摘要
目的探讨硫酸吲哚酚(IS)对5/6肾切除慢性肾脏病(CKD)大鼠模型心肌肥大及纤维化的作用。方法20只SD大鼠按随机数字表法分为正常组和5/6肾切除CKD大鼠组(模型组),每组10只。模型组建立5/6肾切除CKD模型。比较2组大鼠体质量、心脏及左心室质量;观察造模前后2组血液中血肌酐、尿素及IS水平;分析2组大鼠心脏组织中有机阴离子转运蛋白-3(OAT-3)、氧化应激烟酰胺腺嘌呤二核苷酸磷酸氧化酶-4(Nox-4)、抗氧化蛋白[核因子-E2相关因子-2(Nrf-2)、下游基因血红素加氧酶-1(HO-1)]、心肌肥大指标[心房利钠肽(ANP)、脑钠肽(BNP)、β-肌球蛋白重链(β-MHC)]及纤维化指标[转化生长因子-β1(TGF-β1)、Smad-3、Ⅰ型胶原蛋白(CollagenⅠ)mRNA]表达水平。结果与正常组比较,模型组体质量降低,心脏和左心室质量显著增加(P<0.05,P<0.01)。模型组大鼠造模12周后血肌酐、尿素及IS水平高于造模前和正常组(P<0.05,P<0.01)。与正常组比较,模型组大鼠心脏组织中OAT-3、Nox-4、ANP、BNP、β-MHC、TGF-β1、Smad-3及CollagenⅠmRNA表达水平升高,Nrf-2、HO-1 mRNA表达水平降低(P<0.01)。结论在5/6肾切除CKD大鼠中IS经OAT-3摄取,进而激活氧化应激反应,最终引起心肌肥大及纤维化。
Objective To investigate the effect of indoxyl sulfate(IS)on myocardial hypertrophy and fibrosis in chronic kidney disease(CKD)rats undergoing 5/6 nephrectomy.Methods Twenty SD rats were divided into normal group and 5/6 nephrectomized CKD rats(model group)according to random number table method,with 10 rats in each group.In the model group,5/6 nephrectomized CKD rat model was established.The body mass,heart and left ventricular mass of the two groups were compared.The levels of serum creatinine(SCr),urea and IS in the two groups were observed before and after modeling.The organic anion transporter-3(OAT-3),oxidative stress of nicotinamide adenine dinucleotide phosphate(NADPH)oxidase-4(Nox-4),antioxidant protein[nuclear factor-E2-associated factor-2(Nrf-2),downstream gene heme oxygenase-1(HO-1)]and mRNA expression levels of myocardial hypertrophy indexes[atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),β-myosin heavy chain(β-MHC)]and fibrosis indicators[transforming growth factor-β1(TGF-β1),Samad-3,CollagenⅠ]in the heart tissues of rats in the two groups were analyzed.Results Compared with the normal group,the body mass was decreased,and the heart and left ventricular mass was increased significantly in the model group(P<0.05,P<0.01).SCr,urea and IS levels in the model group at 12 weeks after modeling were significantly higher than those before modeling,and higher than those in normal group(P<0.05,P<0.01).Compared with normal group,mRNA expression levels of OAT-3,Nox-4,ANP,BNP,β-MHC,TGF-β1,Samad-3 and CollagenⅠin heart tissues of model group were increased(P<0.01),while mRNA expression levels of Nrf-2 and HO-1 were significantly decreased(P<0.01).Conclusion Uptake of IS by OAT-3 in 5/6 nephrectomized CKD rats activated oxidative stress response and eventually caused cardiac hypertrophy and fibrosis.
作者
买买提艾力·艾则孜
买买提·依斯热依力
王琴
邵劲杰
杜宇奎
王永康
刘筠
张总刚
MAIMAITIAILI Aizezi;MAIMAITI Yisireyili;WANG Qin;SHAO Jinjie;DU Yukui;WANG Yongkang;LIU Jun;ZHANG Zonggang(The First Department of Cardiac Surgery,Cardiovascular and Panvascular Medical Diagnosis and Treatment Center,the People's Hospital of Xinjiang Uygur Autonomous Region,Urumqi 830001,China;Medical Research and Transformation Center,Cardiovascular and Panvascular Medical Diagnosis and Treatment Center,the People's Hospital of Xinjiang Uygur Autonomous Region,Urumqi 830001,China)
出处
《转化医学杂志》
2023年第4期133-137,142,共6页
Translational Medicine Journal
基金
新疆维吾尔自治区自然科学基金(2021D01C175,2020D01C090)。
