芪卫颗粒对自发性2型糖尿病KK-Ay小鼠肾组织转化生长因子β_1蛋白及mRNA表达的影响

Effects of Qiwei Granule on the Protein and mRNA Expressions of Renal Tissue Transforming Growth Factor-β1 in KK-Ay Mice with Spontaneous Type 2 Diabetes Millitus

目的探讨芪卫颗粒对KK-Ay小鼠肾组织TGF-β1蛋白及mRNA表达的影响。方法采用自发性2型糖尿病KK-Ay小鼠模型。将KK-Ay小鼠随机分为模型组、中药组、西药组,以C57BL/6J小鼠作为正常组,每组15只,连续治疗12周,用HE、PAS及Masson染色法观察肾脏病理改变。采用免疫组织化学法及实时荧光定量PCR法,检测肾组织中转化生长因子β1(TGF-β1)的蛋白及mRNA表达。结果模型组小鼠肾脏病理改变呈现肾小球肥大,系膜基质区增宽,系膜细胞增多,肾小管上皮细胞空泡样变性,肾小管扩张,灶状萎缩,偶见坏死,可见较多蛋白管型,间质内炎性细胞浸润,间质纤维化表现。肾脏细胞内的TGF-β1的蛋白及mRNA表达较正常组明显增多。经芪卫颗粒、缬沙坦处理后,小鼠肾脏病理改变较模型组明显减轻,TGF-β1的蛋白及mRNA表达明显降低(P<0.05)。结论芪卫颗粒可通过抑制TGF-β1的蛋白及mRNA表达起到防治糖尿病肾病的作用。

Objective To study the effects of Qiwei Granule （QWG） on the protein and mRNA expressions of renal tissue transforming growth factor β1 （TGF-β1） in KK-Ay mice with spontaneous type 2 diabetes milli- tus （T2DM）. Methods Spontaneous T2DM KK-Ay mice model was adopted. Forty-five male mice were ran- domly divided into three groups, i.e., the model group, the Chinese medicine group, and the Western medicine group, 15 in each group. Fifteen male C57BL/6J mice were set up as the normal control group. The mice in the Chinese medicine group and the Western medicine group were administered intragastrically with QWG （at the daily dose of 20 g/kg） and valsartan （at the daily dose of 10 mg/kg）, and the treatment lasted for 12 successive weeks. The pathological changes of the kidney were observed using HE staining, PAS, and Masson staining. The protein and mRNA expressions of TGF-β1 were detected using immunohistochemical method and Real-time fluorescent quantitative PCR. Results The renal pathological changes of mice in the model group showed hypertrophic glomeruli, widened mesenteric matrix, increased mesangial cells, vacuolar renal tubular epithelial cells, tubular ectasia, and foci atrophy. Necrosis was occasionally seen. More protein cast, mesenchymal infiltration of inflammatory cells, and interstitial fibrosis could be seen. The protein and mRNA expressions of TGF-β1 increased more in the model group than in the normal control group. After treatment by QWG and valsartan, the renal pathological changes were obviously alleviated, and the protein and mRNA expressions of TGF-β1 were obviously lowered （P 〈 0. 05）. Conclusion By inhibiting the protein and mRNA expressions of TGF-β1, QWG could play a role in preventing and curing diabetic nephropathy.