1.The effect of new-onset diabetes after renal transplantation on arterial stiffness
Hang LIU ; Yi SHI ; Zhongyang SHEN
Chinese Journal of Organ Transplantation 2009;30(7):415-418
Objective To investigate the risk factor for new-onset diabetes after transplantation (NODAT) and the relationship between NODAT and arterial stiffness. Methods Oral glucose tolerance test (OGTT) was performed on 195 patients with renal transplantation. The degree of arterial stiffness, which was determined by brachial ankle pulse wave velocity (baPWV), anklebrachial blood pressure index (ABPI) and intima-media thickness (IMT) of the carotid artery, was evaluated. Results Twenty-nine patients diagnosed as NODAT had significantly higher fasting plasma glucose before transplantation, blood pressure and incidence of hepatitis C virus (HCV) infection than in patients without NODAT. Multivariate regression analysis revealed that the risk factor of NODAT was fasting plasma glucose pre-transplantation, HCV infection and systolic blood pressure.The independent determinant of the advanced arterial stiffness on NODAT was the statement of hypertension and age. Conclusions High fasting plasma glucose prior to transplantation, HCV infection and high blood pressure are risk factors for NODAT in patients after renal transplantation.Strict control of blood pressure is the key way to prevent the NODAT and atherosclerosis.
2.Transplantation of bone marrow-derived liver stem cells transfected with rat IL-10 gene for liver fibrosis in rats
Ning LAN ; Yuanwen CHEN ; Chao SUN ; Bowei LIU ; Qiaoling SUN ; Dingguo LI
Chinese Journal of Organ Transplantation 2009;30(7):403-406
Objective To explore the curative effectiveness of transplantation of bone marrow-derived liver stem cells (BDLSCs) transfected with rat interleukin-10 (IL-10) gene in the treatment of liver fibrosis in rats. Methods β2m-/Thy-1+BDLSCs isolated from Wistar rats were transfected with adenovirus-mediated rat IL-10 gene Wistar rats were subcutaneously injected with CCl4 to induce liver fibrosis, and randomly divided into three groups as follows: (1) the model group, infused with 1 ml normal saline (NS); (2) the BDLSC group, infused with NS containing untreated β2m-/Thy-1+BDLSCs (2×105 cells); (3) the IL-10 group, infused with NS containing β2m-/Thy-1+ BDLSCs transfected with IL-10 gene (2×105 cells). Infusion was done via the portal vein. Rats subcutaneously injected with olive oil served as control (the normal group). The BDLCs labeled with diamidine phenylindole dihydrochloride (DAPI) in the liver were localized. Pathological changes and collagen area in liver tissues were observed. Liver function and blood blotting function were tested. Results β2m-/Thy-1+ BDLSCs labeled with DAPI were observed in liver tissues of rats. Significant pathological changes of liver tissues were observed in the model group. Compared with the model group, pathological changes were alleviated to some extent in the BDLSC group. The morphology of liver tissue in the IL-10 group was mostly close to that in the normal group. Collagen deposition of liver tissues was increased obviously in the model group. However, transplantations of untreated and IL-10-transfected BDLSCs both reduced collagen area. Compared with the BDLSC group, collagen deposition was significantly suppressed in the IL-10 group. Transplantation of IL-10-transfected BDLSCs suppressed obviously the levels of ALT, AST, ALP, TBIL, PT and APTT as compared with the model group (P<0. 05). The levels of ALT, TBIL, PT and APTT in the IL-10 group were significantly reduced to the normal levels as compared with those in the BDLSC group (P<0. 05).Conclusions Transplantation of BDLSCs transfected with rat IL-10 gene was effective in treating liver fibrosis in rats. This combined strategy of IL-10 gene and BDLSCs may represent a feasible, effective and safe therapy form for liver fibrosis.
3.All-trans retinoic acid attenuates cardiac allograft vasculopathy and myocardial fibrosis
Mingkui ZHANG ; Qingyu WU ; Jianguo HU
Chinese Journal of Organ Transplantation 2009;30(7):394-397
Objective To investigate the mechanism of albtrans retinoic acid (atRA)attenuating cardiac allograft vasculopathy and myocardial fibrosis. Methods With inbred Wistar rats as donors and Sprague Dawley (SD) rats as recipients, heterotopic heart transplantation model was rejection group received same doses of cyclosporine A for 60 days. Grafts were removed on the day 60 post-transplant. Paraffin-embedded sections of cardiac allograft were stained with Masson's trichrome and Van Gieson for examination of myocardial fibrosis and vascular stenosis. Immunohistochemistry was performed to observe CD68 positive cell infiltration. Platelet-derived growth factor-A (PDGF-A)mRNA was detected by using reverse transcription-polymerase chain reaction (RT-PCR). Results The index of fibrosis in chronic rejection group and atRA-treated group was 64. 0 ± 11.9 and 34. 7 ±6. 3 respectively with the significant difference (P<0. 01). Chronic rejection all,grafts showed severe vessel disease. The luminal occlusion index of coronary arteries in chronic rejection group was 62. 9 4± 17. 2, and 40. 1± 8. 2 in atRA-treated group with significant difference (P<0. 01). CD68-positive cell count in atRA-treated group and chronic rejection group was 17. 6 4± 4. 2 and 32. 1 ± 9. 3 with significant difference (P<0. 01). The relative expression levels of PDGF-A mRNA in atRA-treated group and chronic rejection group were 0. 46 ± 0. 08 and 0. 94 4±0. 11 respectively with significant difference (P<0. 01). Conclusion AtRA attenuates cardiac all,graft vasculopathy and myocardial fibrosis. The effects might be induced by inhibition of CD68 positive cell infiltration and PDGF-A mRNA expression.
4.The efficacy and safety of sirolimus in immunosuppression after liver transplantation
Haibin ZHANG ; Yong FU ; Ning YANG ; Xin ZHANG ; Guangshun YANG
Chinese Journal of Organ Transplantation 2009;30(7):428-430
ObjectiveTo evaluate the efficacy and safety of Sirolimus (SRL) in immunosuppression following liver transplantation. Methods SRL was applied in 21 patients totally.Indication for adoption was Tac-related nephrotoxicity (4/21), suspiciously Tac-related hepatoxicity (8/21), Tac overdose (3/21), renal insufficiency pre-operation (2/21), or cancer (4/21). Median follow-up was 25. 4 months. Results SRL provided an adequate prophylaxis against rejection in all study patients, with one case of acute rejection. Sirolimus was Withdrawn in 2 cases due to its sideeffect. Tat-induced hepatoxicity in 6 cases and nephrotoxicity in 3 cases were relieved significantly.Conclusions SRL given alone appears to be an effective primary immunosuppressant regimen fororthotopic liver transplantation patients. Early conversion contributes to significant improvement of Tac-related hepatoxicity and nephrotoxicity.
5.The role of multi-detector row CT in evaluation or living renal donors
Jiqing ZHANG ; Xiaopeng HU ; Xi YIN ; Tao HUANG ; Liang REN ; Hang YIN ; Wei WANG ; Yong WANG ; Xiaodong ZHANG
Chinese Journal of Organ Transplantation 2009;30(7):419-421
Objective To assess the role of muhi-detector row CT (MDCT) in preoperative evaluation of living renal donors. Methods The data of 104 potential donors who underwent MDCT were retrospectively analyzed. All the candidates underwent 64-MDCT examination. First,unenhanced scans were performed on the kidneys. After administration of Ⅳ contrast medium,enhanced CT images of the arterial phase, venous phase, and excretory phase were obtained. The enhanced scan scope was from the top of diaphragmatic muscle to pubic symphysis. The scanning data obtained was post-processed for reconstructed images. The anatomy and variations displayed in MDCT images on kidneys, ureters, arteries and veins were recorded. The findings in surgery constituted the standard of reference for imaging findings, and the recorded results from images were compared with the findings in surgery to assess the role of MDCT in evaluation of potential donors. Results MDCT examination was successfully performed on 104 candidates. Anomalies of kidneys and ureters were found in 8 donors before surgery. The prevalence of accessory arteries and early branching in image was 27. 2 % (28/103) and 12. 6 % (13/103) respectively. There were 3 candidates with double veins and 3 with retroaortie left renal vein found in preoperative assessment. Ninety-three candidates underwent successful donor nephreetomy. The anomalies and variations of kidneys and ureters in images were all confirmed surgically. The detection rate of the accessory renal artery (ARA) was 80 %. The ARAs measuring > 1 mm in diameter and early branching were all detected by MDCT.The findings of veins found in performed sides coincided with those of MDCT images. Conclusion MDCT can accurately assess the anatomic information and variations of the donors' kidneys, and facilitate triaging donors and planning operation proposal
6.Gene and protein expression of protease-activated receptor-1, 2 in a routine model of acute graft-versus-host disease
Quan LI ; Jian ZHANG ; Ping ZOU ; Weiming LI
Chinese Journal of Organ Transplantation 2009;30(7):407-410
Objective To explore the expression of protease-aetivated receptor (PAR)-1, 2 in a routine model of acute graft-versus-host disease (aGVHD). Methods A routine model of aGVHD after aUogeneic hematopoietic stem cell transplantation (allo-HSCT) was established, and the syngeneic HSCT mice were used as the controls. Quantitative real-time PCR, Western blot and immunohistoehemistry were done to detect the gene and protein expression of PAR-1, 2 in multiple organs of allo-HSCT mice and the controls. Results Allo-HSCT mice showed classical symptoms and histological changes of aGVHD. PAR-1 mRNA expression was significantly increased in the skin,liver, small intestine of allo-HSCT mice (skin: 0. 039 ± 0. 013 vs. controls: 0. 008 ± 0. 002,P<0. 01 liver: 0. 165 ± 0. 084, vs. controls: 0. 017 ± 0. 006, P<0. 01 ; small intestine: 0. 215 ± 0. 109 vs.controls: 0. 016±0. 009, P<0. 01), but not in the stomach, lung and kidney of allo-HSCT mice (P >0. 05). PAR-2 mRNA expression in the liver and small intestine of allo-HSCT mice was significantly elevated (liver: 0. 010 ± 0. 003 vs. controls: 0. 003 ± 0. 002, P<0. 01 ; small intestine:0. 006 ± 0. 002 vs. controls: 0. 003± 0. 002,P<0. 05), but not in the other organs (P>0. 05). The protein expression of PAR-1, 2 was in accordance with the mRNA expression. Immunohistochemistry revealed the PAR-1, 2 expression was increased in the epithelial eeUs and vascular endothelial cells of target organs of aGVHD. Conclusion Inereased expression of PAR-1, 2 in the target organs of aGVHD suggests PAR-1, 2 may contribute to the pathogenesis of aGVHD after allo-HSCT.
7.The effect of splenectomy on peripheral lymphocyte apoptosis and CD4+ CD25+ Treg cells in rat with heart transplantation
Chinese Journal of Organ Transplantation 2009;30(3):133-136
Objective To investigate the effect of splenectomy on peripheral lymphocyte apoptosis and CD4+ CD25+ Treg cells in rat with heart transplantation. Methods Abdominal heterotopic heart transplantation was performed from Wistar (donors) to SD (recipients) rats. Splenectomy was done at the same time in recipients (heart graft splenectomy group), non-splenectomy recipients (heart graft group), single splenectomy in SD rats (spleneetomy group), and SD rats (no operation) were designed as the control group. The transplanted hearts and peripheral blood in each group were collected on the 1st, 3rd, 5th and 7th day after operation. Histopathological and ultrastructural changes in transplanted hearts were observed by microscope and electronic microscope. Apoptosis rate of peripheral lymphocytes and CD4+ CD25+ Treg cells were measured by flow cytometry. The expression of Foxp3 mRNA in CD4+ CD25+ Treg cells was detected by RT-PCR, and survival time of the transplanted hearts was recorded. Results The survival time of the transplanted hearts in heart graft splenectomy group was 17.63±4.54 days, significantly longer than that in heart graft group (7.47±2.24 days) (P<0.05). The transplanted hearts in heart graft group were swelling, hard, dark, with interstitial edema, hemorrhage, diffuse infiltration of inflammatory cells, necrosis and cytolysis of a lot of myocardial cells, blurred cross striations; The transplanted hearts in heart graft splenectomy group were soft, red, partially gray white, with focal edema of subepicardial cells,infiltration of inflammatory cells, intact myocardial cell structure, and clear cross striations; Compared to heart graft group, the ultrastructural changes of transplanted hearts in heart graft splenectomy group were lighter significantly. On the 5th and 7th day after operation, apoptosis of peripheral lymphocytes in heart graft splenectomy group was (7.62±2.15)% and (9.41±3.82)% respectively, significantly higher than in heart graft group (both P<0.05). On the 3rd, 5 th and 7th day after operation, the number of CD4+ CD25+ Treg cells in heart graft splenectomy group was more (all P<0.01), and the expression level of Foxp3 mRNA higher than in heart graft group. Conclusion Splenectomy can increase apoptosis rate of peripheral blood lymphocytes and the number of regulatory T lymphocytes, and up-regulate the Foxp3 mRNA regulation in rats with heart transplantation, which has a negative correlation with pathological changes of transplanted hearts.
8.The detection of cytokines in porcine-human mixed lymphocyte culture
Chinese Journal of Organ Transplantation 1997;18(3):158-160
In order to explore the relationship between xenograft rejection and cytokines, the proliferative responses and cytokine contents from human lymphocyte were detected in porcinehuman mixed lymphocyte culture (MLC) and compared with human allo-MLC. The results showed that the proliferative responses in the former was equal to or stronger than that in the latter, and the kinetics of IL-2 and IFN-Y in both supernatants were similar but the peak of IL-4 from the former was higher than that from the latter (P<0.05). This suggests that cytokines are likely to play roles in porcine-human MLC.
9.Effect of hemodialysis and renal transplantation on autonomic dysfunction in uremia
Chinese Journal of Organ Transplantation 1997;18(2):116-117
Autonomic functions were evaluated in 64 long-lerm maintenance hemodialysis patients,11 cases before and after transplantation and 15 controls.The results showed that adequate dialysis could stop the development of autonomic dysfunction (AD) in uremic patients,but the effect in improving AD was limited and not related to the duration of hemodialysis.Renal transplantation could reverse AD and result in complete normalization of autonomic function.
10.A preliminary study on the role of serum tumor necrosis factor alpha levels for diagnosis of early acute rejection after heterototpic rat heart-lung transplantation
Chinese Journal of Organ Transplantation 1996;17(1):18-20
In this study an acute rejecting model of heterotopic rat heart-lung transplantation was established by using simplified technique of end to side anastomosis of donor ascending aorta with recipient abdominal aorta.The measurements of tumor necrosis factor alpha(TNF-α)in serum of rats by Sandwich-ELISA method were taken on the 3rd,5th,7th days respectively after operation.The results of this study with histological examination showed that TNF-α serum levels were increased during acute rejection episodes.and it might be a useful indicator for diagnosis of allograft rejection.