α-硫辛酸对糖尿病肾病大鼠肾纤维化的影响研究

Study on the Influence of α-lipoic Acid on the Renal Fibrosis of Diabetic Nephropathy Rats

目的通过α-硫辛酸对糖尿病肾病模型大鼠肾组织转化生长因子(TGF-β1)、结缔组织生长因子(CTGF)表达的影响,研究其延缓肾脏纤维化的作用及机制,为临床防治糖尿病肾病提供实验依据。方法将健康SD大鼠50只,体重250～300 g,随机分为6组:①正常对照组;②糖尿病对照组;③α-硫辛酸15、30、60mg/(kg.d)。50只采用STZ 45 mg/kg造成糖尿病模型,10只用等量柠檬酸缓冲液腹腔注射,造成模型组,用α-硫辛酸给糖尿病模型组给予剂量。检测各组的大鼠血糖,血清肌酐,肾重指数,制备肾脏石蜡切片,测定肾小球体积(MGA)和计算肾小球平均体积(MGV)。比较MGA和MGV;用SureStep Plus型血糖仪于实验结束前检测空腹血糖;用Western-Blot法检测肾组织TGF-β1、CTGF的表达。结果 DM组大鼠血糖明显升高,血清肌酐无明显变化;与DM组相比,治疗组大鼠血糖,血清肌酐均无统计学意义;DM组大鼠肾重指数明显增加,光镜先显示:DM组的大鼠肾小球体积明显增大,肾小球HE染色区扩大,系膜区增宽,毛细血管管腔受压,肾小球基底膜增厚,α-硫辛酸治疗后上述异常均有不同程度的改善,但未恢复到正常状态图像显示;DM组肾小球平均面积(MGA)和肾小球平均体积(MGV)明显扩大,与其相比,治疗组有不同程度的缩小。结论α-硫辛酸通过抑制肾组织TGF-β1、CTGF的表达而发挥其抗纤维化的作用,从而延缓STZ糖尿病大鼠肾脏纤维化的发展。

Objective Through the influence of α-lipoic acid on the expression of diabetic nephropathy model rats＇ renal organization transformation growth factors,connective tissue growth factor（CTGF）,this paper studies the delay of the function and mechanism of renal fibrosis and provides evidence for the prevention of clinical diabetes and nephropathy.Methods By dividing 50 healthy SD rats weighing 250～300 g into six groups randomly： ① control group,② diabetes control group,③ α-lipoic acid 15,30,60 mg/（kg·d）.50 rats adopting STZ 45 mg/kg only resulted in diabetes model;10 rats with intraperitoneal injection of equal citric acid buffer formed the model group,the diabetes model group were given α-lipoic acid.The rats＇ blood glucose,serum creatinine and renal heavy index were detected,kidney paraffin prepared to determine the glomerular volume（MGA）and calculate the glomerular average volume（MGV）.Comparison was made between MGV and MGA,before the end of the experiment,the fasting blood glucose with Sure Step Plus glucometer got detected,as well as the expressions of kidney tissues TGF β1 and CTGF with the Western-Blot method.Results DM rats＇ blood glucose significantly increased,while the serum creatinine remained unchanged.Compared with the DM group,there showed no statistic significance to the blood glucose and serum creatinine of the treatment group;DM rats＇ renal heavy index increased significantly.DM rats＇ glomerular volume increased,HE glomerular staining area expanded,the mesangium area broadened,and capillary lumen were under pressure,glomerular basement membrane thickened.There were also some improvements after the treatment of α-lipoic acid,though it could not return to the normal image display,DM group glomerular volume（MGA）and glomerular average volume（MGV）significantly increased and,by contrast,the treatment group decreased in some degree.Conclusion By inhibiting the kidney tissues TGF-β1 and CTGF＇s expressions,α-lipoic acid play the role of the antioxidant fibrosis to delay the development of STZ diabetic rats renal fibrosis.