摘要
该研究探究补阳还五汤对急性心肌梗死后血小板活化及差异基因表达的影响。将SD大鼠随机分为假手术组、模型组、阳性药阿司匹林组和补阳还五汤组,预给药14 d,灌胃剂量为补阳还五汤1.6 g·kg^(-1)·d^(-1),阿司匹林0.1 g·kg^(-1)·d^(-1)。采用冠状动脉左前降支高位结扎方法构建急性心肌梗死模型,检测指标包括心肌梗死面积、心功能、心肌组织病理、末梢血流灌注量、血小板聚集率、血小板膜糖蛋白CD62p表达、血小板转录组学及差异基因表达量。结果显示与假手术组比较,模型组射血分数和心输出量显著降低,末梢血液流量减少,血小板聚集率增加,CD62p表达增多,血小板处于活化状态。同时血清TXB2含量上升,6-keto-PGF1α含量下降。与模型组比较,补阳还五汤增加射血分数和每搏输出量,改善足底和尾部血液循环和心肌细胞排列,减少心肌梗死面积和炎性浸润,降低血小板聚集率和CD62p表达,减少血清TXB2含量,增加6-keto-PGF1α含量。血小板转录组测序结果发现,补阳还五汤调控血小板mTOR-自噬通路相关基因。采用实时定量PCR实验对差异基因表达量进行检测,补阳还五汤上调mTOR,同时下调自噬相关FUNDC1、PINK,上调p62基因表达。结果表明,补阳还五汤可调控急性心肌梗死大鼠血小板活化,改善血液循环,保护缺血心肌受损,其机制与调控血小板mTOR-自噬通路有关。
This study explored the effects of Buyang Huanwu Decoction(BYHWD)on platelet activation and differential gene expression after acute myocardial infarction(AMI).SD rats were randomly divided into a sham-operated group,a model group,a positive drug(aspirin)group,and a BYHWD group.Pre-treatment was conducted for 14 days with a daily oral dose of 1.6 g·kg^(-1)BYHWD and 0.1 g·kg^(-1)aspirin.The AMI model was established using the high ligation of the left anterior descending coronary artery method.The detection indicators included myocardial infarct size,heart function,myocardial tissue pathology,peripheral blood flow perfusion,platelet aggregation rate,platelet membrane glycoprotein CD62p expression,platelet transcriptomics,and differential gene expression.The results showed that compared with the sham-operated group,the model group showed reduced ejection fraction and cardiac output,decreased peripheral blood flow,and increased platelet aggregation rate and CD62p expression,and activated platelets.At the same time,TXB_2 content increased and 6-keto-PGF1αcontent decreased in serum.Compared with the model group,BYHWD increased ejection fraction and cardiac output,improved blood circulation in the foot and tail regions and cardiomyocytes arrangement,reduced myocardial infarct size and inflammatory infiltration,down-regulated platelet aggregation rate and CD62p expression,reduced serum TXB_2 content,and increased 6-keto-PGF1αcontent.Platelet transcriptome sequencing results revealed that BYHWD regulated mTOR-autophagy pathway-related genes in platelets.The differential gene expression levels were detected using real-time quantitative PCR.BYHWD up-regulated mTOR,down-regulated autophagy-related FUNDC1 and PINK genes,and up-regulated p62 gene expression.The results demonstrated that BYHWD could regulate platelet activation,improve blood circulation,and protect ischemic myocardium in AMI rats,and its mechanism is related to the regulation of the mTOR-autophagy pathway in platelets.
作者
高佳明
郭浩
张业昊
李玲美
辛高杰
刘子馨
尤越
陈原原
刘建勋
付建华
GAO Jia-ming;GUO Hao;ZHANG Ye-hao;LI Ling-mei;XIN Gao-jie;LIU Zi-xin;YOU Yue;CHEN Yuan-yuan;LIU Jian-xun;FU Jian-hua(Bejing Key Laboratory of Pharmacology of Chinese Materia Medica,National Clinical Research Center for Chinese Medicine Cardiology,Institute of Basic Medicine,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2023年第15期4156-4163,共8页
China Journal of Chinese Materia Medica
基金
国家自然科学基金项目(8203000944)
北京市中医药科技发展基金项目(JJ-2020-78)
中国中医科学院科技创新工程项目(CI2021A00912)
国家中医药管理局中医药创新团队及人才支持计划项目(ZYYCXTD-C-202007)。
关键词
急性心肌梗死
补阳还五汤
血小板自噬
mTOR-自噬通路
acute myocardial infarction
Buyang Huanwu Decoction
autophagy of platelets
mTOR-autophagy pathway
