阿托伐他汀促进糖尿病大鼠肾组织BMP-7和SnoN的表达  

Atorvastatin promotes the expressions of bone morphology protein-7 and SnoN in the kidney of diabetic rats

作　　者：彭伟 张小欢 刘玲伶[1,2] 王圆圆 刘丽荣[2,3] 石明隽 郭兵[1,2] PENG Wei;ZHANG Xiao-huan;LIU Ling-ling;WANG Yuan-yuan;LIU Li-rong;SHI Ming-jun;GUO Bing(Dept.of Pathophysiology,School of Basic Medicine;Laboratory of Pathogenesis Research,Drug Prevention and Treatment of Major Diseases;Dept.of Clinical Hematology,School of Medical Diagnositics,Guizhou Medical University,Guiyang 550025,China)

机构地区：[1]贵州医科大学基础医学院病理生理学教研室,贵州贵阳550025 [2]贵州医科大学贵州省高校重大疾病发病机制及药物防治特色重点实验室,贵州贵阳550025 [3]贵州医科大学医学检验学院临床血液学教研室,贵州贵阳550025

出　　处：《基础医学与临床》2018年第10期1373-1377,共5页Basic and Clinical Medicine

基　　金：国家自然科学基金(81760131);教育部博导项目(2013521510001);贵州省科技厅联合基金[黔科合LH字【2015】7335]

摘　　要：目的观察阿托伐他汀(AT)治疗对糖尿病大鼠肾组织骨形态发生蛋白-7(BMP-7)和核转录共抑制因子SnoN表达的影响。方法将大鼠分为对照组(NC组)、糖尿病组(DM组)(用链脲佐菌素(STZ)复制糖尿病大鼠模型)和糖尿病+阿托伐他汀灌胃治疗组(AT组),每组n=8。16周后处死大鼠,检测生化指标,观察肾组织病理学改变,免疫组化检测肾组织胶原蛋白Ⅰ(ColⅠ)和胶原蛋白Ⅲ(ColⅢ)的表达,Western blot检测肾组织BMP-7、SnoN、E-钙黏蛋白(E-cadherin)、骨架蛋白(Desmin)和胶原蛋白Ⅳ(ColⅣ)的表达。结果与对照组相比,DM组大鼠的血糖、三酰甘油、肾脏指数、尿微量白蛋白/尿肌酐(MA/CR)均增多(P<0.05);AT组大鼠上述指标回降(P<0.05)。DM组出现了肾小球萎缩、肾小管炎性浸润等典型纤维化病变,AT组病变有所减轻。DM组ColⅠ和ColⅢ增多,AT组回降。与对照组相比,DM组BMP-7、SnoN、E-cadherin表达显著减少,而Desmin和ColⅣ表达增多;AT组BMP-7、SnoN、E-cadherin表达回升(P<0.05),而Desmin和ColⅣ表达回降(P<0.05)。结论阿托伐他汀可以通过上调BMP-7和SnoN的蛋白表达来治疗或延缓糖尿病肾病。Objective To observe the effects of atorvastatin on the expression of bone morphology protein- 7 and SnoN in the kidney of diabetic rats. Methods The rats were divided into normal control（NC） group,diabetic （DM） group and atorvastatin lavage（AT） group randomly.After 16 weeks,the rats were sacrificed to measure biochemical parameters,and to observe the changes of pathomorphology.Meanwhile,immunohistochemistry and Western blot were employed to examine protein expression of collagen-Ⅰ（Col-Ⅰ）, collagen-Ⅲ（Col-Ⅲ）, BMP- 7,SnoN, E-cadherin,Desmin and collagen-Ⅳ（Col-Ⅳ）in the renal tissue. Results Compared with NC group, the level of blood glucose（BG）, triglyceride（TG）, kidney index and the urine trace albumin/uric creatinine （MA/CR） were increased remarkably in DM group（ P 〈0.05）. In AT group,the levels of BG, TG, MA/CR were reduced（ P 〈0.05）. The glomerular atrophy was observed in the DM group as compared with the NC group, and the alleviated renal fibrosis was observed in AT group. Compared with NC group, the expression of BMP- 7, SnoN, E-cadherin were significantly decreased in DM group, the expression of Desmin, Col Ⅰ, Col Ⅲ and Col Ⅳ were a significantly increased in DM group（ P 〈0.05）. In vivo ,compared with DM group, Atorvastatin increased the expression of BMP- 7, SnoN and E-cadherin; the expression of Desmin,Col Ⅰ,Col Ⅲ and Col Ⅳ were a significantly decreased in AT group（ P 〈0.05）. Conclusions Atorvastatin promotes the expression of BMP- 7 and SnoN,therefore protect the kidney of diabetic rats.

关 键 词：糖尿病肾病 骨形态发生蛋白-7 SNON 

分 类 号：R363.1[医药卫生—病理学]