目的:研究蛹虫草(Cordyceps militaris)对糖尿病大鼠肾脏病程发展的抑制作用。方法:采用一次性腹腔注射链脲佐菌素(STZ)的方法建立糖尿病大鼠模型。经蛹虫草(400mg/kg,以体质量计)灌胃8周后,分别检测大鼠空腹血糖值和肾脏指数;并收集大鼠24h尿液,检测尿液中微量白蛋白(mAlb)、β-N乙酰葡萄糖苷酶(NAG)含量;测定血清中尿素氮(BUN)、肌酐(Cr)、尿酸(UA)含量;通过RT-PCR法测定肾脏中转化生长因子β1(TGF-β1)及其Ⅱ型受体(TβRⅡ)、结缔组织生长因子(CTGF)mRNA表达;Western blotting检测肾脏中TGF-β1蛋白表达;免疫组化法检测肾脏中Ⅳ型胶原表达。结果:蛹虫草能显著降低糖尿病大鼠空腹血糖(P〈0.05)、肾脏指数(P〈0.01)、24h排尿量(P〈0.01)、尿微量白蛋白排泄率(UAER)(P〈0.01)和NAG排泄率(P〈0.01);同时能够降低血清中BUN、Cr、UA含量(P〈0.05);下调TGF-β1、TGFβRⅡ和CTGF的mRNA表达(P〈0.01),减少TGF-β1及Ⅳ型胶原的蛋白表达(P〈0.01)。结论:蛹虫草具有良好的降血糖及改善肾脏滤过功能的作用,其机制可能与抑制TGF-β1、TGFβRⅡ和CTGF等基因表达,减少胶原物质在肾脏中的积累有关。
Objective: To explore the inhibitory function of Cordyceps militaris on the development of nephropathy in diabetic rats.Methods: Diabetic rat model was established by intraperitoneally injecting streptozotocin at the dose of 60 mg/kg.After the diabetic rats were administered with Cordyceps militaris at the dose of 400 mg/kg for 8 consecutive weeks,fasting blood glucose level,kidney index,the contents of microalbumin(mAlb) and β-N acetyl glucosaminidase(NAG) in urine,and the contents of blood urea nitrogen(BUN),creatinine(Cr) and uric acid(UA) in serum were determined.The mRNA expression of transforming growth factor-β1(TGF-β1),transforming growth factor beta-receptor II(TGFβR II) and connective tissue growth factor(CTGF) in the kidney were evaluated by semi-quantitative RT-PCR.The expression of collagen IV and TGF-β1 protein in the kidney was determined by immunohistochemistry and Western blot analysis.Results: C.militaris could significantly reduce fasting blood glucose(P0.05),kidney index(P0.01),24-h urine collection(P0.01),the excretion of mAlb(P0.01) and NAG(P0.01) in urine,and serum BUN,Cr and UA levels(P0.05) of diabetic rats.C.militaris administration resulted in a remarkably down-regulation of TGF-β1,TGFβR II and CTGF mRNA expression in the kidney of diabetic rats(P0.01).Western blot and immunohistochemistry analyses revealed a reduction in the expression of TGF-β1 and collagen IV protein due to C.militaris administration.Conclusion: C.militaris has anti-hyperglycemic function and can improve kidney filtration function.The mechanisms of these functions may be due to the inhibited expression of TGF-β1,TGFβR II and CTGF as well as the reduced accumulation of collagen in the mouse kidney.