2型糖尿病大鼠肾脏相关细胞因子表达与足细胞损伤关系

目的 探讨转化生长因子β1（TGF-β1）、骨形态发生蛋白7（BMP-7）、结缔组织生长因子（CTGF）、nephrin在2型糖尿病肾病（DKD）大鼠肾脏组织表达变化，及其与肾脏足细胞损伤的关系。方法 雄性SD大鼠50只，随机分为正常对照组（NC组，20只）和模型组（DKD组，30只），DKD组给予高糖高脂饲料喂养8周建立2型糖尿病模型，建模成功后空腹状态下给予小剂量链脲佐菌素（STZ，30 mg/kg）一次性腹腔注射；NC组给予常规饲料喂养，腹腔注射等量枸橼酸缓冲液，继续喂养8周。于8周末检测两组24 h尿清蛋白（UAL）、空腹血糖（FBG）、血肌酐（Scr）、尿肌酐（Ucr），电镜观察肾小球足细胞超微结构的变化，光镜检测肾小球硬化指数（GSI），免疫组化、实时定量PCR检测肾组织nephrin、BMP-7、CTGF、TGF-β1的表达。结果 与NC组比较，DKD组大鼠UAL、GSI明显升高，肾小球足细胞nephrin、BMP-7表达下调，而CTGF及TGF-β1表达上调，差异均有显著性（t=3.20-41.17,P〈0.01）。光镜下观察，DKD组大鼠肾小球肥大，系膜细胞增生，细胞外基质增多。电镜下观察，DKD组大鼠肾脏足细胞肿胀，足突融合消失，足细胞损伤。结论 DKD 大鼠肾小球存在足细胞损害，其机制可能与 BMP-7 表达下调及 CTGF、TGF-β1 过度表达有关。

CORRELATION BETWEEN KIDNEY-RELATED CYTOKINES AND PODOCYTE DAMAGE IN TYPE 2 DIABETIC RATS

Objective To explore the expressions of transforming growth factor （TGF-β1）, bone morphogenetic protein-7 （BMP-7）, connective tissue growth factor （CTGF） and nephrin in type 2 diabetic （T2DM） rat kidneys and their association with podocyte damage injury. Methods Fifty SD rats were randomized to two groups as normal control group （n=20） and diabetic kidney disease group （DKD, n=30）. The rats in DKD were fed with high fat and high sugar diet for eight weeks to create a model of T2DM, and upon completion of the model, a single dose of streptozotocin （STZ, 30 mg？kg-1） was intraperitoneally injected; those in the control group were fed with routine diet and given intraperitoneal injection of citric acid buffer solution. After eight weeks, urinary albumin （UA）, fasting blood glucose （FBG）, serum creatinine （Scr）, and urine creatinine （Ucr） were detected, the ultrastructure of podocytes in kidney glomerulus was observed electron-microscopically, GSI were detected by optic microscope, and the expressions of nephrin, BMP-7, CTGF, and TGF-β1 were detected by immunohistochemistry and real-time PCR. Results Compared with the control group, the UAL and GSI in DKD group increased, and that of nephrin and BMP-7 down-regulated, and CTGF and TGF-β1 significantly up-regulated （t=3.20-41.17,P〈0.01）. Glomerular hypertrophy, mesangial cell proliferation and extracellular matrix accumulation were observed by light microscope in DKD group, and electron-microscopically, podocytes were tumefied and foot processes were fusioned and podocytes damaged. Conclusion Podocyte damage exists in kidney glomerulus of diabetic rats, which is related to down-regulation of BMP-7 expression and over-expressions of CTGF and TGF-β1.