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

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

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3d;TMP组和R-IPC+TMP组每天i.p.TMP 10mg/kg预处理1次,连续3d;末次预处理24h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24h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24h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。

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 activ- ities 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 proteretive effect compared with the aetivities 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.