姜黄素类似物L6H4对2型糖尿病大鼠肾脏的保护作用

Protective effects of Curcumin analogue L6H4 on kidney from type 2 diabetic rats

目的:探讨姜黄素类似物L6H4对2型糖尿病大鼠肾脏的保护作用及机制。方法:24只SPF级雄性SD大鼠,随机分成3组(n=8):对照组(NC组)、糖尿病组(DM组)和糖尿病治疗组(DT组),采用高脂饮食加腹腔注射低剂量链脲佐菌素诱导2型糖尿病大鼠模型。DT组按0.2 mg/kg·d剂量的L6H4灌胃8周。治疗结束后测24h尿蛋白、空腹血糖(FBG)、甘油三酯(TG)、血肌酐(Scr)、血尿素氮(BUN)、尿酸(UA)。采用光镜和透射电镜观察大鼠肾脏的形态学改变;用免疫组化法测定大鼠肾脏组织转化生长因子-β1(TGF-β1)、纤维粘连蛋白(FN)、四型胶原(Col-IV)的表达水平。结果:DM组大鼠24 h尿蛋白、FBG、TG、Scr、BUN均明显升高(P<0.01),肾小球体积增大、不规则,弥漫性系膜基质增多,伴基底膜不同程度的增生肥厚及足突融合现象;肾组织的TGF-β1、FN、Col-IV表达水平明显增加(P<0.05)。经L6H4治疗后,DT组的24 h尿蛋白、FBG、TG、Scr、BUN水平明显下降(P<0.01),大鼠肾小球形态较规则,系膜区基质明显减少,足细胞肿胀、融合现象减轻;肾组织的TGF-β1、FN、Col-IV表达明显减少(P<0.05)。结论:L6H4可能通过下调TGF-β1的表达,抑制FN、Col-IV的大量分泌,减轻细胞外基质的沉积,从而起到保护2型糖尿病大鼠肾脏的作用。

Objective： To investigate the protective effect of curcumin analogue L6H4 on the kidney from the type 2 diabetic rats.Methods： Twenty-four SPF male SD rats were randomly divided into 3 groups（ n = 8） ： normal control group（ NC）,diabetes mellitus group（ DM） and DM ＋ L6H4-treatment group（ DT）. After rats were fed with high-fat diet for 4 weeks,both the DM and DT groups were injected with streptozotocin intraperitoneally to induce type 2 diabetes mellitus models. The rats in DT group were given L6H4 by gavage at the dose of 0. 2 mg / kg·d for 8 weeks. After the treatment,the 24 h urinary protein,fasting blood glucose（ FBG）,triglyceride（ TG）,serum creatinine（ Scr）,blood urea nitrogen（ BUN） and uric acid（ UA） were detected biochemically. The pathological changes of the kidneys were observed under light and transmission electron microscopes. The expressions of TGF-β1,FN and Col IV were detected by immunohistochemistry. Results： The levels of the 24 h urinary protein,FBG,TG,Scr and BUN were elevated significantly in diabetic group（ P〈0. 01）. The glomerular volume of DM group rats became irregularly enlarged,diffused mesangial matrix accumulated,with basal membrane proliferous hypertrophy and fusion phenomenon of foot process,the expressions of TGF-β1,FN and Col-IV were elevated significantly（ P〈0. 05）. After treated with L6H4,the levels of the 24 h urinary protein,FBG,TG,Scr and BUN were decreased in DT group compared to DM group（ P〈0. 01）,the morphological changes of kidney were ameliorated. The expression levels of TGF-β1,FN and Col-IV were downregulated（ P〈0. 05）. Conclusion： L6H4 exerts the protective effect on kidneys of type 2diabetic rats by reducing expression of TGF-β1,inhibiting secretion of Col-IV and FN,relieving the deposition of the extracellular matrix.