扶正化瘀胶囊对心肌梗死大鼠心肌纤维化及TGF-β1 ／Smads信号通路的影响

Effect of Fuzheng Huayu Capsule on Myocardial Fibrosis and TGF-β_1/Smads Signal Pathway in Rats with Myocardial Infarction

目的研究扶正化瘀胶囊对心肌梗死后大鼠心肌纤维化的影响及其作用机制。方法结扎大鼠冠脉左前降支,建立急性心肌梗死(AMI)模型,模型建立24 h后,随机分为模型组、扶正化瘀组和卡托普利组,另设假手术组,只穿线不结扎。分别给予扶正化瘀胶囊0.4 g/(kg·d),卡托普利片2.25 mg/(kg·d)灌胃,模型组和假手术组给予等量去离子水,每日1次,连续8周。采用小动物超声影像系统检测大鼠心功能及结构变化;免疫组化法检测转化生长因子-β_1(TGF-β_1)的表达;Western blotting法检测smad3、samd4、smad7蛋白的表达;实时荧光定量PCR法检测TGF-β_1、smad3、smad4、smad7 mRNA表达水平。结果与假手术组比较,模型组左室射血分数(LVEF)、左室短轴缩短分数(LVFS)明显降低,室间隔舒张末期厚度(IVSTd)、室间隔收缩末期厚度(IVSTs)降低(P<0.05),左心室舒张末期内径(LVDd)、左心室收缩末期内径(LVDs)升高(P<0.05);扶正化瘀和卡托普利组可升高AMI模型大鼠IVSTs、LVEF、LVFS(P<0.05),降低模型大鼠LVDd、LVDs(P<0.05)。模型组TGF-β_1表达水平较假手术组明显升高(P<0.01),扶正化瘀胶囊和卡托普利可降低模型大鼠TGF-β_1表达水平(P<0.05)。与假手术组比较,模型组大鼠TGF-β_1、Smad3、smad4 mRNA水平明显升高(P<0.05 or P<0.01),smad7 mRNA水平明显降低(P<0.05或P<0.01);扶正化瘀胶囊和卡托普利可降低TGF-β_1、Smad3和smad4 mRNA表达水平(P<0.05),提高smad7 mRNA表达水平(P<0.05)。结论扶正化瘀胶囊可降低心肌梗死后大鼠心肌纤维化程度,改善心脏功能,其作用机制可能与调控TGF-β_1/Smads信号通路有关。

Objective To study the effect of Fuzheng Huayu capsule （FHC） on myocardial fibrosis in rats after myocardial infarction and its mechanism.Methods Acute Myocardial Infarction （AMI） model was established by ligation of left anterior descending coronary ar tery in rats.After 24 hours of modeling,rats were randomly divided into the model group, FHC group and captopril group.The rats in sham operation group threading without ligation was as control group.The rats were given Fuzheng Huayu capsule 0.4 g/（kg · d） in FHC group and captopril tablets 2.25 mg/（kg · d） in captopril group orally,once daily for 8 weeks.The rats in model group and the sham operation group were given the same amount of deionized water.After 8 weeks of treatment,the cardiac structure and function al changes of rats were measured by echocardiography.The expression of transforming growth factor β1（TGF -β1） was detected by immunohistochemistry.The expressions of smad3,samd4 and smad7 protein were detected by western blotting.The expression of TGF β1,smad3,smad4 and smad7 mRNA were detected by immunohistochemical and real time polymerase chain reaction （PCR） method. Results The left ventricular ejection fraction （LVEF）,Ieft ventricular fraction shortening （LVFS） and interventricular left ventricular septalend systolicthinkness （IVSs） in model group were significantly lower than those in the sham operation group （P 〈0.05）.LVEF, LVFS and IVSs in FHC group and captopril group were significantly higher than those in the model group （P 〈0.05）.left ventricular end diastolic dimension （LVDd） and end systolic diameter （LVDs） in FHC group and captopril group were significantly lower than those in the model group （P 〈0.05）.The expression of TGF -β1, in model group was significantly higher than that in sham operation group （P 〈0.05）.The expression of TGF -β1, were significantly decreased in FHC group and captopril group （P 〈0.05）.The mRNA expressions of TGF -β1,smad3 and smad4 in the model group were significantly higher than those in the model group （P 〈0.05）.The mRNA expression of smad7 was significantly lower than that in the model group （P 〈0.05）.The mRNA expressions of TGF -β1, smad3 and smad4 decreased while the expression of smad7 mRNA in FHC group and captopril group （P 〈0.05）. Conclusion FHC can reduce the degree of myocardial fibrosis, improve cardiac function in rats after myocardial infarction.Its mechanism may be related to the regulation of TGF- β1/smads signaling pathway.