摘要
目的:探讨隐丹参酮(CRY)调节Shh/Gli1信号通路对急性心肌梗死(AMI)大鼠心肌损伤的影响。方法:通过开胸及结扎左前降支建立AMI大鼠模型,并以仅开胸不结扎的大鼠为对照组,将AMI大鼠随机分为AMI组、不同剂量(5、15、45 mg/kg)的CRY组、CRY+环巴胺[Cyclopamine(20μg/kg)]组,各组按照相应剂量的药物进行干预,结束后检测左心室射血分数(LVEF)、左心室舒张末期内径(LVESD);ELISA检测心肌梗死指标-肌酸激酶同工酶(CK-MB)、N末端B型利钠肽前体(NT-pro-BNP)水平;TTC、HE、免疫组织化学、TUNEL染色法分别检测大鼠心肌梗死、组织病理学、血小板内皮细胞粘附分子(CD31)变化及细胞凋亡变化;Western blot检测心肌组织Shh/Gli1相关蛋白表达。结果:与对照组比较,AMI组LVESD、血清中NT-pro-BNP、CK-MB、心肌梗死面积、CD31表达、心肌细胞凋亡明显增加,LVEF、心肌组织中Shh、Gli1蛋白表达则降低(均P<0.05);与AMI组比较,加入不同剂量的CRY则降低了LVESD、血清中NT-pro-BNP、CK-MB、心肌梗死面积、心肌细胞凋亡,提高了LVEF、心肌组织中CD31表达、Shh、Gli1蛋白表达,组间比较存在统计学差异(均P<0.05);与45 mg/kg CRY组比较,45 mg/kg CRY联合Cyclopamine则升高了LVESD、血清中NT-pro-BNP、CK-MB、心肌梗死面积、心肌细胞凋亡,降低了LVEF、心肌组织中CD31表达及Shh、Gli1蛋白表达(均P<0.05)。结论:CRY通过调节Shh/Gli1信号通路改善AMI大鼠心肌损伤。
Objective:To investigate the effect of cryptotanshinone(CRY)on myocardial injury in acute myocardial infarction(AMI)rats by regulating the Shh/Gli1 signaling pathway.Methods:AMI rat model was established by thoracotomy and ligation of the left anterior descending branch.Rats with only thoracotomy but not ligation were used as the control group.AMI rats were randomly separated into AMI group,different doses CRY groups(5,15,45 mg/kg),and CRY+Cyclopamine(20μg/kg)group.Each group was intervened with the corresponding dose of medication.After drug intervention,left ventricular ejection fraction(LVEF)and left ventricular end diastolic diameter(LVESD)were measured.ELISA was applied to detect levels of creatine kinase isoenzyme(CK-MB)and N-terminal pro-B type natriuretic peptide(NT-pro-BNP).TTC,HE,immunohistochemistry,and TUNEL staining methods were applied to detect changes in myocardial infarction,histopathology,platelet endothelial cell adhesion molecule(CD31),and cell apoptosis in rats.Western blot was applied to detect the expression of Shh/Gli1 related proteins in myocardial tissue.Results:Compared with the control group,the AMI group showed a obvious increase in LVESD,serum NT-pro-BNP,CK-MB,myocardial infarction area,CD31 expression,and myocardial cell apoptosis,and a obvious decrease in LVEF,and Shh and Gli1 protein expression in myocardial tissue(all P<0.05).Compared with the AMI group,different doses of CRY reduced LVESD,serum NT-pro-BNP,CK-MB,myocardial infarction area,and myocardial cell apoptosis,increased LVEF,CD31 expression,and Shh and Gli1 protein expression in myocardial tissue,there were differences between groups(all P<0.05).Compared with the 45 mg/kg CRY group,the combination of 45 mg/kg CRY and Cyclopamine increased LVESD,serum NT-pro-BNP,CK-MB,myocardial infarction area,and myocardial cell apoptosis,reduced LVEF,CD31 expression,and Shh and Gli1 protein expression in myocardial tissue(all P<0.05).Conclusion:CRY improves myocardial injury in AMI rats by regulating the Shh/Gli1 signaling pathway.
作者
王琮翰
黄毅
WANG Conghan;HUANG Yi(Department of Cardiovascular Medicine,Xi’an People’s Hospital,Xi’an 710004,China)
出处
《陕西医学杂志》
CAS
2024年第10期1299-1304,1308,共7页
Shaanxi Medical Journal
基金
国家自然科学基金资助项目(81700447)。
