摘要
目的:探讨二氧化硫(SO_(2))对链脲佐菌素(STZ)和高糖高脂饮食诱导的2型糖尿病(T2DM)大鼠心肌纤维化的改善作用及对细胞凋亡和转化生长因子β1(TGF-β1)/Smad同源物2/3(Smad2/3)通路的影响,阐明SO_(2)改善糖尿病心肌纤维化可能的分子机制。方法:40只雄性SD大鼠随机分为对照组、T2DM组、T2DM+SO_(2)组和SO_(2)组。除对照组和SO_(2)组外,T2DM组和T2DM+SO_(2)组大鼠采用腹腔注射STZ(35 mg·kg^(-1))和高糖高脂饮食建立T2DM大鼠模型,T2DM+SO_(2)组和SO_(2)组大鼠腹腔注射外源性SO_(2)供体[亚硫酸钠(Na2SO3)/亚硫酸氢钠(NaHSO3),85 mg·kg^(-1)·d^(-1)],共8周,采用Masson染色观察各组大鼠心肌组织纤维化病理形态表现,并计算各组大鼠心肌胶原容积分数,采用Western blotting法检测各组大鼠心肌组织中相关蛋白表达水平。结果:与对照组比较,T2DM组大鼠心肌组织形态结构紊乱,心肌胶原纤维形成明显增加,心肌胶原容积分数明显升高(P<0.01),心肌组织中α平滑肌肌动蛋白(α-SMA)、Ⅲ型胶原(ColⅢ)、B细胞淋巴瘤2(Bcl-2)相关X蛋白(Bax)、TGF-β1、Smad2和Smad3蛋白表达水平明显升高(P<0.01),Bcl-2蛋白表达水平明显降低(P<0.01);与T2DM组比较,T2DM+SO_(2)组大鼠心肌组织形态结构有所改善,心肌胶原纤维形成明显减少,心肌胶原容积分数明显降低(P<0.01),心肌组织中α-SMA、ColⅢ、Bax、TGF-β1、Smad2和Smad3蛋白表达水平明显降低(P<0.01),Bcl-2蛋白表达水平明显升高(P<0.01)。与对照组比较,SO_(2)组大鼠上述各项指标差异均无统计学意义(P>0.05)。结论:SO_(2)可通过抑制促凋亡相关蛋白和TGF-β1/Smad2/3通路蛋白表达,缓解T2DM大鼠心肌纤维化。
Objective:To investigate the ameliorative effects of sulfur dioxide(SO_(2))on myocardial fibrosis in the type 2 diabetes mellitus(T2DM)rats induced by streptozocin(STZ)and high glucose and high fat diet and the effects on apoptosis and transforming growth factor-β1(TGF-β1)/Smad family member 2/3(Smad2/3)pathway,and to clarify the possible molecular mechanisms of SO_(2) in ameliorating diabetic myocardial fibrosis.Methods:Forty male SD rats were randomly divided into control group,T2DM group,T2DM+SO_(2) group,and SO_(2) group.Except for control group and SO_(2) group,the rats in T2DM and T2DM+SO_(2) groups were used to establish the T2DM rat models by intraperitoneal injection of STZ(35 mg·kg-1)and high glucose and high fat diet,and the rats in T2DM+SO_(2) and SO_(2) groups were injected intraperitoneally with exogenous SO_(2) donors[sodium sulfite(Na_(2)SO_(3))/sodium bisulfite(NaHSO3),85 mg·kg^(-1)·d^(-1)]for 8 weeks;the pathomorphology of myocardial fibrosis of the rats in various groups was observed by Masson staining,and the myocardial collagen volume fractions of the rats in various groups were calculated,and the expression levels of relevant proteins in myocardial tissue of the rats in various groups were detected by Western blotting method.Results:Compared with control group,the myocardial tissue of the rats in T2DM group showed morphology and structural disorders,the myocardial collagen fiber formation was significantly increased,the myocardial collagen volume fraction was significantly increased(P<0.01),the expression levels ofα-smooth muscle actin(α-SMA)and typeⅢcollagen(ColⅢ),B-cell lymphoma-2(Bcl-2)associated X protein(Bax),TGF-β1,Smad2,and Smad3 proteins were significantly increased(P<0.01),and the expression level of Bcl-2 protein was significantly decreased(P<0.01).Compared with T2DM group,the morphological structure of myocardial tissue of the rats in T2DM+SO_(2) group was improved,the myocardial collagen fiber formation and the myocardial collagen volume fraction were significantly de
作者
赵俊雄
吴倩
聂连桂
刘盛权
江振涛
陈坚
肖婷
杨军
ZHAO Junxiong;WU Qian;NIE Liangui;LIU Shengquan;JIANG Zhentao;CHEN Jian;XIAO Ting;YANG Jun(Department of Cardiology,First Affiliated Hospital,Hengyang Medical School,University of South China,Hengyang 421001,China;Department of General Medicine,Second Affiliated Hospital,Hengyang Medical School,University of South China,Hengyang 421001,China;Department of Cardiology,Affiliated Nanhua Hospital,Hengyang Medical School,University of South China,Hengyang 421001,China;Department of Intensive Care Unit,Affiliated Nanhua Hospital,Hengyang Medical School,University of South China,Hengyang 421001,China;Department of Cardiology,Affiliated Longhua Central Hospital,Guangdong Medical University,Shenzhen 518110,China)
出处
《吉林大学学报（医学版）》
CAS
CSCD
北大核心
2023年第1期8-14,共7页
Journal of Jilin University：Medicine Edition
基金
国家自然科学基金项目(81870230)
湖南省卫健委临床重大专项项目(20201913)
湖南省自然科学基金委员会科卫联合项目(2021JJ70035)
湖南省自然科学基金委员会青年基金项目(2021JJ40499)
广东省深圳市龙华区医疗卫生机构区级科研项目(2020035)。
