川芎嗪对异丙肾上腺素诱导的小鼠急性心肌缺血的保护作用

Protective effects of tetramethylpyrazine on isoprenaline-induced acute myocardial ischemia

目的研究川芎嗪(TMP)对异丙肾上腺素(ISO)诱导的小鼠急性心肌缺血的保护作用及其机制。方法小鼠按照体重随机分为正常组(生理盐水10mg·kg^(-1)·d^(-1))、模型组(ISO 3 mg·kg^(-1)·d^(-1),连续3 d每天1次)、对照组(普萘洛尔0.4 mg·kg^(-1)·d^(-1))、3个剂量TMP组(TMP 60,30,15 mg·kg^(-1)·d^(-1)),连续给药7 d。记录小鼠心电图,全自动生化分析仪测定血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、过氧化氢(H_2O_2)和总抗氧化能力(T-AOC)的变化;HE和TTC染色观察心肌病理损伤和梗死情况。结果 TMP能明显改善ISO诱导的心电图ST段偏移以及心肌损伤,缩小梗死面积。与模型组[CK-MB:(1562.46±138.92)U·L^(-1);LDH:(6973.28±285.50)U·L^(-1);T-AOC:(2.99±1.25)U·mL^(-1);H_2O_2:(92.52±11.42)mmol·L^(-1)]比较,TMP各组的[CK-MB:(605.81±117.72),(838.67±159.73),(1264.37±134.17)U·L^(-1));LDH:(2661.79±229.27),(5776.16±331.39),(6014.59±291.56)U·L^(-1));H_2O_2:(31.98±7.38),(67.06±18.43),(86.62±13.41)mmol·L^(-1)]的水平显著降低,而T-AOC[(7.54±2.51),(5.80±2.53),(4.93±2.21)U·mL^(-1)]水平明显升高(均P<0.05,P<0.01)。结论 TMP对小鼠急性心肌缺血具有保护作用,这可能与降低缺血小鼠心肌酶的水平及防止缺血引起的氧化应激损伤有关。

Objective To investigate the protective effects and mechanism of tetramethylpyrazine（ TMP） on isoproterenol（ ISO）- induced acute myocardial ischemia. Methods BALB / c mice were randomly divided into 6 groups： normal group（ saline 10 mg·kg^（-1）·d^（-1））,model group（ ISO 3 mg·kg^（-1）·d^（-1）,three times for three days）,control group（ propranolol 0. 4 mg · kg^（-1）· d^（-1））,different dose TMP group（ 60,30,15 mg·kg^（-1）·d^（-1））,10 mice in each group. All groups were administered drugs for 7 days. Then ISO was given intraperitoneally to establish acute myocardial ischemia model. Tetrazolium chloride（ TTC） staining was used to determine focal myocardial ischemia and hematoxylin- eosin（ HE） staining was performed in histopathological examination. MB isoenzyme of creatine kinase（ CK- MB）,lactate dehydrogenase（ LDH） levels and hydrogen peroxide（ H_2O_2）,total antioxidant capacity（ T- AOC） of serum were detected. Results TMPobviously attenuated abnormal electrocardiogram with ST- segment elevation,myocardial damage and ischemia region area in model mice. Compared with model group [CK- MB：（ 1562. 46 ± 138. 92） U · L^（-1）; LDH：（ 6973. 28 ± 285. 50） U·L^（-1）; T- AOC：（ 2. 99 ± 1. 25） U·mL^（-1）; H_2O_2：（ 92. 52 ± 11. 42） mmol·L^（-1）],TMP group significantly decreased the levels of serum [CK- MB：（ 605. 81 ± 117. 72）,（ 838. 67 ± 159. 73）,（ 1264. 37 ± 134. 17） U·L^（-1））; LDH：（ 2661. 79 ± 229. 27）,（ 5776. 16 ± 331. 39）,（ 6014. 59 ± 291. 56） U·L^（-1））;H_2O_2：（ 31. 98 ± 7. 38）,（ 67. 06 ± 18. 43）,（ 86. 62 ± 13. 41） mmol·L^（-1）]and increased T- AOC [（ 7. 54 ± 2. 51）,（ 5. 80 ± 2. 53）,（ 4. 93 ± 2. 21） U · mL^（-1）] levels of myocardial ischemia mice（ P〈0. 05 or P〈0. 01）.Conclusion TMP would alleviate Iso- induced acute myocardial ischemia,which may be associated with the decrease of cardiac enzymes and its protective effects against oxidative stress.