3-甲基腺嘌呤对风湿性心脏病瓣膜纤维化的影响  

Effect of 3-methyladenine on valve fibrosis in rheumatic heart disease

作　　者：朱晓莉 谢晓勇[1] 黄柳柳[1] 罗程[1] 黎玉贵 温大帅 贺洲 ZHU Xiaoli;XIE Xiaoyong;HUANG Liuliu;LUO Cheng;LI Yugui;WEN Dashuai;HE Zhou(Department of Cardiothoracic Surgery,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,Guangxi,China)

机构地区：[1]广西医科大学第一附属医院心胸外科,广西南宁市530021

出　　处：《微创医学》2023年第4期435-439,共5页Journal of Minimally Invasive Medicine

基　　金：广西自然科学基金(编号:2019GXNSFAA185055)。

摘　　要：目的 探讨3-甲基腺嘌呤(3-MA)对风湿性心脏病(RHD)瓣膜纤维化相关指标的影响。方法 取30只Lewis雌性大鼠,利用电脑随机数将大鼠分为正常组、模型组和实验组,每组10只。模型组和实验组通过后足垫、腹部皮下注射抗原Ⅰ、抗原Ⅱ造模,大鼠多处关节出现红肿,B超检查显示二尖瓣有不同程度反流,表明RHD模型建立成功。建模成功后,第8~9周,实验组大鼠于腹部皮下注射3-MA 2.5 mg/kg, 1次/周,模型组大鼠腹部皮下注射等量生理盐水;第10~24周,模型组、实验组大鼠腹部皮下注射0.5 mL抗原Ⅱ,1次/周,正常组大鼠在相同时间以同样方式注射等量生理盐水。采用免疫印迹(Western blot)法检测3组大鼠二尖瓣组织中PI3K、Akt、α-平滑肌肌动蛋白(α-SMA)、LC3Ⅱ及Ⅰ型胶原蛋白的相对表达量;采用ELISA法检测肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、白介素-8(IL-8)水平。结果 正常组、实验组、模型组大鼠的二尖瓣组织中PI3K、Akt、LC3Ⅱ的相对表达量依次升高,组间差异均有统计学意义(均P<0.05);模型组α-SMA、Ⅰ型胶原蛋白的相对表达量均高于正常组、实验组,差异均有统计学意义(均P<0.05);正常组与实验组的α-SMA、Ⅰ型胶原蛋白相对表达量比较,差异均无统计学意义(均P>0.05)。正常组、实验组、模型组大鼠的二尖瓣组织中TNF-α、IL-6、IL-8水平依次升高,组间差异均有统计学意义(均P<0.05)。结论 3-MA能够有效抑制RHD大鼠二尖瓣组织自噬,减轻心脏瓣膜纤维化;调控PI3K/Akt信号通路可能是3-MA起抑制纤维化的作用机制之一;自噬作用的调控可能与TNF-α、IL-6及IL-8水平具有一定的相关性。Objective To investigate the effect of 3-methyladenine(3-MA)on related indexes of valve fibrosis in rheumatic heart disease(RHD).Methods Thirty female Lewis rats were divided into normal group,model group and experimental group by computer random number method,with 10 rats in each group.The model group and experimental group were modeled by subcutaneous injection of antigenⅠand antigenⅡinto the hind foot pad and abdomen.Multiple joints of the rats showed redness and swelling,and two-dimensional ultrasonography showed different degrees of mitral valve regurgitation,indicating that the model was successfully established.After successful modeling,rats in the experimental group were injected subcutaneously with 3-MA 2.5 mg/kg once a week in the abdomen at the 8th to 9th week,while rats in the model group were injected subcutaneously with the same amount of normal saline in the abdomen.From 10th to 24th week,rats in the model group and experimental group were injected with 0.5 mL antigenⅡsubcutaneously in the abdomen once a week,while rats in the normal group were injected with the same amount of normal saline at the same time and in the same way.The relative expressions of PI3K,Akt,alpha-smooth muscle actin(α-SMA,)LC3Ⅱand typeⅠcollagen in the mitral valve tissues of the three groups were detected by Western blot.The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-8(IL-8)were detected by ELISA.Results The relative expressions of PI3K,Akt and LC3Ⅱin mitral valve tissue of normal group,experimental group and model group increased in turn,and the differences among the groups were statistically significant(all P<0.05).Compared with the normal group and the experimental group,the relative expressions ofα-SMA,typeⅠcollagen were higher in the model group,with statistically significant differences(all P<0.05).There were no statistically significant differences in the relative expressions ofα-SMA and typeⅠcollagen between the normal group and the experimental group(all P>0.05).T

关 键 词：风湿性心脏病 3-甲基腺嘌呤 PI3K/AKT 瓣膜纤维化 

分 类 号：R541.2[医药卫生—心血管疾病]