摘要
目的研究丹皮酚对心肌梗死(MI)兔心肌TLR4及下游炎性因子肿瘤坏死因子(TNF)-α基因表达的影响及其与心室重构的关系,探讨丹皮酚改善MI后心室重构的机制。方法采用结扎冠状动脉左室支建立心肌梗死模型(假手术组开胸后,在相应部位挂线不结扎)。术后24 h将存活兔分为4组:假手术组、MI组、MI+丹皮酚低剂量组和MI+丹皮酚高剂量组。各组饲养4 w后进行血流动力学检测,测量体质量、左、右心室重量,采用BL-420生物机能试验系统检测左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室压力最大上升和下降速率(±LV dp/dtmax);采用RT-PCR法检测TLR4、TNF-αmRNA的表达。结果与假手术组比较,MI组右室重量/体质量(RVW/BW)、左室重量/体质量(LVW/BW)、LVEDP均显著升高,±LV dp/dtmax显著下降(P<0.01或P<0.05),TLR4、TNF-αmRNA的表达均明显增加(P<0.01),丹皮酚干预组与MI组比较,RVW/BW、LVW/BW、LVEDP均显著降低(P<0.05或P<0.01),±LV dp/dtmax显著提高(P<0.05或P<0.01),TLR4、TNF-αmRNA的表达均明显减少(P<0.05或P<0.01)。结论丹皮酚可通过抑制TLR4信号通路下调下游炎症因子TNF-α的基因表达,改善MI后的心室重构。
Objective To explore the effects of paeonol on TLR4, tumor necrosis factor （TNF） -α expression in myocardium and its relation to ventricular remodeling in rabbit with myocardial infarction （MI） and investigate paeonol improving the mechanism of ventricular remodeling after myocardial infarction. Methods Models of MI were produced by ligation of left anterior descending coronary artery, after 24 hours, the rabbits were randomly divided into MI, low dose of paeonol （75 mg/kg）, high dose of paeoNol （ 150 mg/kg）, sham groups. The rabbits were killed at 4 weeks after operation and hemodynamic parameters were examined. Expressions of TLR4, TNF-α mRNA were detected by RT-PCR. Results Compared with the sham group, RVW/BW, LVW/BW and LVEDP were increased significantly （P 〈 0. 05, P 〈 0. 01 ） ; LVSP, ± LV dp/dtmax were decreased significantly （P 〈 0. 05, P 〈 0. 01 ）, and expressions of TLR4 and TNF-α mRNA were enhanced significantly in the MI group（P 〈0. 01 ）. Compared with the MI group, RVW/BW, LVW/BW and LVEDP were decreased significantly （P 〈0.05, P 〈0. 01 ） ,LVSP, ± LV dp/dtmax were increased significantly （P 〈0.05, P 〈0. 01 ） and expressions of TLR4, TNF-α mRNA were declined significantly in paeonol groups （ P 〈 0. 05, P 〈 0. 01 ）. Conclusions Paeonol reduces expression of TNF-α mRNA via inhibiting the pathway of TLR4 signaling and improving ventricular remodeling after MI.
出处
《中国老年学杂志》
CAS
CSCD
北大核心
2012年第21期4690-4692,共3页
Chinese Journal of Gerontology
基金
河北省卫生厅课题(No.20100137)
