环磷酸腺苷抑制结缔组织生长因子表达对小鼠心肌梗死后心肌纤维化的影响  

Cyclic adenosine monophosphate regulate myocardial fibrosis after myocardial infraction by inhibiting connective tissue growth factor expression level in mice

作　　者：刘波[1] 黄晓帆[1] 李冬寒[1] 王生伟[1] 杜心灵[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院心血管外科,武汉430022

出　　处：《中华实验外科杂志》2015年第8期1826-1830,共5页Chinese Journal of Experimental Surgery

基　　金：高等学校博士学科点专项科研基金资助项目（20110142110009）

摘　　要：目的观察环磷酸腺苷（cAMP）对小鼠心肌梗死后结缔组织生长因子（CTGF）的调控作用以及对心肌纤维化的影响。方法72只C57BL雄性小鼠，随机分为假手术组（MS组）、心肌梗死组（MI组）及药物干预组（MT组），每组各24只。术后1周MT组腹腔注射环磷酸腺拌葡胺tM州），连续给药4周；MS组及M『组注射等量生理盐水。各组随机抽取10只小鼠行心脏超声检删肢Ⅲ织病理形态学检测；每组剩余小鼠按照5、5、4只随机分成3组，分离左心室梗死Ⅸ及非梗死M，分删行羟脯氨酸含量测定，CT（iF蛋F1表达采用Westernblot检测及CTGFmRNA、转化生长因子-β1（TGF—β1）mRNA表达采用实时定量聚合酶链反应（Real—timeecR）检测。结果MT组射血分数[EF]为（19．83±3．95）％，左室短轴缩短率（FS）为（9．07±1．90）％，均高于MI组[EF：（13．65±2.14％，FS：（6．22±1．03）％，P〈0．05]；左心室每搏输Ⅲ量（SV）MT组[（26．26±3．57）μl]优于MI组[（18．82±2．71）μl，P〈0．05]。Masson染色提示MT组胶原纤维向非梗死区心肌浸润减少，免疫组织化学CTGF阳性表达较M1组减少。MT组梗死区羟脯氨酸含量[（1388．98±86．26）μg／mg]低于MI组[（1673．12±199．97）μg／mg，P〈0．05]；非梗死区羟脯氨酸含量[（662．92±98．05）μg/mg]低于MI组[（855．84±83．30）μg／mg，P〈0．05]。Westernblot检测结果提示MT组CTGF蛋白表达量低于MI组（P〈0．05）。Real—titoePCR检测提示MT组CTGFmRNA表达量低于M1组（P〈0.05）；TGF—BlmRNA表达量在梗死Ⅸ及非梗死区较MI组差异无统计学意义（P〉0．05）。结论哈磷峻腺什可以抑制CTGF表达，降低小鼠心肌梗死后胶原纤维的表达，减轻梗死Ⅸ胶原纤维向非梗死区心肌的浸润程度，改善心脏功能。Objective To observe the regulatory effects of cyclic adenosine monophosphate （cAMP） on connective tissue growth factor （CTGF） and myocardial fibrosis. Methods 72 specific pathogen free （SPF） C57BL mice were random divided into three groups： sham operation gruup （ MS group）, myocardial infarction group （MI group） and drug treatment group （MT group）. MT group were injected meglumine adenosine eyclophosphate （MAC） by intraperitoneal for 4 weeks after 7 days postoperation. 10 mites in each group were examined by transthoracic eehocardiography and then harvested heart tissues for histopathologica] morphologic detection. The left mices were random divided into three groups, separated the infracted zone and non - infraeted zone of left ventricle, then detected the expression level of CTGF mRNA, transforming growth factor - β1 （TGF - β1 ） mRNA, CTGF protein and hydroxypro- line separately. Results The ejection fraction, fraction shortening and stroke volume in MT group were higher thanMI group [ （19.83 ±3.95）% vs. （13.65 ±2.14）%; （9.07±1.90）% vs. （6.22 ±1. 03 ） % ; （26. 26 ±3.57） μl vs. （ 18. 82 ± 2. 71 ） μl, P 〈 0. 05 ]. Masson staining examination shows the degree of collagenous fiber infiltration from infraeted zone to non - infracted zone in MT group was lower Ihan MI group. Compared with MI group, the expression level of CTGF protein, CTGF mRNA and hydroxyproline in MT group decreased after intervening by MAC （P 〈0. 05）. But the TGF -β1 mRNA ex- pression level has no statistically significant differences both in infraeted zone and non -infracted zone bepression MT group and MI group （ P 〉 0. 05 ）. Conclusion cAMP can reduce the collagenous fiber expres-

关 键 词：环磷酸腺苷 结缔组织生长因子 心肌梗死 心肌纤维化 

分 类 号：R692[医药卫生—泌尿科学]