阿托伐他汀对急性心肌梗死大鼠心肌炎症及纤维化反应Notch1信号通路、转化生长因子-β的影响

The effect of atorvastatin on Notch1 signal pathway and the expression of TGF-β in myocardial inflammation and fibrosis in rats with acute myocardial infarction

目的观察阿托伐他汀对急性心肌梗死(AMI)大鼠心肌炎症及纤维化反应Notch1信号通路、转化生长因子⁃β(TGF⁃β)的影响。方法选取60只健康雄性大鼠,按随机数字表法分为三组,各20只,对照组大鼠行前降支分离但未结扎,AMI组行AMI建模,但不予以药物,治疗组行AMI建模后予以阿托伐他汀者,回顾性对比分析三组心肌炎性因子、纤维化反应情况。结果AMI组、治疗组大鼠肿瘤坏死因子⁃α(TNF⁃α)、白细胞介素⁃1β(IL⁃1β)水平高于对照组[(156.27±4.52)pg/mL、(131.26±5.23)pg/mL比(24.65±2.58)pg/mL;(97.65±12.33)pg/mL、(72.37±6.72)pg/mL比(13.01±1.19)pg/mL,P<0.05],治疗组大鼠TNF⁃α、IL⁃1β低于AMI组[(131.26±5.23)pg/mL比(156.27±4.52)pg/mL;(72.37±6.72)pg/mL比(97.65±12.33)pg/mL],差异有统计学意义(P<0.05);AMI组、治疗组大鼠左室射血分数、左室短轴短缩率均低于对照组[(36.01±2.16)%、(55.82±3.25)%比(66.71±1.21)%;(18.21±2.33)%、(26.98±1.34)%比(37.83±0.84)%,P<0.05],而治疗组左室射血分数、左室短轴短缩率比AMI组高[(55.82±3.25)%比(36.01±2.16)%;(26.98±1.34)%比(18.21±2.33)%],差异有统计学意义(P<0.05);对照组大鼠心肌细胞排列整齐,心肌组织分布正常,AMI组大鼠心肌细胞减少、梗死区可见大量胶原纤维组织,治疗组改变介于对照组与AMI组之间;AMI组、治疗组Notch1蛋白、TGF⁃β水平较对照组高,治疗组Notch1蛋白、TGF⁃β水平低于AMI组,差异有统计学意义(P<0.05)。结论阿托伐他汀可通过抑制Notch1信号通路、TGF⁃β改善AMI大鼠心肌炎症、纤维化反应。

Objective To observe the effect of atorvastatin on Notch1 signal pathway and the expression of transforming growth factor⁃β(TGF⁃β)in myocardial inflammation and fibrosis in rats with acute myocardial infarction(AMI).Methods Sixty healthy male rats were randomly selected and divided into three groups,with 20 cases in each group.The control group was separated by anterior descending branch but not ligated,the AMI models were established but no drug was given in the AMI group,the treatment group was treated with Atorvastatin after the AMI was modeled.The inflammatory cytokines and fibrosis of the three groups were retrospectively compared.Results The level of Tumor Necrosis Factor⁃α(TNF⁃α)and Interleukin⁃1β(IL⁃1β)in AMI Group and treatment group were higher than those in the control group[(156.27±4.52)pg/mL,(131.26±5.23)pg/mL vs.(24.65±2.58)pg/mL;(97.65±12.33)pg/mL,(72.37±6.72)pg/mL vs.(13.01±1.19)pg/mL,P<0.05],and the TNF⁃αand IL⁃1βin the treatment group were lower than those in the AMI Group[(131.26±5.23)pg/mL vs.(156.27±4.52)pg/mL;(72.37±6.72)pg/mL vs.(97.65±12.33)pg/mL].The differences were statistically significant(P<0.05).Left ventricular ejection fraction,left ventricular short axis shortening rate in AMI group and treatment group were lower than those in the control group[(36.01±2.16)%,(55.82±3.25)%vs.(66.71±1.21)%;(18.21±2.33)%,(26.98±1.34)%vs.(37.83±0.84)%,P<0.05],while those in the treatment group were higher than those of AMI group[(55.82±3.25)%vs.(36.01±2.16)%;(26.98±1.34)%vs.(18.21±2.33)%],the differences were statistically significant(P<0.05).The myocardial cells in the control group were arranged neatly and the myocardium was distributed normally.The myocardial cells in AMI group were reduced and the collagen fibrous was observed in the infarct area.The change of the treatment group was between the control group and the AMI Group.Notch1 protein,TGF⁃βlevel in the AMI Group and the treatment group were higher than those in the control group,while Notch1 protein,TGF⁃βlevel in the treatment group were lower than those in theAMI group,with statistically significant differences(P<0.05).Conclusion Atorvastatin can improve myocardial inflammation andfibrosis of AMI rats by inhibiting Notch1 signaling pathway and TGF⁃β.