基于TGF-β_(1)/Smads信号通路探讨大蒜素对2型糖尿病大鼠肾纤维化的影响  

Effect of Allicin on Renal Fibrosis in Type 2 Diabetic Rats Based on TGF-β_(1)/Smads Signaling Pathway

作　　者：白敏[1] 李晓翠[1] 靳世英 李慧[1] 吴洁[1] BAI Min;LI Xiaocui;JIN Shiying;LI Hui;WU Jie(Department of Pharmacy,Handan Central Hospital,Handan 056001,China)

机构地区：[1]邯郸市中心医院药学部,河北邯郸056001

出　　处：《西部中医药》2024年第3期5-9,共5页Western Journal of Traditional Chinese Medicine

基　　金：邯郸市科学技术研究与发展计划项目(1823208044ZC)。

摘　　要：目的:探讨大蒜素对2型糖尿病(type 2 diabetes mellitus,T2DM)大鼠肾纤维化和TGF-β_(1)/Smads信号通路的影响以及大蒜素对T2DM所致肾纤维化的作用机制。方法:将50只SD大鼠随机分为正常对照组、模型组和大蒜素低剂量组(5 mg/kg)、大蒜素中剂量组(10 mg/kg)、大蒜素高剂量组(20 mg/kg),每组10只。正常对照组大鼠常规饲养,其余各组采用高糖高脂饲料喂养加腹腔注射链尿佐菌素的方法复制T2DM大鼠模型。造模完成后,大蒜素各剂量组大鼠腹腔注射相应剂量大蒜素溶液,正常对照组及模型组腹腔注射等剂量生理盐水,每天1次,共4周。干预4周后,测定各组大鼠空腹血糖水平,称量体质量;生化分析法测定24h尿蛋白(24 hour urine protein,24h UP)、血清尿素氮(blood urea nitrogen,BUN)、血清肌酐(serum creatinine,SCr)表达水平;苏木精-伊红染色法(hematoxylin-eosin staining,HE)进行肾组织病理学检查;Masson染色进行肾组织纤维化检查并计算胶原容积分数(collagen volume fraction,CVF);免疫组织化学(immunohistochemistry,IHC)法检测肾组织中转化生长因子β_(1)(transforming growth factor-β_(1),TGF-β_(1))、磷酸化Smad2(phospho-Smad2,p-Smad2)、p-Smad3蛋白表达以及Ⅰ型胶原蛋白(collagenⅠ,ColⅠ)和Ⅲ型胶原蛋白(collagenⅢ,ColⅢ)表达。结果:与正常对照组比较,模型组大鼠肾小球增大、系膜基质增厚、肾小管上皮细胞空泡变性、炎性细胞浸润,大鼠空腹血糖、24h UP、BUN、SCr、CVF、TGF-β_(1)、p-Smad2、p-Smad3、Col I、ColⅢ均升高,体质量下降;与模型组比较,大蒜素中、高剂量组大鼠空腹血糖水平降低、体质量升高(P<0.05),24h UP和血清BUN、SCr水平降低(P<0.01),病理学改变改善;与模型组比较,大蒜素低、中、高剂量组大鼠肾组织纤维化改善,肾组织CVF降低(P<0.01);与模型组比较,大蒜素中、高剂量组大鼠肾组织TGF-β_(1)、p-Smad2、p-Smad3、Col I、ColⅢ蛋白表达下调(P<0.01)。Objective:To investigate the effects of allicin on renal fibrosis and transforming growth factor-β_(1)(TGF-β_(1))/Smads signaling pathway in rats with type 2 diabetes mellitus(T2DM),and to explore the mechanism of allicin on renal fibrosis induced by T2DM.Methods:All 50 SD rats were randomized into normal control group,the model group,low(5 mg/kg),moderate(10 mg/kg)and high(20 mg/kg)doses groups of allicin with ten rats in each group.Normal control group accepted normal feeding,the remaining groups were established into T2DM rat models by adopting high glucose and high fat diet plus intraperitoneal injection of streptozotocin(STZ).After successfully modeling,different groups accepted intraperitoneal injection of the medicine,once each day,for four weeks.After four weeks of intervention,to detect the levels of fasting blood glucose(FBG)of the rats in different groups,and to weigh the body mass;biochemical analysis was used to detect the levels of 24h UP,BUN and SCr;HE staining was carried out to perform histopathological examination of the kidney;Masson staining was used for the examination of renal fibrosis and calculate CVF;immunohistochemistry(IHC)was utilized to measure the protein expressions of TGF-β_(1),p-Smad2,p-Smad3,CO1Ⅰand ColⅢin renal tissue.Results:Compared with normal control group,the pathological changes including glomerular enlargement,mesangial matrix thickening,vacuolar degeneration of renal tubular epithelial cells and inflammatory cells infiltration had been significantly improved in the model group,the levels of FBG,24h UP,BUN,SCr,CVF,TGF-β_(1),p-Smad2,p-Smad3,CO1Ⅰand ColⅢraised while the body mass reduced;compared with the model group,the levels of FBG lowered while the body mass increased in the moderate and high doses groups of allicin(P<0.05);the levels of 24hUP and serum BUN,SCr lowered(P<0.01),the pathological changes improved;compared with the model group,the renal fibrosis of the rats in low,moderate and high doses groups of allicin has been improved,CVF in renal tissue wa

关 键 词：2型糖尿病 肾纤维化 胶原蛋白 TGF-β_(1)/Smads信号通路 大蒜素 

分 类 号：R285.5[医药卫生—中药学]