CAJ | 학술논문

目的探讨替米沙坦(telmisartan)对大鼠急性心肌梗死(AMI)所致炎症反应及纤维化的影响及分子机制.方法采用结扎左冠状动脉前降支方法造成大鼠AMI模型,存活大鼠分为心肌梗死组(AMI组)及替米沙坦治疗组(Telmisartan组),另设假手术组(Sham组),n=8.治疗组每天给予替米沙坦5 mg/kg灌胃处理,模型组不予治疗,假手术组不做结扎处理.4周后取材,测量各组大鼠全心、左心室重量及重量指数,HE及Masson染色检测心肌梗死及炎症反应情况,EⅡSA检测血清中C反应蛋白(CRP)、肿瘤坏死因子α(TNFα)、单核细胞趋化蛋白-l(MCP-1)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)含量,RT-PCR检测转化生长因子β1(TGFβ1)、Ⅰ型胶原、Ⅲ型胶原、基质金属蛋白酶-9(MMP9)表达变化,WB检测核因子NF-κB、TGFβ1、Ⅰ型胶原、Ⅲ型胶原、MMP9表达差异.结果与Sham组相比,AMI组大鼠心肌组织病理变化明显,血清中CRP[(472±132) ng/ml比(104±28) ng/m]]、TNFα[(229±41)pg/ml比(18±5)pg/ml]、MCP-1 [(558±116) pg/ml比(158±20) pg/ml]、IL-6[(404±63) pg/ml比(21 ±4)pg/ml]、IL-1β[(625±145) pg/ml比(189±34)pg/ml]含量增加(P＜0.05),RT-PCR检测结果表明TGFβ1、Ⅰ型胶原、Ⅲ型胶原、MMP9表达水平上调显著,Western印迹结果与之一致,同时检测NF-κB受到显著激活(P＜0.05),而Telmisartan组与AMI组比较,上述指标变化均有所减弱(P＜0.05).结论替米沙坦可能通过对NF-κB及TGFβ信号通路的调节作用影响大鼠急性心肌梗死后的炎症反应及心肌纤维化过程.
목적 탐토체미사탄(telmisartan)대대서급성심기경사(AMI)소치염증반응급섬유화적영향급분자궤제.방법 채용결찰좌관상동맥전강지방법조성대서AMI모형,존활대서분위심기경사조(AMI조)급체미사탄치료조(Telmisartan조),령설가수술조(Sham조),n=8.치료조매천급여체미사탄5 mg/kg관위처리,모형조불여치료,가수술조불주결찰처리.4주후취재,측량각조대서전심、좌심실중량급중량지수,HE급Masson염색검측심기경사급염증반응정황,EⅡSA검측혈청중C반응단백(CRP)、종류배사인자α(TNFα)、단핵세포추화단백-l(MCP-1)、백세포개소-6(IL-6)、백세포개소-1β(IL-1β)함량,RT-PCR검측전화생장인자β1(TGFβ1)、Ⅰ형효원、Ⅲ형효원、기질금속단백매-9(MMP9)표체변화,WB검측핵인자NF-κB、TGFβ1、Ⅰ형효원、Ⅲ형효원、MMP9표체차이.결과 여Sham조상비,AMI조대서심기조직병리변화명현,혈청중CRP[(472±132) ng/ml비(104±28) ng/m]]、TNFα[(229±41)pg/ml비(18±5)pg/ml]、MCP-1 [(558±116) pg/ml비(158±20) pg/ml]、IL-6[(404±63) pg/ml비(21 ±4)pg/ml]、IL-1β[(625±145) pg/ml비(189±34)pg/ml]함량증가(P＜0.05),RT-PCR검측결과표명TGFβ1、Ⅰ형효원、Ⅲ형효원、MMP9표체수평상조현저,Western인적결과여지일치,동시검측NF-κB수도현저격활(P＜0.05),이Telmisartan조여AMI조비교,상술지표변화균유소감약(P＜0.05).결론 체미사탄가능통과대NF-κB급TGFβ신호통로적조절작용영향대서급성심기경사후적염증반응급심기섬유화과정.
Objective To explore the protection mechanisms of telmisartan on inflammation and fibrosis after myocardial infarction in rats.Methods The model of acute myocardial infarction (AMI) was established by ligating left anterior descending coronary artery.The surviving rats were divided into AMI (AMI) and telmisartan treatment (telmisartan) groups.And another sham operation group (sham) was designated (n =8).At the end of study,total heart weight (THW),left ventricular weight (LVW) and weight index were measured; myocardial infarction and inflammatory reactions detected by hematoxylin and eosin and Masson staining; the serum levels of C-reactive protein (CRP),tumor necrosis factor-alpha (TNFα),monocyte chemotactic protein-1 (MCP-1),interleukin-6 (IL-6) and interleukin-1 beta (IL-1β) by enzyme-linked immunosorbent assay (ELISA) ; the levels of transforming growth factor 1 (TGFβ1),collagen Ⅰ,collagen Ⅲ and MMP9 mRNA in myocardial tissue by reverse transcription-polymerase chain reaction (RT-PCR); the expressions of TGFβ1,collagen Ⅰ,collagen Ⅲ,matrix metallopeptidase 9 (MMP9) and nuclear factor-kappa B (NF-κB) by Western blot.Results Compared with sham group,significant pathological changes of myocardium occurred in AMI group.The serum levels of CRP [(472 ± 132) vs (104±28) ng/ml],TNFα [(229±41) vs (18 ±5) pg/ml],MCP-1[(558 ±116) vs (158± 20) pg/ml],IL-6 [(404 ±63) vs (21 ± 4) pg/ml] and IL-1β [(625 ± 145) vs (189 ± 34) pg/ml] increased (P ＜ 0.05).RT-PCR analysis showed that the expression levels of TGFβ1,collagen Ⅰ,collagen Ⅲ and MMP9 increased significantly.The results of Western blot were consistent and NF-κB was activated significantly (P ＜ 0.05).Compared with AMI group,the above-mentioned indicators decreased obviously in telmisartan group (P ＜ 0.05).Conclusion Telmisartan may regulate inflammation and myocardial fibrosis after acute myocardial infarction by signaling pathways of NF-κB and TGFβ in rats.