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目的:观察去甲斑蝥素(NCTD)对链脲佐菌素(STZ)诱导的糖尿病(DM)模型大鼠肾小球纤维粘连蛋白以及钙调磷酸酶表达的影响,探讨去甲斑蝥素抗肾小球纤维化的机制。方法:10只大鼠正常饮食为正常对照组(C)组,30只大鼠给予高脂高糖饮食+链脲佐菌素(STZ)制备DM模型,随机分3组:DM模型(D)组10只,小剂量去甲斑蝥素治疗(N1)组10只,大剂量去甲斑蝥素治疗(N2)组10只,给药8周后检测血糖,血肌酐水平变化;用免疫组化法检测肾组织肾小球纤维粘连蛋白(fibronectin,FN)以及钙调磷酸酶(calcineurin,CaN)表达,分别用realtime-PCR以及western blot法检测肾组织FN以及CaNmRNA和蛋白水平的表达。结果:模型(D)组血糖,血肌酐水平上升(P<0.05),同时肾小球区FN,CaN的表达高于正常(C)组(P<0.05)。去甲斑蝥素干预(N)组与模型组比较,去甲斑蝥素组肾小球区FN,CaN表达下调(P<0.05)。大剂量组效果更显著(P<0.05)。去甲斑蝥素(N)治疗组血糖水平,肾功能较(D)组无明显变化。结论:去甲斑蝥素能减少糖尿病大鼠肾小球区FN的表达,其作用机制可能是通过使CaN的表达下调而实现。
Objective: To observe the effect of norcantharidin (NCTD) on the expression of glomerular fibronectin and calcineurin in streptozotocin (STZ) -induced diabetic (DM) model rats and to explore the effect of norcantharidin The mechanism of pellet fibrosis. Methods: The normal diet of 10 rats was in normal control group (C), 30 rats were given high fat and high glucose diet + streptozotocin (STZ) to prepare DM model. The rats were randomly divided into 3 groups: DM model (D) Group (n = 10), low-dose norcantharidin (n = 10), high-dose norcantharidin (n = 10) and blood glucose and serum creatinine The expression of FN and calcineurin (CaN) in renal tissue was measured. The expression of FN and CaN mRNA and protein in renal tissues were detected by realtime-PCR and western blot respectively. Results: The level of blood glucose and serum creatinine in model group (D) increased (P <0.05), and the expression of FN and CaN in glomeruli was higher than that in normal group (P <0.05). Compared with model group, the expression of FN and CaN in glomeruli of norcantharidin group was decreased (P <0.05). High-dose group effect is more significant (P <0.05). Norcantharidin (N) treatment group, blood glucose levels, renal function than (D) no significant change. CONCLUSION: Norcantharidin can reduce the expression of FN in the glomeruli of diabetic rats. The mechanism may be through the down-regulation of CaN expression.