摘要
目的探讨外源性硫化氢(H_(2)S)对尿毒症心肌病(UCM)大鼠心肌早衰和心肌纤维化的影响。方法雄性SD大鼠48只按随机数字表法分成假手术组(Sham组)、模型组(UCM组)、H_(2)S治疗组(UCM+H_(2)S组)以及H_(2)S对照组(H_(2)S组)。其中UCM组、UCM+H_(2)S组用经典5/6肾切除法造模,而Sham组及H_(2)S组仅游离双肾。建模后UCM+H_(2)S组和H_(2)S组大鼠每日注射硫氢化钠(NaHS,50μmol/kg),Sham组和UCM组注射同剂量生理盐水。干预8周,心脏超声检测大鼠左心室的短轴缩短率(LVFS);Masson染色法评估心肌纤维化情况,计算胶原容积分数(CVF);免疫组化染色检测心肌Ⅲ型胶原表达;β-半乳糖苷酶染色检测衰老心肌细胞;蛋白免疫印迹法检测心肌中沉默信息调节因子-1(SIRT1)、NOD样受体家族3(NLRP3)、白细胞介素(IL)-1β、P21、P19、P53蛋白表达。结果与Sham组比较,UCM组LVFS明显下降,心肌CVF、Ⅲ型胶原的阳性表达率、β-半乳糖苷酶染色阳性率升高,NLRP3、IL-1β、P19、P21及P53表达增多,SIRT1蛋白表达减少(P<0.05);而UCM+H_(2)S组较UCM组大鼠心肌CVF、Ⅲ型胶原、β-半乳糖苷酶染色阳性率降低,NLRP3、IL-1β、P19、P21及P53蛋白表达量减少,SIRT1蛋白表达增多(P<0.05)。结论外源性H_(2)S能改善尿毒症大鼠心肌纤维化,机制可能与其上调SIRT1抑制心肌早衰有关。
Objective To investigate the effect of hydrogen sulfide(H_(2)S) on premature myocardial aging and myocardial fibrosis in uremic rats.Methods Forty-eight male SD rats were randomly divided into the sham operation group(Sham group),the model group(uremic cardiomyopathy,UCM group),the H_(2)S treatment group(UCM+H_(2)S group) and the H_(2)S group.Rats in the UCM group and the UCM+H_(2)S group were modeled by the classic 5/6 nephrectomy method.After the model was established,rats in the UCM+H_(2)S group and the H_(2)S group were injected with sodium hydrosulfide(NaHS,50 μmol/kg) every day for 8 weeks,while the Sham group and the UCM group were injected with the same amount of normal saline.Left ventricular shortening rate(LVFS) was measured by cardiac ultrasound.Masson staining was used to evaluate myocardial fibrosis,and collagen volume fraction(CVF) was calculated.The expression of type Ⅲ collagen in myocardium was detected by immunohistochemistry.β-galactosidase staining was used to detect senescent myocardial cells.The expression levels of SIRT1,NLRP3,interleukin(IL)-1β,P21,P19 and P53 proteins in myocardium were measured by Western blot assay.Results Compared with the Sham group,LVFS was significantly decreased in the UCM group,the relative expression levels of CVF,type Ⅲ collagen and the positive rate of(3-galactosidase staining were increased,the expressions of NLRP3,IL-1β,P19,P21 and P53 were increased,and the expression of SIRT1 protein was decreased(P <0.05).Compared with the UCM group,the relative expression levels of CVF,type Ⅲ collagen and positive staining rate of(3-galactosidase were decreased in the UCM+H_(2)S group,and the protein expressions of NLRP3,IL-1β,P19,P21 and P53 were decreased,while the protein expression of SIRT1 was increased(P <0.05).Conclusion Exogenous H_(2)S can improve myocardial fibrosis in uremic rats,and the mechanism may be related to the upregulation of SIRT1 and the inhibition of premature myocardial senescence.
作者
刘达
肖婷
梁彪
宋熊
王森
赵俊雄
杨军
LIU Da;XIAO Ting;LIANG Biao;SONG Xiong;WANG Sen;ZHAO Junxiong;YANG Jun(Department of Cardiology,the First Affiliated Hospital of University of South China,Hengyang 421000,China;Department of Cardiology,Longhua District Central Hospital;Department of Cardiology,People's Hospital of Ningxiang)
出处
《天津医药》
CAS
北大核心
2022年第12期1276-1281,共6页
Tianjin Medical Journal
基金
国家自然科学基金面上项目(81870230)
湖南省卫生健康委员会科技计划重点项目(20201913)
湖南省自然科学基金科卫联合基金项目(2019JJ80033)
深圳市龙华区医疗卫生机构区级科研项目(2020035)。
