Song Zhanchun, Bai Jinghui, Zhang Lili, Sun Xiaodong, Zhang Min, Zheng Hong, Zhang Jian
Department of Cardiology, Fushun Central Hospital, Fushun 113006, China. Email:
Zhonghua Yi Xue Za Zhi. 2014 Sep 9;94(33):2628-33.
To explore the protection mechanisms of telmisartan on inflammation and fibrosis after myocardial infarction in rats.
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.
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).
Telmisartan may regulate inflammation and myocardial fibrosis after acute myocardial infarction by signaling pathways of NF-κB and TGFβ in rats.
探讨替米沙坦对大鼠心肌梗死后炎症和纤维化的保护机制。
通过结扎左冠状动脉前降支建立急性心肌梗死（AMI）模型。将存活的大鼠分为AMI组（AMI）和替米沙坦治疗组（替米沙坦）。另设假手术组（假手术）（n = 8）。研究结束时，测量全心重量（THW）、左心室重量（LVW）和重量指数；通过苏木精-伊红染色和Masson染色检测心肌梗死和炎症反应；采用酶联免疫吸附测定（ELISA）检测血清C反应蛋白（CRP）、肿瘤坏死因子-α（TNFα）、单核细胞趋化蛋白-1（MCP-1）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）水平；通过逆转录-聚合酶链反应（RT-PCR）检测心肌组织中转化生长因子1（TGFβ1）、I型胶原、III型胶原和基质金属蛋白酶9（MMP9）mRNA水平；通过蛋白质免疫印迹法检测TGFβ1、I型胶原、III型胶原、基质金属蛋白酶9（MMP9）和核因子-κB（NF-κB）的表达。
与假手术组相比，AMI组心肌出现明显病理改变。血清CRP水平[（472±132）对（104±28）ng/ml]、TNFα水平[（229±41）对（18±5）pg/ml]、MCP-1水平[（558±116）对（158±20）pg/ml]、IL-6水平[（404±63）对（21±4）pg/ml]和IL-1β水平[（625±145）对（189±34）pg/ml]升高（P<0.05）。RT-PCR分析显示，TGFβ1、I型胶原、III型胶原和MMP9表达水平显著升高。蛋白质免疫印迹法结果一致，且NF-κB被显著激活（P<0.05）。与AMI组相比，替米沙坦组上述指标明显降低（P<0.05）。
替米沙坦可能通过大鼠体内NF-κB和TGFβ信号通路调节急性心肌梗死后的炎症和心肌纤维化。
