不同时间输注骨髓间充质干细胞对大鼠肾脏缺血再灌注损伤的影响  

Protective effect of MSCs by distinct administration time on renal ischemia-reperfusion injury in rats

作　　者：邱月[1] 戚贵生 杨橙[1] 赵天[1] 许明[1] 薛寅佳[1] 赵梓彤[1] 林淼[1] 邱甬鄞 戎瑞明[1] 朱同玉 

机构地区：[1]复旦大学附属中山医院泌尿外科,上海200032 [2]上海市器官移植重点实验室

出　　处：《中华器官移植杂志》2012年第4期246-249,共4页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金面上项目（81070595）;国家自然科学基金（81100533）

摘　　要：目的观察不同时间输注骨髓间充质干细胞（MSC）对大鼠肾脏缺血再灌注损伤（IRI）的影响。方法以切除一侧肾脏夹闭对侧肾血管的方法制备肾IRI大鼠模型，3个实验组分别于恢复肾血流前2h（灌前组）、恢复肾血流即刻（即刻组）和恢复肾血流6h时（灌后组）经尾静脉注射经荧光染料标记的MSC2×10^6个，并设不输注MSC的对照组（IR组）和假手术对照组（假手术组）。观察输注Msc后6h肾组织中MSC的分布情况；检测再灌注后6、24和48h的血肌酐（Cr）和尿素氮（BUN）水平；观察再灌注后48h的肾组织病理改变和肾小管上皮细胞凋亡情况。结果输注MSC者均可在肾脏中观察到MSC，以灌后组最多（P〈0．05）。再灌注后24h和48h时，输注MSC者的血cr和BUN与假手术组比较，差异均无统计学意义（P〉0．05），但均明显低于IR组（P〈0．05）。与IR组比较，输注MSC者的。肾脏病理损伤减轻，细胞凋亡数减少，以灌后组的改善最为明显（P〈0．05）。结论输注MSC可减轻大鼠肾脏的IRI，这一效应在再灌注后输注MSC者最为明显，可能是通过减轻炎症反应和抑制肾小管细胞凋亡来减轻IRI。Objective To observe the protection and distribution of bone marrow mesenchymal stem cells （MSCs） by distinct intravenous infusion time on renal ischemia-reperfusion injury （IRI） in rats. Methods We used unilateral nephrectomy and contralateral vascular occlusion method to establish renal IRI model in rats. The experimental groups which received 2 ×10^6 MSCs infusion through the tail vein, were subsequently divided into 3 subgroups： 2-h pre-reperfusion （PreOp, n = 16）, immediately after reperfusion （Op, n = 16）, 6 h post reperfusion （PostOp, n= 16）. The control groups included sham operation group （n = 16） and isehemia group （n= 16）. Chemotaxis of DAPI- labeled MSCs was detected 6 h after administration in the IR kidney. Renal function was detected at 6, 24, and 48 h respectively after operation. Forty-eight h after operation, the renal tissues were harvested to observe the pathological changes by HE staining and the tubular epithelial cell apoptosis via TUNEL assay. Results MSCs were found in the experimental groups after IR in the kidney, most in PostOp group. Twentyfour and 48 h after reperfusion, there was no significant difference in Cr and BUN between the experimental groups and sham operation group （P〉0.05）, but the levels of Cr and BUN in the experimental groups were significantly lower than in the IR group （P〈0. 05）. As compared with IR group, the renal pathological injury was alleviated, the number of apoptotic cells was decreased in the experimental group, most significantly in PostOp group （P〈0. 05）. Conclusion MSCs can reduce the inflammatory response and inhibit renal tubular cell apoptosis in rat renal IRL Post-reperfusion administration of MSCs leads to the best chemotaxis efficiency and protection.

关 键 词：大鼠 骨髓 间质干细胞 肾 再灌注损伤 

分 类 号：R285.5[医药卫生—中药学]