替米沙坦对老年糖尿病大鼠足细胞黏附的保护作用  

Protection of telmisartan for podocyte adhesion in aging rats of diabetic nephropathy

作　　者：陈铖[1] 贾俊亚[1] 丁国华[1] 梁伟[1] 褚瑰丽[1] 朱吉莉[1] 贾汝汉[1] 

机构地区：[1]武汉大学人民医院肾内科,430060

出　　处：《中华肾脏病杂志》2007年第3期172-177,共6页Chinese Journal of Nephrology

基　　金：国家自然科学基金（30370656）;国家教育部留学回国人员科研启动基金（2000367）;湖北省卫生厅重点科研项目（JXIB011）

摘　　要：目的 探讨替米沙坦对足细胞黏附的保护作用。方法 用20月龄SD大鼠制备糖尿病模型，随机分为糖尿病组和替米沙坦治疗组，另设老年和6周龄对照组。于实验第4、8、12周末收集大鼠24h尿，监测血压。12周后行组织病理学检查，检测尿白蛋白（24h）和血、尿肌酐。以间接免疫荧光-hoechst33342双染检测尿中足细胞数量。RT—PCR、免疫组化和Western印迹等方法检测肾小球中整合素α3、整合素连接激酶（ILK）mRNA和蛋白表达。结果随实验进程，老年糖尿病大鼠尿白蛋白、血压和尿中足细胞数量明显高于对照组（P〈0．05），且出现较为明显的病理学损害。肾小球整合素α3mRNA及蛋白表达量减少，ILK表达明显增加（P〈0．05）。第12周，整合素α3蛋白表达与ILK表达呈负相关（P〈0．05）。尿足细胞数量、尿白蛋白程度与ILK表达呈正相关fP〈0．05）。替米沙坦明显减轻肾脏病理损害，增加整合素α3表达，降低ILK表达，减少尿足细胞数量。结论 老年糖尿病大鼠足细胞的黏附能力下降，尿足细胞排泄增加。替米沙坦可增强足细胞黏附，对足细胞存活起重要作用。Objective To evaluate the effects of telmisartan on expression of integrin α3 and integrin-linked kinase （ILK） in 20-month-old Sprague-Dawley rats by intraperitoneal injection of streptozotocin （STZ）. Methods STZ rats were treated with or without telmisartan for up to 12 weeks. 24-hour albuminuria, blood pressure and urinary podocytes were measured at weeks 4, 8 and 12,respectively. Animals were sacrificed at week 12. Serum and urinary creatinine were measured and kidney tissues were harvested. Expression of integrin α3 and ILK mRNA and protein in glomeruli was evaluated by RT-PCR, immunohistochemistry and Western-blot, respectively. Results STZ aging rats presented significant podocyte damage, albuminuria and excretion of urinary podocyte. Telmisartan reduced urinary podocytes and protected STZ aging rats from renal damage. Integrin α3 expression in STZ aging rat was markedly decreased （P 〈 0.05）, while expression of ILK was significantly increased. The level of ILK expression was negatively correlated with integrin α3 expression （r=-0.64, P 〈 0.05）and positively with urinary podocyte and albuminuria after 12 weeks （r=0.79 and 0.74, P 〈 0.05 respectively）. Telmisartan obviously extenuated STZ-associated reduction in integrin α3 and increasement in ILK （P 〈 0.05）. Conclusion The alterations in integrin α3 and ILK expression as well as the modulating effect of telmisartan are directly involved in the pathogenesis of podocyte injury.

关 键 词：糖尿病肾病 整合素Α3Β1 替米沙坦 足细胞 整合素连接激酶 老年 

分 类 号：R686[医药卫生—骨科学]