银杏叶提取物对糖尿病肾病的防治作用与机制研究

Preventive and curative effects of Ginkgo biloba extract on diabetic nephropathy

目的:观察银杏叶提取物(GBE)对糖尿病肾病大鼠核转录因子κB(NFκB)活性、肿瘤坏死因子α(TNFα)和白细胞介素6(IL 6)水平的影响,探讨其对糖尿病肾病的防治作用及其机制。方法:22只W istar大鼠分为正常对照组(A组),糖尿病无干预组(B组),GBE干预组(C组)。以一次性腹腔注射链脲佐菌素60 m g/kg制备糖尿病大鼠模型。12周后取肾组织进行病理学观察,以电泳迁移率变动分析法检测肾组织NFκB活性,放射免疫法测定血清TNFα和IL 6水平。结果:B、C组大鼠饲养过程中各死亡2只,存活大鼠空腹血糖>13.9 mm o l/L,模型制作成功。B组肾小球基底膜厚度、肾小球内细胞数和单个核细胞数显著多于A组,C组显著少于B组而多于A组(P均<0.05)。与A组比较,B组肾组织NFκB活性、TNFα和IL 6水平均显著升高,C组也有升高但明显低于B组(P均<0.05)。TNFα、IL 6水平与NFκB活性呈正相关(r1=0.83,r2=0.78;P均<0.05)。结论:银杏叶提取物可以通过抑制肾组织中NFκB的活化、减轻过度的炎症反应而延缓糖尿病肾病的发生、发展。

Objective： To examine the effects of Ginkgo biloba extract （GBE） on nuclear factor - κB （NF- κB）, tumor necrosis factor-α （TNF- a） and interleukin- 6 （IL- 6） in rats with diabetic nephropathy （DN）, and investigate its protective effects as well as its mechanisms on DN. Methods： Twenty-two Wistar rats were randomly divided into normal control （group A）, DN group （group B） and DN treated with GBE group （group C）. Diabetes was induced by intraperitoneal injection of streptozotocin （60 mg/kg）. The kidneys were harvested for pathology observation after 12 weeks. The NF - kB activity in renal tissue was measured by electrophoretic mobility shift assays and the levels of TNF - α and IL - 6 were measured by radioimmunoassay in serum. Results： Two rats in group B and C respectively died in the cultivating process. The blood sugar of the survival rats was more than 13.9 mmol/L. The glomerular basement membrane thickening, the numbers of total glomerular cells and monocytes in a glomerulus in group C were more than those of group A and less than those of group B, and those of group B were more than those of group A （all P〈0. 05）. Compared with group A, the NF -κB activity and the levels of TNF - α and IL - 6 were significantly higher in group B and C （all P〈0. 05）. Moreover, they were lower in group C than those in group B （all P〈0.05）. The levels of TNF -α and IL - 6 were positively correlated with the NF -κB activity （r1=0. 83, r2=0. 78; both P〈0.05）. Conclusion： GBE can prevent and cure DN by inhibiting NF - κB activity and depressing inflammatory response.