日本血吸虫重组半胱氨酸蛋白酶抑制剂对小鼠心肌梗死预后的影响及其免疫调节机制  

Effect of recombinant cysteine protease inhibitor of Schistosoma japonicum on prognosis of myocardial infarction in mice and its immuno-regulation mechanism

作　　者：李燕楠 杨小迪[2] 陈思宇 颉丽英 刘思麒 高尔和 左琳[1] LI Yan-nan;YANGXiao-di;CHEN Si-yu;XIE Li-ying;LIU Si-qi;GAO Er-he;ZUO Lin(Key Laboratory of Cellular Physiology of the Ministry of Education,Department of Physiology,College of Basic Medicine,Shanxi Medical University,Taiyuan 030001,Shanxi Province,China)

机构地区：[1]山西医科大学细胞生理学教育部重点实验室基础医学院生理学系,山西太原030001 [2]蚌埠医学院安徽省感染与免疫重点实验室微生物学与寄生虫学系,安徽蚌埠233030 [3]天普大学医学院转化医学中心,美国费城19140

出　　处：《中国生物制品学杂志》2022年第1期55-62,共8页Chinese Journal of Biologicals

基　　金：山西省“1331工程”重点学科建设计划(XK201708)。

摘　　要：目的探讨日本血吸虫重组半胱氨酸蛋白酶抑制剂(r Sjcystatin)对小鼠心肌梗死(myocardial infarction,MI)预后的影响及其免疫调节机制。方法建立小鼠MI模型,分别于术后1、3、5、7、14、28 d经腹腔注射PBS及10、25μg r Sjcystatin。术后28 d,记录MI小鼠的生存率及心脏黏连率;通过超声心动图观察心功能变化;Masson三色染色法检测心脏结构重构情况。术后7 d,HE染色法检测小鼠心脏损伤情况;CD45免疫组化染色法检测炎症细胞浸润程度;ELISA法检测小鼠血清中主要炎症因子肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-10(interleukin-10,IL-10)、IL-6、转化生长因子-β1(transforming growth factor-β1,TGF-β1)的分泌水平。结果MI术后28 d,与PBS组比较,两剂量r Sjcystatin治疗组小鼠存活率呈上升趋势,心脏黏连率降低;25μg r Sjcystatin治疗组小鼠左室射血分数(left ventricular ejection fraction,LVEF)和左室短轴缩短率(left ventricular fraction shortening,LVFS)明显升高(P<0.05),左室的梗死面积百分比明显减少(P<0.01);两剂量r Sjcystatin治疗组小鼠左室舒张末内径(left ventricular diastolic internal diameter,LVID,d)显著减小(P<0.05),左室壁厚度明显增加(P<0.001);与10μg r Sjcystatin治疗组比较,25μg r Sjcystatin治疗组的LVEF和LVFS均明显升高(P<0.05),LVID,d差异无统计学意义(P﹥0.05),左室梗死面积百分比显著减小(P<0.05),室壁厚度明显增加(P<0.001)。MI术后7 d,与PBS组比较,两剂量r Sjcystatin治疗组炎性细胞的浸润减少,心肌纤维的破坏减轻;25μg r Sjcystatin治疗组棕黄色炎性细胞颗粒的平均光密度值显著低于PBS组及10μg r Sjcystatin治疗组(P分别为<0.05和<0.001);与PBS组比较,25μg r Sjcystatin组小鼠血清TNF-α和IL-6的含量显著降低(P分别为<0.05及<0.01),TGF-β1含量显著升高(P<0.001),IL-10含量呈升高趋势,但差异无统计学意义(P>0.05)。结论r Sjcystatin可通过适度减弱炎细胞浸润、降�Objective To investigate the effect of recombinant cysteine protease inhibitors(r Sjcysatin)of Schistosoma japonicum on myocardial infarction(MI)in mice as well as the relevant immune-regulation mechanism.Methods The mouse model of MI was established.The model mice were injected i.p.with PBS and r Sjcystatin at dosages of 10 and 25μg respectively 1,3,5,7,14 and 28 d after operation.The survival rate and heart adhesion rate of mice with MI were recorded 28 d after operation,while the change of cardiac function was observed by echocardiography and the cardiac structural remodeling by Masson trichrome staining.The cardiac lesion of mice was observed by HE staining 7 d after operation,while the infiltration of inflammatory cells by CD45 immunohistochemical staining,and the secretion levels of tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),IL-6 and transforming growth factor-β1(TGF-β1)in sera were determined by ELISA.Results Twenty-eight days after MI,as compared with those in PBS group,the survival rate of mice treated with r Sjcystatin at two dosages increased,while the heart adhesion rate decreased;the left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)of mice treated with 25μg r Sjcystatin increased significantly(P<0.05),while the left ventricular infarct size decreased significantly(P<0.01);the left ventricular diastolic internal diameter(LVID,d)of mice treated with 10 and 25μg r Sjcystatin decreased significantly(P<0.05),while the thickness of left ventricular wall increased significantly(P<0.001).However,compared with those treated with 10μg r Sjcystatin,the LVEF and LVFS of mice treated with 25μg r Sjcystatin increased significantly(P<0.05),while LVID(d)showed no significant difference(P>0.05),the percentage of left ventricular infarct area decreased significantly(P<0.05),and the thickness of left ventricular wall increased significantly(P<0.001).Seven days after MI,compared with those in PBS group,the infiltration of inflammatory cells and the destruction of m

关 键 词：日本血吸虫 半胱氨酸蛋白酶抑制剂 心肌梗死 炎症 

分 类 号：R331[医药卫生—人体生理学]