番茄红素对糖尿病肾病模型大鼠肾纤维化的影响

Effect of Lycopene on Renal Fibrosis in Diabetic Nephropathy Rats

目的:探讨番茄红素(lycopene, Lyc)对糖尿病肾病(diabetic kidney disease, DKD)模型大鼠肾纤维化的影响。方法:采用高糖高脂饲料喂养加腹腔注射链脲佐菌素的方法制备DKD大鼠模型,将模型成功的大鼠随机分为模型组、(低、中、高剂量)Lyc组(10 mg·kg^(-1)、20 mg·kg^(-1)、40 mg·kg^(-1))和二甲双胍组(metformin, Met, 500 mg·kg^(-1)),另设正常对照组,连续给予相应药物8周。称量大鼠体质量并测量空腹血糖水平,测定24 h尿蛋白量(urine protein, UPro)和血尿素氮(blood urea nitrogen, BUN)、肌酐(creatinine, SCr)含量;HE染色观察肾脏病理损伤变化;Masson染色观察肾脏纤维化程度并检测胶原容积分数(collagen volume fraction, CVF);Western Blot法测定肾脏胶原蛋白Ⅰ(Collagen Ⅰ)、Collagen Ⅲ、转化生长因子β(transforming growth factor-β,TGF-β)、Smad2、p-Smad2蛋白表达。结果:与模型组比较,中、高剂量Lyc组和Met组大鼠体质量显著升高(P<0.05;P<0.01),显著降低空腹血糖水平(P<0.01),显著降低UPro和BUN、SCr含量(P<0.01);肾脏病理性形态结构改变和纤维化明显改善,CVF降低(P<0.01);肾脏Collagen Ⅰ、Collagen Ⅲ、TGF-β、p-Smad2表达下调(P<0.01),p-Smad/Smad比值降低(P<0.01)。与Met组比较,高剂量Lyc组大鼠体质量显著升高(P<0.05),UPro和血清BUN、SCr含量降低(P<0.05),CVF降低(P<0.01),Collagen Ⅰ、Collagen Ⅲ、TGF-β、p-Smad表达下调(P<0.05或P<0.01),p-Smad/Smad水平极显著降低(P<0.01)。结论:Lyc对DKD大鼠肾纤维化具有抑制作用,可能与抑制TGF-β/Smad信号通路有关。

Objective: To investigate the effects of lycopene(Lyc) on renal fibrosis in diabetic kidney disease(DKD) rats.Methods: DKD rat model was prepared by feeding high sugar and high fat diet and intraperitoneal injection of streptozotocin.The rats with successful model were randomly divided into model group,(low, medium and high dose) LYC group(10 mg·kg^(-1),20 mg·kg^(-1)and 40 mg·kg^(-1)) and metformin group(500 mg·kg^(-1)).Another normal control group was given corresponding drugs for 8 weeks.The body mass of rats was weighed and the fasting blood glucose level was measured.The 24-hour urinary protein(Upro) and the contents of blood urea nitrogen(BUN) and creatinine(SCr) were measured;the pathological changes of kidney were observed by HE staining.Masson staining was used to observe the degree of renal fibrosis and detect collagen volume fraction(CVF);Collagen Ⅰ and Collagen Ⅲ in kidney, transforming growth factor-β(TGF-β),Smad2 and p-Smad2 protein expression were measured by blot Western Blot.Results: Compared with the model group, the body mass of rats in medium and high dose LYC group and met group increased significantly(P<0.05;P<0.01),the fasting blood glucose level decreased significantly(P<0.01),and the contents of Upro, BUN,SCr decreased significantly(P<0.01);the pathological morphological changes and fibrosis of kidney were significantly improved, and CVF decreased(P<0.01);the expression of kidney collagen Ⅰ,collagen Ⅲ,TGF-β,p-Smad2 decreased(P<0.01),and the ratio of p-Smad/Smad decreased(P<0.01).Compared with Met group, the body mass of rats in high-dose LYC group increased significantly(P<0.05),the contents of Upro and serum BUN and SCr decreased(P<0.05),CVF decreased(P<0.01).The expression of collagen Ⅰ,collagen Ⅲ,TGF-β,p-Smad was down regulated(P<0.05 or P<0.01),and the level of p-Smad/Smad decreased significantly(P<0.01).Conclusion: LYC can inhibit renal fibrosis in DKD rats, which may be related to the inhibition of TGF-β/Smad signaling pathway.