摘要
目的基于PI3K/AKT信号通路探讨升陷益心颗粒对心肌梗死大鼠心室重塑的影响及作用机制。方法60只SD大鼠随机取6只作为对照组,其余54只为造模组,分别进行假手术和左冠状动脉前降支结扎,将成模大鼠分为模型组、升陷益心颗粒组、740Y-P组、升陷益心颗粒+740Y-P组,分别予相应干预,连续28 d。超声心动图检测大鼠左心室射血分数(LVEF)、左心室短轴缩短率(LVFS),计算左心室肥厚指数,HE、Masson染色观察心肌组织形态,Western blot检测心肌组织p-PI3K、PI3K、p-AKT、AKT蛋白表达,RT-qPCR检测心肌组织Ⅰ型胶原(Col1)、Ⅲ型胶原(Col3)mRNA表达,ELISA检测血清心肌肌钙蛋白T(cTnT)、肌酸激酶同工酶-MB(CK-MB)、Col1、Col3含量。结果与对照组比较,模型组大鼠LVEF、LVFS显著降低(P<0.01),左心室肥厚指数升高(P<0.01);心肌细胞排列紊乱,部分细胞坏死、破裂、胞核溶解,有明显中性粒细胞浸润,胶原纤维增多,心肌组织p-PI3K、p-AKT蛋白表达显著升高(P<0.05),Col1、Col3mRNA表达显著升高(P<0.01);血清cTnT、CK-MB、Col1、Col3含量显著升高(P<0.05,P<0.01)。与模型组比较,升陷益心颗粒组大鼠LVEF、LVFS显著升高(P<0.05,P<0.01),左心室肥厚指数降低(P<0.05);心肌细胞坏死、中性粒细胞浸润减少,胶原纤维沉积减少,心肌组织p-PI3K、p-AKT蛋白表达显著降低(P<0.05),Col1、Col3 mRNA表达显著降低(P<0.01);血清cTnT、CK-MB、Col1、Col3含量显著降低(P<0.05,P<0.01)。740Y-P组LVEF、LVFS显著降低(P<0.01),左心室肥厚指数升高(P<0.05);大量心肌细胞坏死破裂、纤维撕裂明显,形成较多瘢痕组织,心肌组织p-PI3K、p-AKT蛋白表达显著升高(P<0.05),Col1、Col3 mRNA表达显著升高(P<0.01);血清cTnT、CK-MB、Col1、Col3含量显著升高(P<0.05,P<0.01)。升陷益心颗粒+740Y-P可改善740Y-P对心脏的损伤。结论升陷益心颗粒可通过PI3K/AKT信号通路改善心肌梗死大鼠心室重塑,减少心肌纤维化,提高心功能。
Objective To explore the effects and mechanism of Shengxian Yixin Granules in treating ventricular remodeling in rats with myocardial infarction based on the PI3K/AKT signaling pathway.Methods A total of 60 SD rats were randomly selected six rats as the control group,and the remaining 54 rats were used as the modeling group.Sham-operation and left anterior descending coronary artery ligation were performed respectively.The modeled rats were divided into model group,Shengxian Yixin Granules group,740Y-P group and Shengxian Yixin Granules+740Y-P group,and were given corresponding intervention for 28 days.Left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were measured by echocardiography,and left ventricular hypertrophy index was calculated,the myocardial morphology was observed by HE and Masson staining,and the protein expressions of p-PI3K,PI3K,p-AKT and AKT were detected by Western blot,RT-qPCR was used to detect the mRNA expressions of typeⅠcollagen(Col1)and typeⅢcollagen(Col3),and ELISA was used to detect the contents of serum cardiac troponin T(cTnT),creatine kinase-MB(CK-MB),Col1 and Col3.Results Compared with the control group,the LVEF and LVFS in the model group significantly decreased(P<0.01),the left ventricular hypertrophy index increased(P<0.01);myocardial cells were arranged disorderly,some cells were necrotic,ruptured and their nuclei were dissolved,with obvious neutrophil infiltration,the collagen fiber significantly increased,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly increased(P<0.05),and the mRNA expression of Col1 and Col3 significantly increased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly increased(P<0.05,P<0.01).Compared with the model group,the LVEF and LVFS in Shengxian Yixin Granules group significantly improved(P<0.05,P<0.01),and left ventricular hypertrophy index decreased(P<0.05);myocardial necrosis,neutrophil infiltration and collagen fiber deposition were reduced,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly decreased(P<0.05),and the mRNA expressions of Col1 and Col3 significantly decreased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly decreased(P<0.05,P<0.01).LVEF and LVFS in 740Y-P group significantly decreased(P<0.01),and left ventricular hypertrophy index increased(P<0.05);a large number of myocardial cells were necrotic and ruptured,fibers were torn obviously,and many scar tissues were formed,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly increased(P<0.05),the mRNA expressions of Col1 and Col3 significantly increased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly increased(P<0.05,P<0.01).Shengxian Yixin Granules+740Y-P could improve the damage of 740Y-P to the heart.Conclusion Shengxian Yixin Granules can improve ventricular remodeling in rats with heart failure,reduce myocardial fibrosis,and improve cardiac function through the PI3K/AKT signaling pathway.
作者
张敏
邢作英
董政委
邱伯雍
郑佳
胡宇才
司春婴
王永霞
ZHANG Min;XING Zuoying;DONG Zhengwei;QIU Boyong;ZHENG Jia;HU Yucai;SI Chunying;WANG Yongxia(The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China;Henan University of Chinese Medicine,Zhengzhou 450000,China)
出处
《中国中医药信息杂志》
2025年第9期98-104,共7页
Chinese Journal of Information on Traditional Chinese Medicine
基金
国家自然科学基金(82074229)
中国博士后科学基金(2023M741092)
河南中医药大学青年骨干科技创新培育项目(HSRP-DFCTCM-2023-7-06)
中原科技创新领军人才项目(244200510002)
河南省科技研发计划联合基金(优势学科培育类)项目(232301420021)。
