川芎嗪治疗急性心肌梗死大鼠的作用机制研究  

Protective effects and mechanisms of tetramethylpyrazine in the treatment of acute myocardial infarction in rats

作　　者：孙达[1] 常静[1] 林莉莉[1] SUN Da;CHANG Jing;LIN Li-li(Department of Pharmacy,Wuxi Higher Health Vocational Technology School,Wuxi 214028 Jiangsu Province,China)

机构地区：[1]无锡卫生高等职业技术学校药学系

出　　处：《中国临床药理学杂志》2019年第24期3208-3212,共5页The Chinese Journal of Clinical Pharmacology

基　　金：无锡市医院管理中心面上基金资助项目(YGZXM1409)

摘　　要：目的 探索川芎嗪对急性心肌梗死(AMI)大鼠的治疗作用及其调控机制。方法 用冠状动脉左前降支结扎方法构建AMI大鼠模型。将AMI模型大鼠随机分为模型组和低、中、高剂量实验组,每组10只。另取10只健康大鼠除不结扎冠状动脉外,其余手术方法同模型组,作为假手术组。造模成功后24 h,低、中、高剂量实验组分别给予10,20和50 mg·kg-1川芎嗪注射液,qd,腹腔注射;假手术组和模型组均给予等量0. 9%Na Cl溶液。连续干预4周后,检测各组大鼠的心功能相关指标、心肌损伤指标、心肌细胞凋亡及磷酸肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/低氧诱导因子-1α(HIF-1α)信号通路激活情况。结果 低、中、高剂量实验组和假手术组、模型组的左心室射血分数分别为(46. 02±3. 99)%,(53. 55±4. 10)%,(60. 01±4. 89)%,(78. 33±5. 92)%和(34. 76±3. 01)%,左室内压力变化最大上升速率分别为(4435. 60±250. 34),(4611. 07±300. 23),(5232. 76±352. 90),(6233. 56±344. 12)和(3839. 12±233. 30) mm Hg·s-1,左室内压力变化最大下降速率分别为(3124. 41±210. 42),(3252. 04±209. 11),(3477. 90±225. 82),(4081. 23±255. 12)和(2690. 34±186. 23) mm Hg·s-1,磷酸肌酸激酶同工酶分别为(97. 11±7. 68),(72. 04±7. 21),(51. 10±3. 88),(33. 20±2. 92)和(118. 34±11. 77) k U·L-1,心肌细胞凋亡率分别为(29. 43±2. 82)%,(21. 80±2. 19)%,(12. 09±1. 39)%,(3. 22±0. 22)%和(35. 23±3. 09)%,p-AKT的相对表达分别为(35. 21±4. 83)%,(51. 89±7. 12)%,(88. 60±11. 12)%,(122. 43±11. 22)%和(13. 89±1. 83)%,HIF-1α的相对表达(112. 04±15. 32)%,(72. 44±10. 39)%,(38. 41±6. 22)%,(87. 04±5. 12)%和(168. 88±12. 44)%,模型组的上述指标与低、中、高剂量实验组和假手术组比较,差异均有统计学意义(P <0. 05,P <0. 01)。结论 川芎嗪能够改善大鼠急性心肌梗死后的心功能损伤和心肌细胞凋亡,其作用机制可能与激活PI3K/AKT/HIF-1α信号通路有关。Objective To explore the protective effects of tetrameth-(TMP)on acute myocardial infarction(AMI)rats and underlying molecular mechanisms.Methods The rat models of AMI were established by the ligation of anterior descending branch of left coronary artery.AMI rats were randomly divided into model group and experimental-L,experimental-M and experimental-H groups.The other 10 healthy rats were treated with the same operation method as the model rats except that the coronary artery was not ligated,and the same as sham-operation group.After the successful establishment of AMI model for 24 hours,the rats in experimental-L,experimental-M and experimental-H groups were given 10,20 and 50 mg·kg-1 TMP,intraperitoneal injection,qd.Sham-operation group and model group were given 0.9%NaCl.After 4 weeks of continuous intervention,the indexes of cardiac function,myocardial injury,cardiomyocyte apoptosis and the activation of phosphoinositide 3-kinase(PI3 K)/protein kinase B(Akt)/hypoxia inducible factor-1α(HIF-1α)signaling pathway were detected.Results The left ventricular ejection fraction of experimental-L,experimental-M and experimental-H groups,sham-operation group and model group were(46.02±3.99)%,(53.55±4.10)%,(60.01±4.89)%,(78.33±5.92)%and(34.76±3.01)%,the maximal rates of the increase of left ventricular pressure were(4435.60±250.34),(4611.07±300.23),(5232.76±352.90),(6233.56±344.12)and(3839.12±233.30)mmHg·s-1,the maximal rates of the decrease of left ventricular pressure were(3124.41±210.42),(3252.04±209.11),(3477.90±225.82),(4081.23±255.12)and(2690.34±186.23)mmHg·s-1,the level of creatine kinase MB isoenzyme were(97.11±7.68),(72.04±7.21),(51.10±3.88),(33.20±2.92)and(118.34±11.77)kU·L-1,the cardiomyocyte apoptosis rates were(29.43±2.82)%,(21.80±2.19)%,(12.09±1.39)%,(3.22±0.22)%and(35.23±3.09)%,the relative expression of p-AKT were(35.21±4.83)%,(51.89±7.12)%,(88.60±11.12)%,(122.43±11.22)%and(13.89±1.83)%,the relative expression of HIF-1αwere(112.04±15.32)%,(72.44±10.39)%,(38.41±6.

关 键 词：川芎嗪 急性心肌梗死 心功能 细胞凋亡 

分 类 号：R28[医药卫生—中药学]