川芎嗪预处理对大鼠无创肢体缺血预适应心肌保护作用的影响

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (12): 1353-1358.

川芎嗪预处理对大鼠无创肢体缺血预适应心肌保护作用的影响

张泽宇¹, 刘丹², 万青², 罗勇², 廖章萍², 汤蕾², 何明^1,2

¹南昌大学第一附属医院江西省高血压病研究所,南昌 330006,江西;
²南昌大学药学院江西省基础药理学重点实验室,南昌 330006,江西

收稿日期:2013-08-14 修回日期:2013-11-25 出版日期:2013-12-26 发布日期:2014-01-04
通讯作者: 何明,男,博士,教授,博导,研究方向:心肌急性损伤与保护。Tel: 0791-86361839 E-mail: jxhm56@163.com
作者简介:张泽宇,男,硕士研究生,研究方向:心肌急性损伤与保护。Tel: 0791-86362231 E-mail: 843052988@qq.com
基金资助:
国家自然科学基金资助(81072632)

Protective effect of tetramethylpyrazine preconditioning on rat myocardium with non-invasive limb ischemia preconditioning

ZHANG Ze-yu¹, LIU Dan², WANG Qing², LUO Yong², LIAO Zhang-ping², TANG Lei², HE Ming^1,2

¹Jiangxi Provincial Institute of Hypertension, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China;
²Jiangxi Provincial Key Laboratory of Basic Pharmacology, Nanchang University School of Pharmaceutical Science, Nanchang 330006, Jiangxi ,China

Received:2013-08-14 Revised:2013-11-25 Online:2013-12-26 Published:2014-01-04

摘要/Abstract

摘要： 目的: 探讨川芎嗪(TMP)预处理对大鼠无创肢体缺血预适应(R-IPC)心肌保护作用的影响。方法: 取成年雄性SD大鼠40只,随机均分为5组,分别为对照(Cont)组、缺血/再灌注(I/R)组、R-IPC组、TMP组、R-IPC+TMP组。预处理时R-IPC组和R-IPC+TMP组每天R-IPC预处理1次,连续 3 d;TMP组和R-IPC+TMP组每天i.p. TMP 10 mg/kg 预处理1次,连续 3 d;末次预处理 24 h 后,制备Langendorff逆灌离体心脏并作I/R损伤模型;检测冠脉流出液中乳酸脱氢酶(LDH)、肌酸磷酸激酶(CPK)活性,心肌梗死面积,心肌组织丙二醛(MDA)含量,超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、caspase-3活性,细胞凋亡情况。结果: R-IPC或TMP预处理24 h后,大鼠心脏可有效对抗急性I/R损伤性的冠脉流出液中LDH、CPK活性以及梗死面积的增加,心肌组织中MDA含量上升和SOD、GSH-Px活性降低以及caspase-3活性和凋亡指数增加(P<0.01),表现出延迟保护作用;R-IPC与TMP共同预处理 24 h 后,诱发的延迟保护作用--在LDH、CPK活性与梗死面积等指标上,二者间表现为相互协同作用稍逊于SOD、GSH-Px、caspase-3活性和凋亡指数等指标。结论: TMP预处理可有效增强R-IPC对大鼠心脏急性I/R损伤之延迟保护作用。

关键词: 川芎嗪, 缺血预适应, 缺血/再灌注损伤, 大鼠

Abstract: AIM: To explore the effect of tetramethylpyrazine(TMP) preconditioning on rat myocardium with remote ischemic preconditioning(R-IPC).METHODS: Forty adult male SD rats were randomly divided into five groups: Control(Cont) group, ischemia reperfusion(I/R) group, R-IPC group, TMP group, R-IPC+TMP group. R-IPC and R-IPC+TMP groups were pretreated with R-IPC once a day for three days; TMP and R-IPC+TMP groups were pretreated with 10 mg/kg TMP by intraperitoneal injection once a day for three days. After 24 h of last treatment, the isolated rat hearts were langendorff-perfused and I/R injury model were built. The activities of LDH and CPK in the flow, infarct size, the content of MDA, the activities of SOD, GSH-Px and caspase-3, and apoptosis were assayed.RESULTS: After 24 h of pretreatment with R-IPC or TMP, the increases of activities of LDH and CPK, infarct size, the MDA content and apoptotic index induced by acute I/R injury were reduced, decreases of activities of SOD and GSH-Px were enhanced(P<0.01). These results showed that pretreatment with R-IPC and TMP had delay protective effect. 24 h After pretreatment with R-IPC and TMP, delay protective effect was induced as follows: the results such as the activities of LDH and CPK and infarct size showed up weaker delay proterctive effect compared with the activities of SOD, GSH-Px, caspase-3 and apoptotic index.CONCLUSION: Pretreatment with TMP could effectively enhance the R-IPC on cardiac delay protection against acute I/R injury in rat.

Key words: Tetramethylpyrazine, Ischemia preconditioning, Ischemia/reperfusion injury, Rat

中图分类号:

R965.2

张泽宇, 刘丹, 万青, 罗勇, 廖章萍, 汤蕾, 何明. 川芎嗪预处理对大鼠无创肢体缺血预适应心肌保护作用的影响[J]. 中国临床药理学与治疗学, 2013, 18(12): 1353-1358.

ZHANG Ze-yu, LIU Dan, WANG Qing, LUO Yong, LIAO Zhang-ping, TANG Lei, HE Ming. Protective effect of tetramethylpyrazine preconditioning on rat myocardium with non-invasive limb ischemia preconditioning[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(12): 1353-1358.

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