[关键词]
[摘要]
目的 探讨Wnt/β-catenin通路在糖尿病肾病(DN)大鼠肾脏的表达及化瘀通络中药对其的干预作用。方法 60只大鼠中选取10只为对照组,其余大鼠给予高糖高脂饲料喂养联合ip小剂量链脲佐菌素(STZ)制备DN模型。成模大鼠随机分为模型组、厄贝沙坦组、化瘀通络中药组,各组ig给药,20周末检测24 h尿蛋白定量,RT-PCR法检测Wnt4、β-catenin mRNA表达,免疫组化及Western blotting法检测Wnt4、β-catenin蛋白的表达。结果 与对照组比较,模型组大鼠24 h尿蛋白定量及Wnt4、β-catenin mRNA和蛋白的表达量明显升高(P<0.01)。与模型组比较,中药组及厄贝沙坦组24 h尿蛋白定量及Wnt4、β-catenin mRNA和蛋白的表达量明显降低(P<0.05、0.01)。结论 化瘀通络中药可减少DN大鼠尿蛋白,且能够抑制大鼠肾脏存在的Wnt/β-catenin通路高表达,该作用可能是其减少蛋白尿排泄的主要途径之一。
[Key word]
[Abstract]
Objective To investigate the expression of Wnt/β-catenin pathway in diabetic nephropathy (DN) rats and the intervention effect of Chinese materia medica (CMM) for dispersing blood stasis and dredging collateral. Methods Ten rats were selected as control group from 60 rats, the remaining rats were established as DN models by feeding high glucose and high fat diet combined with low-dose streptozotocin ip injection. Model rats were randomly divided into model group, irbesartan treatment group, and CMM group. The rats in each group were ig administered with corresponding drug, at the end of the 20th week, the 24 h urinary total protein was detected. The expression levels of Wnt4 and β-catenin mRNA and protein in renal tissue were detected. Results Compared with control group, the 24 h urinary total protein, expression of Wnt4, β-catenin mRNA, and protein significantly increased in the model group (P<0.01). Compared with model group, 24 h urinary total protein, the expression of Wnt4, β-catenin mRNA, and protein decreased significantly in irbesartan group and CMM group (P<0.01 or P<0.05). Conclusion CMM for dispersing blood stasis and dredging collateral might decrease proteinuria in DN rats. It can also inhibit the high expression of Wnt/β-catenin pathway in the kidney of diabetic nephropathy rats. The effect might be one of the main ways to reduce urinary protein excretion.
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[基金项目]
国家自然科学基金资助项目(81373804,81173419)