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目的探讨金雀异黄素(Gen,5,7,4’-三羟异黄酮,又称染料木黄酮)对糖尿病 (DM)大鼠肾组织系膜细胞(MC)表型和细胞外基质的作用。方法雄性SD大鼠45只,分为(1) 正常对照组:10只,普通鼠饲料自由饮食;(2)DM组:再分为4周组9只,8周组8只,普通鼠饲料自由饮食;(3)DM+Gen灌胃组:同样再分为4周组10只,8周组8只,普通鼠饲料自由饮食及 Gen 30 mg．kg-1·d-1。于实验4周、8周末禁食12 h,检测空腹血糖(FBG)、BUN、Scr,肾组织非肌肉型肌球蛋白重链(SMemb)mRNA表达、纤连蛋白(Fn)／肾重及基质金属蛋白酶(MMP)-2／组织基质金属蛋白酶抑制剂(TIMP)-I沉积结果。结果 DM大鼠FBG、BUN、Scr、Fn／肾重均高于正常对照组,以8周时最为显著(P<0．01);MMP-2／TIMP-1免疫组化半定量比值显著降低(P< O．01);SMemb mRNA／GAPDH mRNA半定量比值高于正常对照组,于4周达高峰,8周时下降 (0．794±0．037比0．708±0．029)。Gen干预后与同期DM组相比,肾功能部分恢复,SMemb mRNA／ GAPDH mRNA比值明显缩小(P<0．01);Fn／肾重也显著低于DM组(P<0．01);MMP-2／TIMP-1 比值与同期DM组相比也有显著增加(分别P<0．01或<0．05)。结论金雀异黄素可以减轻链脲佐菌素所诱导DM大鼠的肾皮质SMemb的表达,提高MMP-2／TIMP-1比值,改善糖尿病模型大鼠肾功能,可能有延缓糖尿病肾病(DN)进展的作用。
Objective To investigate the effects of genistein (Gen, 5,7,4’-Genistein, also known as genistein) on the phenotype and extracellular matrix of renal mesangial cells (MC) in diabetic rats. effect. Methods Forty-five male Sprague-Dawley rats were divided into (1) normal control group: 10 rats, and normal rats fed a diet-free diet; (2) DM group: 9 rats were divided into 4 weeks group, 8 rats in 8 weeks group. Free diet; (3) DM+Gen intragastric administration group: equally divided into 4 weeks group 10, 8 weeks group 8, common rats feed free diet and Gen 30 mg. Kg-1·d-1. After fasting for 12 h at the 4th and 8th week of the experiment, fasting blood glucose (FBG), BUN, Scr, non-muscle myosin heavy chain (SMemb) mRNA expression, fibronectin (Fn)/kidney weight, and matrix were detected in the kidney tissue. Results of metalloproteinase (MMP)-2/tissue matrix metalloproteinase inhibitor (TIMP)-I deposition. Results The FBG, BUN, Scr, Fn/kidney weights in DM rats were higher than those in the normal control group, with the most significant at 8 weeks (P<0.01). The semi-quantitative ratio of MMP-2/TIMP-1 immunohistochemistry was significantly decreased. (P < O.01); The semi-quantitative ratio of SMemb mRNA/GAPDH mRNA was higher than that in the normal control group, peaked at 4 weeks and decreased at 8 weeks (0.794 ± 0.037 vs. 0.708 ± 0.029). After Gen intervention, compared with DM group, renal function partially recovered, SMemb mRNA/GAPDH mRNA ratio decreased significantly (P<0.01), and Fn/kidney weight was significantly lower than DM group (P<0.01); The ratio of /2/TIMP-1 was also significantly increased compared with the DM group in the same period (P<0.01 or <0.05, respectively). Conclusion Genistein can reduce the expression of SMemb in renal cortex of DM rats induced by streptozotocin, increase the ratio of MMP-2/TIMP-1, improve the renal function of diabetic rats, and may delay the development of diabetic nephropathy (DN). ) The role of progress.