雷公藤多苷对糖尿病大鼠肾小球足细胞病变的保护作用  

Protective effects of Triptergium Wilfordii Polyglycosideson on podocyte lesions of rats with diabetic nephropathy

作　　者：凌厉[1] 陈立波[1] 劳国娟[2] 张长宁[1] 林刁珠[2] 

机构地区：[1]广东医学院附属深圳南山医院内分泌科,广东省深圳518052 [2]中山大学孙逸仙纪念医院内分泌科

出　　处：《中国慢性病预防与控制》2016年第7期489-492,共4页Chinese Journal of Prevention and Control of Chronic Diseases

基　　金：国家自然科学基金青年科学基金项目(81400818);2014年度深圳市卫生计生系统科研项目(201402128)

摘　　要：目的探讨雷公藤多苷(TWP)对糖尿病肾病(DN)大鼠足细胞病变及肾皮质nephrin蛋白表达的影响,为糖尿病的治疗提供实验依据。方法建立高脂饮食联合链脲佐菌素(STZ)诱导DN大鼠模型,按随机数字表法分为DN组13只,小剂量TWP组(每天8 mg/kg)13只和大剂量TWP组(每天16 mg/kg)14只,并以正常大鼠为对照组(n=15)。干预12周后检测大鼠24 h尿蛋白量、血肌酐值(SCr)、尿素氮(BUN)、血糖(Glu)、肾质量/体质量的变化,并以光学显微镜及电子显微镜观察肾脏组织病理改变;免疫荧光法检测肾皮质nephrin蛋白表达。用SPSS 13.0统计软件进行单因素方差分析。结果与对照组大鼠[(0.06±0.02)mg]比较,DN组大鼠24 h尿蛋白[(1.87±0.12)mg]明显增加,差异有统计学意义(P<0.01),TWP干预可显著减少糖尿病大鼠尿蛋白排泄,小剂量和大剂量TWP组尿蛋白分别为(0.98±0.21)、(0.33±0.11)mg,与DN组比较,差异均有统计学意义(P<0.05),此效应与TWP干预剂量相关,大剂量TWP组尿蛋白较小剂量TWP组下降更明显,差异统计学意义(P<0.05)。病理结果显示,DN组表现为肾小球体积增大,基底膜增厚,系膜基质显著增多,足细胞足突增宽、融合、细胞减少;TWP组大鼠肾小球、小管间质及足细胞病变明显减轻。免疫组化结果显示,DN组大鼠肾脏皮质nephrin蛋白表达[每个肾小球平均(2.35±1.75)个]较对照组大鼠肾脏皮质nephrin蛋白表达[每个肾小球平均(18.24±2.89)个]明显减少,差异有统计学意义(P<0.01),而TWP组大鼠肾脏皮质nephrin蛋白表达增加,差异有统计学意义(P<0.01),且小剂量TWP组[每个肾小球平均(11.34±1.56)个]与大剂量TWP组[每个肾小球平均(15.27±2.03)个]的差异有统计学意义(P<0.05)。结论 TWP干预可缓解DN大鼠足细胞病变,肾皮质nephrin蛋白表达上调可能在该保护机制中发挥作用。Objective To explore the effects of Triptergium Wilfordii Polyglycosides （TWP） ou podoeyte lesions and renal cortical nephrin protein level of rats with diabetic nephropathy （DN）, and to provide the experimental basis for the treatment of diabetes. Methods The DN rat model was induced by high-fat diet combined with streptozotocin （STZ）, and the model rats were divided into DN group （n=13）, low-dose TWP group （8 mg/kg each day, n=13）, and high-close TWP group （16 mg/kg each day, n=14） using the random number table method, the normal rats served as control group （n=15）. After intervention for 12 weeks, the changes of 24 h urine protein level, blood ereatinine （SCr）, blood urea nitrogen （BUN）, blood glucose （Glu）, and kidney mass/ body mass were detected; the pathological changes of kidney tissue was observed under the optical and electron microscopes; the nephrin protein expression of renal cortex was determined by immunofluorescence assay. SPSS 13.0 software was used to analyze the data. Results Urine protein level （1.87＋0.12 rag） of DN group was significantly higher than t.hat （0.06＋0.02 rag） of control group （P〈0.01）. TWP intervention could significantly reduce the urine protein excretion of diabetic rats, the urine protein levels of low TWP group and high TWP group were （0.98＋0.21） and （0.33＋0.11 ） rag, respectively, which were significantly lower than that of DN group （P〈0.05）, also there was the significant difference of urine protein level between low TWP group and high TWP group （P〈0.05）. Pathological results showed that the glomerular sclerosis, basement membrane thickening, renal tubular defomnation, epithelial cell vacuolization deformation, and interstitial fibrosis as well as broadening or fusion of podoeytic foot processes and reduction of podocytes appeared in DN group. The glomerular, tubular interstitial and podocytic lesions of TWP group were significantly improved. ImmunohistochemistU results showed that the nephrin

关 键 词：糖尿病肾病 雷公藤多苷 足细胞 nephrin蛋白 

分 类 号：R587.1[医药卫生—内分泌]