摘要
目的探讨抗氧化剂α-硫辛酸(α-lipoic acid,ALA)对糖尿病肾病(DN)的肾保护作用及其对肾组织转化生长因子-β1(transforming growth factor-β1,TGF-β1)和结缔组织生长因子(connective tissue growth factorCTGF)表达的影响。方法建立STZ诱导的DN大鼠模型,给予ALA(35 mg/kg·d^(-1))腹腔注射预防性治疗,分别于第12周和第20周处死动物。检测血糖、肾功能、24 h尿蛋白定量,PAS染色观察肾组织结构改变,分光光度仪检测肾组织和血清中还原型谷胱甘肽(GSH)、氧化型谷胱甘肽(GSSG)水平,GSH/GSSG比值。免疫组化方法检测肾组织中TGF-β1和CTGF表达。结果与对照组相比,第12周和20周DN大鼠血糖明显升高,24 h尿蛋白定量增高,肾小球滤过率增加。病理组织PAS染色显示肾小球系膜增生、肾小管上皮空泡变性等改变。肾组织匀浆及血清中GSH水平下降,GSSG水平增高,GSH/GSSG比值降低,肾组织中TGF-β1和CTGF表达明显上调。而ALA组24 h尿蛋白定量减少,病理改变减轻,GSH水平上升,GSH/GSSG比值增高,肾组织中TGF-Bl和CTGF表达较DN组明显下调。结论 ALA可通过增强谷胱甘肽活性,减少氧化应激而下调肾组织TGF-Bl和CTGF表达,进而改善DN大鼠肾组织结构和肾功能,在防治DN方面有良好的应用前景。
Objective To investigate the effects of a-lipoic acid（ALA） on expression of transforming growth factor-fJl（TGF-β1） and connective tissue growth factor（CTGF） in the kidney of streptozocin（STZ） -induced diabetic rats.Methods Diabetes was induced by intraperitoneal injection of 60 mg/kg STZ in rats,and the diabetic rats were randomly divided into DN group（n = 9,treated with physiological saline） and ALA group（n = 8,treated with ALA 35 mg/kg by intraperitoneal injection every other day）.The rats of control group（n = 10） were given vehicle citrate buffer in the same dose.Rats were sacrificed at 12 weeks and 20 weeks of study.The three groups were compared in terms of blood glucose,creatinine clearance,urine protein,renal pathological changes.The concentration of reduced glutathione（GSH）,glutathione disulfide（GSSG） and the ratio of GSH/ GSSG were measured by spectrophotometry,and the expression of TGF-βi and CTGF was detected by immunohistochemical staining.Results Compared with control group,the blood glucose level and urine protein in DN rats were significantly increased;the creatinine clearance decreased;and the GSH levels were decreased,the GSSG levels increased,the ratio of GSH/GSSG were increased;the expression of TGF-βl and CTGF in kidney was greatly increased.Compared with DN group,the urine protein level,creatinine clearance and the intensity of GSSG in ALA group were significantly decreased;the levels of GSH and the ratio of GSH/GSSG were increased;the expression of TGF-β1 and CTGF decreased and the morphological changes were ameliorated significantly.Conclusion ALA can suppress oxidative stress,reverse histological changes of glomerulosclerosis and attenuates the overexpression of TGF-β1 and CTGF in diabetic nephropathy in rats.
出处
《同济大学学报（医学版）》
CAS
2011年第6期9-15,共7页
Journal of Tongji University(Medical Science)
基金
上海市卫生局青年科研基金(2009Y081)
