去甲泽拉木醛在大鼠肾移植模型中免疫抑制作用的研究

发布时间：2018-01-11 00:14

本文关键词：去甲泽拉木醛在大鼠肾移植模型中免疫抑制作用的研究　出处：《复旦大学》2013年硕士论文　论文类型：学位论文

【摘要】：目的：为了更好地进行移植免疫机理的探讨、肾移植治疗的研究和筛选新型的免疫抑制剂,探索建立更理想的大鼠原位肾移植模型。材料与方法：用重250g、雄性SD和Wistar大鼠各10只作为肾移植的供、受体。暴露供体大鼠的左肾,在手术显微镜下解剖游离左肾动静脉、输尿管,阻断左肾血管的上下腹主动脉,经腹主动脉对左肾灌注0～4℃的肾保存液15～20ml,切取左肾、全长输尿管带部分膀胱瓣,修肾备用。切除受体左肾,用11—0显微缝合线间断端端吻合肾动脉,连续端端吻合肾静脉,8—0线缝合带膀胱瓣的输尿管于受体膀胱。切除右肾。术后每日环孢素(Cyclosporin A, CSA)10mg/kg.d灌胃,大鼠移植术后7天,经右眼内眦静脉抽血检查肾功能并取存活鼠的移植肾作病理检查。结果：术后七天有8只大鼠存活,成功率80%,在术后第七天,大鼠的血肌酐、BUN正常范围,与术前的血肌酐、BUN比较,P0.05,差别无显著性。术后七天移植肾病理显示肾组织少量淋巴细胞浸润,肾小球、肾小管及微血管完好。结论：在手术显微镜下建立大鼠左肾原位肾移植模型,能达到肾功能正常的要求,手术成功率较高,是可靠的大鼠移植模型。目的：CSA是目前器官移植后最常用的免疫抑制剂之一,而雷公藤红素是第一个从雷公藤中提取的单体。本试验以CSA和雷公藤红素作为对照,观察肾移植大鼠的生存期,观察去甲泽拉木醛(T-96)对免疫抑制的实用价值。材料与方法：以雄性SD、Wistar大鼠为供、受体,建立大鼠肾移植模型,依次进入对照组和各实验组,每组8只,另外实验组每组多准备2只,以备7天和14天时取移植肾送病理,不记入试验组。各组分别给予生理盐水,CSA5mg/kg.d, CSA10mg/kg.d, T-9610mg/kg.d, T-9620mg/kg.d,雷公藤红素0.3mg/kg.d和0.6mg/kg.d,每天灌胃一次。观察记录各组大鼠的生存天数,取死亡鼠肾脏送病理检查。结果：去甲泽拉木醛能显著延长大鼠的存活时间,且存在剂量效应关系,低剂量和高剂量组生存时间分别为15.1±1.04d和21.4±2.61d,与对照组相比有显著性差异(P0.01)。其存活时间与CSA组相当,差别无显著性(P0.05)。雷公藤红素低剂量组与T-96和CSA组相当,但高剂量生存时间较短(P0.05)。在7天肾脏病理检查时,对照组见显著的排斥征象,而各给药组不明显。在14天移植肾病理检查时,对照组已无存活鼠,各低剂量组可见较为明显的排斥,如大量淋巴细胞浸润,肾小管内大量蛋白尿,但肾小球仍较为完整。而T-9610mg/kg.d和CSA10mg/kg.d组仅可见少量淋巴细胞浸润,肾小球和小管、微血管完好。结论：本试验初步验证去甲泽拉木醛具有较强的免疫抑制作用,10mg/kg.d和20mg/kg.d均能显著的延长大鼠移植肾的存活时间,且有剂量效应关系,效果与CSA相仿。在高剂量,优于雷公藤红素。
[Abstract]:Objective: in order to better discuss the mechanism of transplantation immunization, we should research and screen new immunosuppressants for renal transplantation, and establish a more ideal orthotopic kidney transplantation model in rats.
Materials and methods: 250g male SD Wistar rats and 10 rats as renal transplantation for receptor. Exposure of left kidney donor rats, dissected the left renal artery and vein under surgical microscope ureteral occlusion of the left renal vessels, the abdominal aorta, abdominal aorta of left renal perfusion 0 to 4 DEG C kidney preservation solution 15 ~ 20ml, cut the left kidney and ureter with bladder flap, repair the renal reserve. The recipient's left kidney, with 11 - 0 suture line continuous end-to-end anastomosis of renal artery, continuous end-to-end anastomosis of renal vein, 8 - 0 line suture zone of the ureter to the bladder flap the recipient bladder. Resection of the right kidney. Postoperative daily cyclosporine (Cyclosporin A, CSA 10mg/kg.d) by gavage for 7 days, rats after transplantation, renal transplantation by right angular vein blood tests of renal function and survival of rats for pathological examination.
Results: seven days after the operation, 8 rats survived, the success rate of 80%, on the seventh day after operation, serum creatinine of rats, BUN in the normal range, and serum creatinine, preoperative BUN, P0.05, there was no significant difference. After seven days of transplant renal pathology of renal tissue showed that a small amount of lymphocyte infiltration. Glomerular, tubular and microvascular integrity.
Conclusion: a rat orthotopic renal transplantation model of left kidney can be established under operation microscope to achieve normal renal function and high success rate. It is a reliable rat transplantation model.
Objective: CSA is the most commonly used after organ transplantation and immunosuppression of tripterine is the first monomer extracted from Tripterygium wilfordii. In this experiment, CSA and tripterine as control rats, the survival of renal transplantation, to observe demethylzeylasteral (T-96) on immune suppression of practical value.
Materials and methods: male SD and Wistar rats as donors, receptor, rat kidney transplant model, in order to enter the control group and the experimental group, 8 rats in each group, the experiment group had to prepare more than 2 only, for 7 days and 14 days after transplantation of kidney pathology in experimental group. Each group respectively treated with normal saline, CSA5mg/kg.d, CSA10mg/kg.d, T-9610mg/kg.d, T-9620mg/kg.d, 0.3mg/kg.d and 0.6mg/kg.d of tripterine, orally once a day. The rats were recorded. The survival days of death from renal pathologic examination.
Results: demethylzeylasteral can significantly prolong the survival time of rats, and there was a dose effect relationship, low dose and high dose group survival time were 15.1 + 1.04d and 21.4 + 2.61d, compared with the control group there were significant differences (P0.01). The survival time and CSA group, no significant difference (P0.05). The celastrol and T-96 low dose group and CSA group, but high dose short survival time (P0.05). On the 7 day of renal biopsy, the control group saw significant signs of rejection, and each group is not obvious. On the 14 day of pathological examination, the control group has no survival in the low dose group showed obvious rejection, such as a large number of lymphocytic infiltration, renal tubular proteinuria, but still relatively complete. Glomerular T-9610mg/kg.d and CSA10mg/kg.d groups only showed a small lymphocytic infiltration, glomerular and tubular, microvascular intact.
Conclusion: this experiment demethylzeylasteral can inhibit the immune, 10mg/kg.d and 20mg/kg.d can significantly prolong the allograft survival time of rats, and the dose effect relationship, and the effect is similar to CSA. In high doses, better than tripterine.

【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R699.2;R-332

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