积雪草酸通过SIRT3/β-catenin/PPARγ信号通路影响急性心肌梗死模型大鼠血管新生及心室重构

Asiatic acid affects angiogenesis and ventricular remodeling in rats with acute myocardial infarction by SIRT3/β-catenin/PPARγ signaling pathway

目的 基于急性心肌梗死(AMI)发生发展过程中沉默信息调节因子3(SIRT3)/β-连环蛋白(β-catenin)/过氧化物酶体增殖物激活受体γ(PPARγ)信号通路的变化,探讨积雪草酸(AA)对AMI模型大鼠血管新生及心室重构的影响及作用机制。方法 将72只SD大鼠按照体重均衡的原则随机分组,其中12只为空白对照组,剩余的大鼠制备AMI模型。造模成功后将大鼠采用随机数字表法分为5组:模型组、阳性对照组、AA高剂量组、AA中剂量组和AA低剂量组,每组12只。空白对照组和模型组给予生理盐水,阳性对照组给予阿司匹林肠溶片,药物干预组给予不同剂量的AA。28天后采用多普勒超声仪检测各组大鼠的血管新生和心室重构情况。采用逆转录-聚合酶链反应检测大鼠心肌SIRT3、β-catenin和PPARγmRNA表达。采用酶联免疫吸附法检测各组大鼠白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、核因子κB(NF-κB)等炎症因子水平。结果 与空白对照组相比,模型组大鼠的心脏功能变差,微血管密度(MVD)增加,心肌SIRT3、β-catenin、PPARγmRNA表达和血清IL-6、TNF-α、NF-κB水平均升高(P<0.05);与模型组相比,各给药组大鼠的心脏功能明显改善,MVD增加,心肌SIRT3、β-catenin、PPARγmRNA表达均增加,血清IL-6、TNF-α、NF-κB水平降低(P<0.05);与阳性对照组相比,AA高、中、低剂量组大鼠的心脏功能改善,MVD增加,心肌SIRT3、β-catenin、PPARγmRNA表达均升高,血清IL-6、TNF-α、NF-κB水平降低(P<0.05)。结论 积雪草酸抑制大鼠梗死心肌SIRT3/β-catenin/PPARγ信号通路,对AMI大鼠心肌组织具有一定的保护作用。

Aim To investigate the effect of asiatic acid( AA) on angiogenesis and ventricular remodeling in acute myocardial infarction( AMI) rats and its mechanism,based on the changes of silent information regulator 3( SIRT3)/β-catenin/peroxisome proliferator activated receptor γ( PPARγ) signaling pathway during the development of AMI.Methods A total of 72 SD rats was randomly divided into groups according to the principle of weight balance. 12 of them were in the blank control group,and the AMI model was made in the remaining rats. After successful modeling,according to the random number table method rats were randomly divided into 5 groups: model group,positive control group,AA high dose group,AA medium dose group and AA low dose group,12 rats in each group. The blank control group and the model group were given normal saline,the positive control group was given aspirin enteric-coated tablets,and the drug intervention group was given different doses of AA. 28 days later,Doppler ultrasound was used to detect angiogenesis and ventricular remodeling in each group. Reverse transcription polymerase chain reaction( RT-PCR) was used to detect the expressions of SIRT3,β-catenin and PPARγ mRNA in rat myocardium. The levels of inflammatory factors interleukin-6( IL-6),tumor necrosis factor α( TNF-α),nuclear factor κB( NF-κB) were detected by enzyme linked immunosorbent assay.Results Compared with the blank control group,the cardiac function was worse,the microvascular density( MVD) increased,the expressions of SIRT3,β-catenin,PPARγ mRNA and the serum levels of IL-6,TNF-α,NF-κB were all increased,in the model group( P<0.05). Compared with the model group,the cardiac function was obviously improved,MVD increased,the expressions of SIRT3,β-catenin and PPARγ mRNA increased,and the levels of serum IL-6,TNF-αand NF-κB decreased,in each AA drug adiministration group( P<0.05). Compared with the positive control group,the cardiac function was improved,the MVD increased,the expressions of SIRT3,β-catenin and PPARγ mRNA in the myocardium increased,and the levels of serum IL-6,TNF-α and NF-κB decreased,in the high,middle and low dose groups of AA( P < 0. 05). Conclusion Asiatic acid inhibits SIRT3/β-catenin/PPARγ signaling pathway in infarcted myocardium of rats,and has protective effect on myocardial tissue of AMI rats.