摘要目的 探讨雷公藤多苷(TWP)对糖尿病肾病大鼠尿蛋白、足细胞损伤及肾皮质nephrin 蛋白表达的影响.方法 建立高脂饮食联合链脲佐菌素诱导糖尿病肾病大鼠模型,随机分为糖尿病肾病模型组、小剂量TWP(6 mg·kg-1·d-1)治疗组及大剂量TWP(12 mg·kg-1·d-1)治疗组,并以正常大鼠为对照,每组12只.干预12周后检测大鼠24 h尿蛋白量、血肌酐及尿素氮水平,并以苏木素-伊红染色(HE)、过碘酸希夫染色(PAS)、Masson染色检测肾组织病理变化;透射电镜测量足细胞超微结构变化;免疫组化检测肾皮质nephrin蛋白表达.结果 与正常大鼠相比,2型糖尿病大鼠尿蛋白明显增加[( 3.28±0.26) mg/24 h vs.(27.60±0.24) mg/24 h],而小剂量及大剂量TWP治疗后大鼠尿蛋白均明显改善[分别为(12.63 ±0.21)及(10.50±0.15) mg/24 h,P＜0.05)],大剂量TWP治疗组尿蛋白低于小剂量TWP治疗组,但差异末达统计学意义.病理分析显示糖尿病肾病模型组表现为肾小球硬化、基底膜增厚,肾小管变形、上皮细胞空泡变性,间质纤维化,足细胞足突增宽、融合、细胞减少,TWP治疗组大鼠肾小球、小管间质及足细胞病变明显减轻.同时免疫组化结果显示TWP治疗使肾脏皮质nephrin蛋白表达增加,且大剂量TWP治疗组高于小剂量TWP治疗组.结论 TWP可能通过增加nephrin的表达,发挥其对糖尿病肾病足细胞功能的保护作用.

abstractsObjective To explore the effects of triperygium wilfordii polyglucoside (TWP) on proteinuria,podocytes damages,nephrin expression in rats with diabetic nephropathy.Methods Diabetic nephropathy was established in rats using high lipids diet combined with streptozotocin (STZ).Diabetic rats were randomized into diabetic nephropathy model,low dosage of TWP( 6 mg · kg- 1 · d-1) and high dosage of TWP( 12 mg · kg-1 · d-1 )group.Normal rats were used as control and 12 rats for each group.After intervention for 12 weeks,24 h urinary protein excretion rate (UAER),serum creatinine and plasma urea nitrogen were accessed.The pathological changes of kidney were evaluated by Haematoxylin and eosin( HE),Periodic acid schiff(PAS),Masson staining.Ultrastructural alteration was examined by transmission electron microscope.The expressions of nephrin were evaluated by immunohistochemical staining.Results Compared with normal rats [ ( 3.28 ± 0.26 ) mg/24 h ],macroalbuminuia increased in diabetic rats [ ( 27.60 ± 0.24 ) mg/24 h],whereas the level of urine protein significantly decreased in 6 and 12 mg · kg-1 · d-1 TWP treatment for 12 weeks[ ( 12.63 ±0.21 ) and( 10.50 ± 0.15 ) mg/24 h ].There was no significant statistical difference between high and low dose of TWP group( P ＜0.05 ).In renal pathologic examination of diabetic nephropathy model group,the glomerular were sclerosis,with thicker basement membranes,deformed renal tubules,vacuolar degenerated epithelial cells and sclerosed interstitial were observed.The foot processes of podocyte were widen and fused,and the number of podocyte was also decreased.However,the kidney and podocyte lesions were improved significantly both in high and low dose of TWP groups.The expressions of nephrin by immunohistochemistry were also increased in both TWP treatment groups,with more statistical improvement in high dose group.Conclusions TWP may exert its protective effect on podocytes function in diabetic nephropathy through increasing nephrin expression.