and T cell receptor signaling pathways. The genes which were probably responsible for regulation included the yeast autophagy related gene 1(ATG1) and its homologous gene ULK2, insulin-like growth factor-1 (Igf-1) and G protein-coupled receptor regulatory gene (Arrb1), etc. Conclusions miR-155 might promote the incidence and progression of rejection after liver transplantation in rats. The involved signaling pathways probably include the mTOR, MAPK signaling pathway and T cell receptor signaling pathway. ATG1, ULK2, Igf-1, and Arrb1 genes may participate in this process.

Original Articles Experimental Researches

Development of magnetic spiderman to optimize the procedures of repairment of donor liver from organ donation

Tian Boyan, Dong Dinghui, Wang Yue, Liu Xuemin, Xiang Junxi, Zhu Haoyang, Lyu Yi

2018, 9(3): 200-204. doi: 10.3969/j.issn.1674-7445.2018.03.006

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Objective To develop a pulling device using magnetic positioning to optimize the procedures of repairment of donor liver from organ donation. Methods The pig liver specimens were used to measure the pull force of repairment of donor liver, magnetic spiderman was developed based on the measurement results. The magnetic spiderman was applied to simulate the repairment of donor liver from organ donation on the pig liver specimens. The effectiveness of magnetic spiderman was also evaluated. Results The pulling force was required all less than 2 N during the repairment of donor liver. The magnetic spiderman was successfully manufactured. The magnets of magnetic spiderman could generate 3 N magnetic forces with paramagnetic basin of hepatic repairment. The self-retraction pull wire of the magnetic spiderman could provide 2.5 N pulling forces. The magnetic spiderman was successfully applied to the simulated experiment of repairment of donor liver from organ donation in 6 cases. The operation time was (54±5) min. No clip slippage, displacement and slippage of the base occurred during the operation. With the cooperation of multiple magnetic spidermen, the remaining surgical procedures were performed by one single surgeon except for the vascular ligation. Conclusions The magnetic spiderman has small volume and implements flexible positioning, can perform pulling operation and not take up operational space. It can effectively optimize the procedures of repairment of donor liver from organ donation and reduce the quantity of surgeons.

Editorial Experimental Researches

High-throughput sequencing analysis of single nucleotide polymorphism loci mutation in genes associated with acute rejection in liver transplantation

Bao Yuanda, Yi Shuhong

2018, 9(3): 205-210. doi: 10.3969/j.issn.1674-7445.2018.03.007

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Objective To analyze the mutation of single nucleotide polymorphism (SNP) loci in genes most significantly associated with acute rejection after liver transplantation by high-throughput sequencing. Methods Peripheral blood samples were collected from 68 recipients undergoing allogeneic orthotopic liver transplantation. According to the incidence of acute rejection, all patients were divided into the acute rejection group (n=13) and non-rejection group (n=55). Through the literature review, 44 mutant SNP loci associated with acute rejection were finally identified. Using 44 SNP loci as the detection targets, high-throughput sequencing analysis was performed to detect peripheral blood samples in two groups of recipients. Bioinformatics analysis revealed the mutation rate of the SNP loci of genes related to acute rejection. Results The mutation rate of SNP loci of the interleukin (IL)-10 TT genotype, T allele, AA genotype and A allele in the acute rejection group was significantly higher than that in the non-rejection group. The mutation rate of the SNP loci of the cell chemokine receptor (CCR) 5 AG genotype in the acute rejection group was significantly lower than that in the non-rejection group, the mutation rate of the SNP loci of the CCR5 GG genotype in the acute rejection group was significantly higher than that in the non-rejection group. The mutation rate of the SNP loci of IL-4 CT genotype in the acute rejection group was significantly higher than that in the non-rejection group, the mutation rate of the SNP loci of IL-4 TT genotype in the acute rejection group was significantly lower than that in the non-rejection group. The mutation rate of the SNP loci of nuclear factor-kappa B inhibitor alpha(NF-κBIA) C allele in the acute rejection group was significantly higher than that in the non-rejection group. The mutation rate of the SNP loci of vitamin D receptor (VDR) CC genotype and C allele in the acute rejection group was significantly lower than that in the non-rejection group. Differences were statistically significant (all P < 0.05). Conclusions High-throughput sequencing analysis shows the genes associated with acute rejection after liver transplantation. Among them, the mutation rate of the SNP loci is relatively high in IL-10 TT genotype, T allele, AA genotype, A allele, CCR5 GG genotype, AG genotype, IL-4 CT genotype, TT genotype, NF-κBIA C allele, VDR CC genotype and C allele.

Clinical Researches

Effect of the ratio of living related donor renal volume to recipient body surface area on early function of transplanted kidney

Gu Dongfeng, Zhao Yunfeng, Miao Shuzhai, Qu Qingshan

2018, 9(3): 211-214. doi: 10.3969/j.issn.1674-7445.2018.03.008

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Objective To investigate the relationship between the ratio of living related donor renal volume (RV) to recipient body surface area (BSA) (RV/BSA) and early postoperative function of transplanted kidney. Methods Clinical data of 120 pairs of donors and recipients undergoing living related renal transplantation were retrospectively analyzed. According to the RV/BSA ratio, the recipients were divided into group A (RV/BSA < 65.33 mL/m²), group B (RV/BSA 65.33~76.49 mL/m²), group C (RV/BSA 76.50~96.96 mL/m²) and group D (RV/BSA > 96.96 mL/m²). The postoperative estimated glomerular filtration rate (eGFR) of recipients was compared among 4 groups. The correlation between the RV/BSA and eGFR of recipients at postoperative 6 and 12 months was analyzed. Results The eGFR at postoperative 6 month in group A was significantly lower than that in groups B, C and D (t=2.313, 2.947, 5.903; all P < 0.05). The eGFR at postoperative 12 month in group A was also significantly lower than that in groups B, C and D (t=2.189, 2.433, 2.909; all P < 0.05). The RV/BSA was significantly correlated with the eGFR of recipients at postoperative 6 and 12 months (all P < 0.05). Conclusions RV/BSA is intimately correlated with the early function of transplanted kidney after living related renal transplantation.

Clinical diagnosis and treatment of intestinal complications after renal transplantation

Yang Qishun, Jiang Wei, Huang Chibing

2018, 9(3): 215-221. doi: 10.3969/j.issn.1674-7445.2018.03.009

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Objective To investigate the etiology, clinical characteristics, diagnosis and treatment of intestinal complications after renal transplantation. Methods Clinical data of 47 patients presenting with intestinal complications following renal transplantation were retrospectively analyzed. The etiology, clinical characteristics and treatment experience of intestinal complications were summarized. Results Forty-seven patients with intestinal complications after renal transplantation were followed up for 3-36 months with the median time of 18 months. Intestinal complications included the upper gastrointestinal bleeding in 4 cases, the lower gastrointestinal bleeding in 1 case, acute enteritis in 25 cases, chronic enteritis in 12 cases, intestinal tuberculosis in 1 case, colon cancer in 1 case, and intestinal obstruction in 3 cases, respectively. Among patients with gastrointestinal bleeding, the symptoms occurred after the use of high-dose adrenal cortex hormone in 4 cases and 2 patients developed hemorrhagic shock. In patients with acute enteritis, 7 cases received immunosuppressants for the first time during the perioperative period of renal transplantation, the remaining 18 patients had dirty diet or catched cold and 4 were positive for pathogens. Among patients with chronic enteritis, plasma concentrations of mycophenolic acid or tacrolimus were elevated in 12 patients, water, electrolyte, and acid-base imbalance was detected, 2 were positive for pathogens, and 8 were accompanied with severe anemia. One case of intestinal obstruction occurred during the perioperative period of renal transplantation, and 2 cases experienced toxic shock. According to the type and severity of disease, symptomatic and etiological treatments were actively implemented. In the 47 patients, 45 were cured and 2 died from the lower gastrointestinal bleeding and respiratory failure caused by lung metastasis of colon cancer. Three patients suffered from transplanted renal insufficiency. Conclusions The intestinal complications after renal transplantation are diverse, which are correlated with the imbalance of intestinal homeostasis. Both the acute and chronic diseases can cause various degrees of damage to the function of transplanted kidneys. Clinical prognosis is poor at the presence of severe complications. Active prevention and management should be implemented to reduce the risk of postoperative complications and enhance the cure rate.

Analysis of early clinical efficacy of renal transplantation from extended criteria donor of the donation after cardiac death

Ruan Dongli, Zhang Geng, Liu Kepu, Li Zhibin, Gao Long, Zheng Wenfeng, Wang Huilong, Yuan Jianlin

2018, 9(3): 222-226. doi: 10.3969/j.issn.1674-7445.2018.03.010

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Objective To compare the early clinical efficacy of renal transplantation between extended criteria donor (ECD) and standard criteria donor (SCD). Methods Clinical data of 85 recipients undergoing renal transplantation from donation after cardiac death (DCD) were retrospectively analyzed. According to the types of donors, all recipients were divided into the ECD group (n=31) and SCD group (n=54). The level of serum creatinine (Scr), incidence of early complications and clinical prognosis within 3 months after renal transplantation were compared between 2 groups. Results No statistical significance was observed in the levels of Scr within 1 month after renal transplantation between the ECD group and SCD group (all P > 0.05). At postoperative 60 and 90 d, the level of Scr in the ECD group was (189±97) and (175±69) μmol/L respectively, significantly higher than (142±49) and (135±41) μmol/L in the SCD group (P=0.005 and 0.002). In the ECD group and SCD group, the incidence of acute rejection (AR) was 6% and 15%, the incidence of delayed graft function (DGF) was 23% and 19%, the incidence of pulmonary infection was 10% and 6%, the incidence of other early complications was 32% and 15%, respectively, no statistical significance was identified (all P > 0.05). In the ECD group and SCD group, the survival rate of the recipient was 97% and 94%, the survival rate of the renal was 84% and 91%, no statistical significance was identified (all P > 0.05). Conclusions Compared with the SCD, renal transplantation from ECD can achieve equivalent early clinical efficacy. In the present condition of serious deficiency of donor kidney, the application of ECD can enlarge the supply of the donor kidney.

Application of small-for-size graft of pediatric donor liver transplantation in an adult recipient with acute liver failure: a report of one case and literature review

Ye Zhenghui, Zhao Hongchuan, Huang Fan, Wang Guobin, Yu Xiaojun, Hou Liujin

2018, 9(3): 227-231. doi: 10.3969/j.issn.1674-7445.2018.03.011

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Objective To summarize the clinical experience of small-for-size graft of pediatric donor liver transplantation in the treatment of acute liver failure in an adult recipient. Methods Clinical data of application of small-for-size graft of pediatric donor liver transplantation in an adult recipient was retrospectively analyzed and literature review was performed. Results The pediatric donor was aged 4.5 years old and the weight of donor liver from donation after brain death was 544.6 g. The body mass of recipient was 52 kg. The graft-to-recipient weight ratio was 1.05%. The classic orthotopic liver transplantation was performed. Postoperative recovery was not satisfying. The recipient suffered from brain edema, stress gastrointestinal bleeding, acute kidney injury, small-for-size liver syndrome, atelectasis, lung infection, fungal infection, abdominal infection, pleural effusion and other postoperative complications. After symptomatic and comprehensive treatment, the function of liver graft was gradually restored and regenerated to the normal size of adult liver at postoperative 2 to 3 weeks. The patient was discharged after 102 d hospitalization. During the follow-up at postoperative 10 months, the liver function was evaluated normal and the quality of life was favorable. Conclusions Pediatric small-for-size donor livers can be successfully transplanted to the adult recipients. Nevertheless, it is necessary to select the appropriate recipients, surgical methods and fine perioperative management according to the conditions of the donor livers.

Brucellosis after renal transplantation: a report of one case and literature review

Ma Xihui, Xiao Li, Qian Yeyong, Li Chao, Shi Bingyi

2018, 9(3): 232-235. doi: 10.3969/j.issn.1674-7445.2018.03.012

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Objective To analyze and summarize the clinical features and diagnosis and treatment experience of brucellosis after renal transplantation. Methods Clinical data of one case with brucellosis after renal transplantation admitted to the 309th Hospital of Chinese People's Liberation Army in October 2016 was collected. The clinical features, diagnosis and treatment were retrospectively analyzed. Clinical experience was summarized and literature review was conducted. Results At 3 months after renal transplantation, the patient suffered from temperature rise without known causes and presented with fever in the morning with a duration of 3 d. The route of infection was unknown, and the symptoms of alternative types of infection were not obvious. Empirical anti-infectious therapy was delivered for 1 week and yielded no efficacy. Blood culture test confirmed the diagnosis of brucella melitensis infection. The treatment included anti-infecting by the rifampicin, doxycycline, sulfamethoxazole, preventing the incidence of complications actively and protecting the liver and renal function. High clinical efficacy was achieved. During the 1-year follow up after discharge, the renal graft was stable and no other infectious symptoms, such as fever was found. Conclusions Brucellosis with unknown route of infection after renal transplantation is extremely rare and the common symptom is Malta fever. When the empirical anti-infectious treatment is not effective, blood culture and other related tests should be performed to confirm the diagnosis. The combination of rifampicin and doxycycline is recommended.

Reviews

2018, 9(3): 236-238. doi: 10.3969/j.issn.1674-7445.2018.03.013

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2018, 9(3): 239-241. doi: 10.3969/j.issn.1674-7445.2018.03.014

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2018, 9(3): 242-244. doi: 10.3969/j.issn.1674-7445.2018.03.015

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