PSS对2型糖尿病大鼠肾小球基底膜改变的影响

Influence of PSS on glomerular capillary basement membrane in rat model of type 2 diabetes

目的观察藻酸双酯钠(PSS)对2型糖尿病大鼠肾小球毛细血管基底膜(GBM)改变的影响。方法高糖高脂饮食加小剂量链脲佐菌素(STZ)20mg·kg-1制作2型糖尿病动物模型,将实验动物分为正常对照组、糖尿病非干预组、PSS治疗组、洛伐他汀对照组,给药8wk后检测各组大鼠的血糖,肌酐清除率(Ccr),尿白蛋白排泄率(UAER)及肾脏肥大指数的变化,免疫组化检测肾小球内TGF-β1、Ⅳ型胶原(CⅣ)表达水平,电镜下观察GBM厚度的改变。结果病程8wk时各组糖尿病鼠UAER明显增加,肾小球TGF-β1、CⅣ表达增多,肾脏肥大指数、GBM厚度均增加。PSS治疗组的血糖值较糖尿病非干预组有所降低(P<0.01),TGF-β1、CⅣ表达降低(P<0.01),GBM增厚程度明显改善(P<0.05),UAER降低(P<0.05),而两组的Ccr并无明显区别,肾脏肥大指数轻微改变无统计学意义。结论早期应用PSS对糖尿病大鼠肾脏有保护作用,其作用机制可能是通过降低血糖,调节肾小球TGF-β1、CⅣ表达,抑制GBM增厚,从而改善DM模型大鼠肾脏超微结构,保护肾小球滤过屏障功能。

Aim To observe effects of PSS(polysaccharide)on glomerular capillary basement membrane(GBM) in type 2 diabetic rats. Methods Type 2 diabetic animal model was established by high-sugar and high-fat diets, associating injection of small count streptozotocin(STZ 20 mg·kg-1,iv). Adult male wistar rats were divided into four groups: normal control rats, non-treated diabetic rats and diabetic ratstreated with PSS ( 180 mg·kg-1·d-1), diabetic rats treated with Lovastatin. Plasma glucose, Creatinine clearance rate(Ccr), 24 h UAER, and profile of kidney hypertrophy were observed after 8 weeks. Protein expressions of TGF-β1 and CⅣ in renal were measured by immunohistochemistry. Renal tissues were analyzed by electron microscope. Results After 8 weeks, levels of UAER, profile of kidney hypertrophy and the thickness of GBM were obviously increased in diabetic rats. TGF-β1 and CⅣ were obviously higher expressed in diabetic rats than normal rats. In PSS-treated group, blood glucose level was decreased slightly but significantly. Expressions of TGF-β1, CⅣ were significantly decreased in PSS-treated diabetic rats than those untreated (P<0.01). UAER, the thickness of GBM was significantly decreased in PSS-treated diabetic rats than that untreated (P<0.05). But Ccr and profile of kidney hypertrophy showed no significant differences between the diabetic group and PSS-treated group. Conclusion PSS has a favorable effect on renal function and morphology in diabetic rats, which may be due to decreasing blood glucose, expressions of TGF-β1 and CⅣ and inhibiting the thickness of GBM, and then protecting glomerular filtration barrier.