过表达中介素对感染性休克大鼠心肌损伤的保护机制  

Protective mechanism of overexpression of intermedin against myocardial injury in rats with septic shock

作　　者：杨洋[1] 王晓静 王前 赵欢 韩宁娟 YANG Yang;WANG Xiao-jing;WANG Qian;ZHAO Huan;HAN Ning-juan(Jiyuan Vocational and Technical College,Jiyuan,Henan 459000,China;不详)

机构地区：[1]济源职业技术学院医学护理系,河南济源459000 [2]郑州市第七人民医院科教科,河南郑州450000 [3]济源市人民医院儿科,河南济源459000 [4]国健呈诺生物科技(北京)有限公司,河南郑州450000

出　　处：《中华医院感染学杂志》2023年第3期335-339,共5页Chinese Journal of Nosocomiology

基　　金：河南省医学教育指导性基金资助项目(Wjlx2020248)。

摘　　要：目的探究过表达中介素(IMD)对感染性休克大鼠心肌损伤的保护机制。方法将40只大鼠随机分为假手术组(Sham组),盲肠结扎穿孔术(CLP)组,腺相关病毒载体(AAV)+CLP组,AAV-IMD+CLP组,每组10只。分别进行心肌载体病毒转染并验证,转染成功3周后行盲肠结扎穿孔术建立脓毒症大鼠模型,Sham组开腹后不进行盲肠结扎、穿孔操作。手术24 h后,超声心动图检测大鼠心功能,酶联免疫吸附法检测大鼠血清肌钙蛋白I(cTnI)、肌酸激酶(CK)、乳酸脱氢酶(LDH)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、IL-1β水平,检测心肌组织丙二醛(MDA)、超氧化物歧化酶(SOD)水平,Western blot检测心肌组织NOD样受体蛋白3(NLRP3)、凋零相关斑点样蛋白(ASC)和胱天蛋白酶1(Caspase-1)蛋白表达水平。结果心肌转染3周后,Western blot结果显示转染成功(P<0.05);与CLP组比较,AAV-IMD+CLP组心率(HR)、左心室收缩和舒张峰值速率(±LVdp/dtmax)、左心室舒张末压(LVEDP)、左心室收缩末压(LVESP)、平均动脉压(mABP)升高(P<0.05),血清肌钙蛋白I(cTnI)、肌酸激酶(CK)、乳酸脱氢酶(LDH)水平降低(P<0.05),血清肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、IL-1β水平降低(P<0.05),心肌组织丙二醛(MDA)水平降低(P<0.05),超氧化物歧化酶(SOD)水平升高(P<0.05),NLRP3、ASC、Caspase-1蛋白表达均下调(P<0.05)。结论过表达IMD对感染性休克大鼠心肌损伤具有保护作用,可能与抑制NLRP3/ASC/Caspase-1信号通路相关。OBJECTIVE To investigate the protective mechanism of overexpression of intermedin(IMD) on myocardial injury in rats with septic shock.METHODS Totally 40 rats were randomly divided into sham operation group(Sham group),cecal ligation and puncture group(CLP group),adeno-associated virus vector(AAV)+CLP group and AAV-IMD+CLP group,with 10 rats in each group.The myocardial vector virus was transfected and verified respectively.After 3 w of successful transfection,the rat model of sepsis was established by cecal ligation and perforation,and the Sham group did not undergo cecal ligation and perforation after laparotomy.After 24 h of surgery,echocardiography was performed to detect the cardiac function of rats,and enzyme-linked immunosorbent assay was adopted to detect the levels of serum cardiac troponin I(cTnI),creatine kinase(CK),lactate dehydrogenase(LDH),tumor necrosis factor α(TNF-α),interleukin 6(IL-6) and IL-1β.The levels of malondialdehyde(MDA) and superoxide dismutase(SOD) in myocardial tissues were detected,and Western blot was used to detect the protein expression levels of Nod-like and pyrin domain containing receptor 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC) and Caspase-1 in myocardial tissues.RESULTS After 3 w of myocardial transfection,Western blot results showed that the transfection was successful(P<0.05).Compared with CLP group,the heart rate(HR),left ventricular peak systolic and diastolic velocity(±LVdp/dtmax),left ventricular end diastolic pressure(LVEDP),left ventricular end systolic pressure(LVESP) and mean arterial pressure(mABP) were increased(P<0.05),the levels of serum cTnI,CK and LDH were decreased(P<0.05),and the levels of serum TNF-α,IL-6 and IL-1β were reduced(P<0.05),the MDA level in myocardial tissue was lowered(P<0.05) while the SOD level was risen(P<0.05),and the protein expressions of NLRP3,ASC and Caspase-1 were down-regulated(P<0.05) in AAV-IMD+CLP group.CONCLUSION Overexpression of IMD had a protective effect on myocardial

关 键 词：中介素 感染性休克 大鼠 心肌损伤 NOD样受体蛋白3/凋零相关斑点样蛋白/胱天蛋白酶1信号通路 

分 类 号：R631.4[医药卫生—外科学]