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Anti-inflammatory activities of hepatocyte growth factor in post-ischemic heart failure.
Acta Pharmacologica Sinica ( IF 6.9 ) Pub Date : 2018-Oct-01 , DOI: 10.1038/aps.2018.14
Shu-ling Rong , Xiao-lin Wang , Yi-cheng Wang , Huan Wu , Xue-dong Zhou , Ze-kun Wang , Yu-chuan Wang , Cun-shui Xue , Bao Li , Dong-lai Gao

Hepatocyte growth factor (HGF) alleviates acute and chronic inflammation in experimental inflammatory bowel disease, glomerulonephritis, and airway inflammation. However, the anti-inflammatory effects of HGF on myocardial infarction are not defined. The current study assessed the anti-inflammatory effects of HGF in post-ischemic heart failure. The left anterior descending coronary artery was ligated in rats, and adenovirus containing human HGF (Ad-HGF) or control virus (Ad-GFP) was administered intramyocardially. The quantity of proinflammatory cytokines secreted by cardiomyocytes, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, was evaluated. Cardiac function and LV remodeling were assessed using echocardiography and collagen deposition, respectively. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) four weeks after injection were significantly increased in Ad-HGF-treated animals compared to the Ad-GFP group. HGF gene therapy improved ventricular geometry with a significantly decreased left ventricular end-diastolic diameter (LVEDD) and markedly reduced myocardial collagen deposition. Treatment with Ad-HGF significantly decreased the mRNA levels of TNF-α, IL-6, and IL-1β in the non-infarcted region four weeks after injection. Changes of the TNF-α, IL-6, and IL-1β levels in the non-infarcted region positively correlated with the LVEDD 4 weeks after infarction. Treatment of acute myocardial infarction (AMI) with Ad-HGF in the early stage of MI reduced the pro-inflammatory cytokine levels and preserved cardiac function. These findings indicated that Ad-HGF gene therapy alleviated ventricular remodeling after infarction by reducing inflammation.

中文翻译:

肝细胞生长因子在缺血性心力衰竭中的抗炎活性。

肝细胞生长因子(HGF)可缓解实验性炎症性肠病,肾小球肾炎和气道炎症中的急性和慢性炎症。但是,HGF对心肌梗塞的抗炎作用尚未明确。目前的研究评估了HGF在缺血性心力衰竭中的抗炎作用。在大鼠中结扎左前降支冠状动脉,并在心肌内施用含有人HGF(Ad-HGF)或对照病毒(Ad-GFP)的腺病毒。评估了心肌细胞分泌的促炎细胞因子的量,例如肿瘤坏死因子-α(TNF-α),白介素-6(IL-6)和IL-1β。使用超声心动图和胶原蛋白沉积分别评估心脏功能和左室重塑。与Ad-GFP组相比,注射Ad-HGF的动物在注射后四周左心室缩短(LVFS)和左室射血分数(LVEF)显着增加。HGF基因疗法改善了心室的几何形状,并显着降低了左心室舒张末期直径(LVEDD),并显着减少了心肌胶原沉积。Ad-HGF的治疗可在注射后四周显着降低非梗塞区域TNF-α,IL-6和IL-1β的mRNA水平。非梗死区域中TNF-α,IL-6和IL-1β的变化与梗死后4周的LVEDD呈正相关。MI早期用Ad-HGF治疗急性心肌梗塞(AMI)可降低促炎性细胞因子水平,并保留心脏功能。
更新日期:2018-05-24
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