TRPC6在糖尿病肾脏疾病大鼠肾组织的表达及缬沙坦的作用  

Effect of valsartan on TRPC6 expression in kidney of rat diabetic model induced by streptozotocin

作　　者：肖厚勤[1] 费沛[1] 陈新河[1] 胡兆雄[1] 张永[1] 刘双信[2] 

机构地区：[1]湖北医药学院附属太和医院肾内科,十堰442000 [2]广州广东省人民医院肾内科,510080

出　　处：《临床肾脏病杂志》2013年第12期567-570,共4页Journal Of Clinical Nephrology

基　　金：湖北省自然基金重大项目（No.2010CDA037）;湖北省教育厅重点项目（No.D20102105）;十堰市太和医院博士启动项目（No.2010QD02）

摘　　要：目的观察瞬时受体阳离子通道6（transientreceptorpotentialcationchannel6，TRPC6）在糖尿病肾脏疾病（diabetickidneydisease，DKD）鼠肾组织的表达及缬沙坦的作用。方法通过单肾切除联合链脲佐菌素（streptozotocin，sTZ）诱导的DKD模型随机分为糖尿病组（diabetesmellitus，DM）和缬沙坦治疗组，每组10只。另以10只大鼠作对照组（normalcontrol，NC）。缬沙坦组每天给予缬沙坦20mg／kg于饮水中，于8周、16周、24周检测不同时间点24h尿蛋白、血肌酐和血糖。24周处死动物，PAS染色和透射电镜观察肾组织学改变，激光共聚焦检测TRPC6、synaptopodin的表达和分布，免疫组化、RT-PCR检测nephrin、TRPC6mRNA和蛋白的表达。结果与NC组比较，DM组24h尿蛋白、肾质量／体质量指数、TRPC6的表达均显著高于NC组（P〈O．01），而内生肌酐清除率（endogenouscreatinineclearancerate，Ccr）、nephrin的表达显著低于NC组（P〈0．01）。激光共聚焦显示TRPC6与足细胞标志蛋白synaptopodin高度融合，沿毛细血管袢线形分布。缬沙坦组24h尿蛋白、肾质量／体质量、TRPC6的表达较DM组显著降低，Ccr、nephrin免疫组化积分和mR-NA的表达显著增加，肾脏病理改变减轻。结论DKD大鼠足细胞TRPC6的表达显著升高，缬沙坦可能通过抑制TRPC6的表达来减轻足细胞的损伤。Objective To evaluate the effect of valsartan on transient receptor potential cation channel 6 （TRPC6） expression and distribution in kidney of rat diabetic model induced by streptozoto- cin （STZ）. Methods Twenty rats injected with STZ were randomly divided into diabetes mellitus （DM） group and valsartan group （ARB）. Ten normal rats served as control group （NC）. The rats in ARB group were administrated with valsartan in drinking water at a dosage of 20 g/kg for 24 weeks. Rats in other groups were treated with normal saline. Blood sugur and 24-h urinary protein and creati- nine were measured at 8th, 16th and 24th week respectively. Animals were scarificed at 24th week after STZ injection. The expression of TRPC6 and nephrin was examined by using laser confocal micro- scope, RT-PCR and immunohistochemistry respectively. Results As compared with NC group, 24-h u- rinary protein, ratio of kidney weight to body weight and TRPC6 expression were significantly in- creased,while creatinine clearance rate （Ccr） and nephrin expression were reduced in DM group （P〈 0. 01 for all）. Laser confocal microscopy revealed that TRPC6 fused closely with synaptopodin, and had a linear distribution along the capillary loops. In valsartan group, 24-h urinary protein excretion, ratio of kidney weight to body weight and TRPC6 expression were significantly reduced, Ccr and nephrin ex-pression were significantly increased, and the renal pathological changes were alleviated as compared with DM group. Conclusions TRPC6 expression was increased and nephrin expression was decreased in the podocytes of diabetic rats. Administration of valsartan can alleviate the damage to podocytes by down-regulating the TRPC6 expression.

关 键 词：足细胞 缬沙坦 大鼠 

分 类 号：R5[医药卫生—内科学]