益心方调控SIRT1/Nrf2/HO-1信号通路改善大鼠心肌缺血再灌注后损伤

作者	单位
董莉;杨燕玲;郑钰凡;戎靖枫	1.上海中医药大学附属曙光医院心血管内科（上海 201203）,2.上海中医药大学附属曙光医院心血管研究所（上海 201203）

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中文摘要:

目的探讨中药复方益心方改善心肌缺血再灌注后损伤的作用及其机制。方法将75只清洁级大鼠分为5组：假手术组（Sham），缺血再灌注组（IR），益心方+缺血再灌注组（YXF+IR），益心方+缺血再灌注+ SIRT1抑制剂组（YXF+IR+EX527），益心方+缺血再灌注+ SIRT1激动剂组（YXF+IR+SRT1720），每组各15只。再灌注7 d后超声心动图检测心功能；免疫荧光法检测心肌细胞凋亡率和组织活性氧（ROS）的活性；ELISA检测血清中的心肌酶水平；Western Blot检测相关蛋白表达。结果与Sham组比较，IR组大鼠的左室射血分数（LVEF）、左室短轴缩短率（LVFS）降低，心肌凋亡指数和ROS活性升高，血清中肌酸激酶（CK）、乳酸脱氢酶（LDH）、丙二醛（MDA）、过氧化氢（H2O2）、琥珀酸脱氢酶（SDH）水平升高，超氧化物歧化酶（SOD）水平降低，沉默信息调节因子1（SIRT1）、核因子E2相关因子2（Nrf2）、血红素氧合酶1（HO-1）、B淋巴细胞瘤-2（Bcl-2）蛋白表达下降，B淋巴细胞瘤-2相关蛋白X（Bax）、胱天蛋白酶3（Caspase 3）表达增加，差异均有统计学意义（P＜0.01，P＜0.05）。与IR组比较，YXF+IR和YXF+IR+SRT1720组LVEF、LVFS升高，心肌凋亡指数和ROS活性降低，血清中CK、LDH、MDA、H2O2、SDH水平降低，SOD水平升高，SIRT1、Nrf2、HO-1 BCL-2蛋白表达升高，Bax、Caspase 3蛋白表达降低，差异均有统计学意义（P＜0.01，P＜0.05）。与YXF+IR组比较，YXF+IR+EX527组CK、LDH、MDA、H2O2、SDH升高，SOD 水平下降，SIRT1、Nrf2、HO-1、Bcl-2 表达降低，Bax、Caspase 3 表达升高，差异均有统计学意义（P＜0.01，P＜0.05）。结论益心方可以通过上调SIRT1/ Nrf2/HO-1信号通路改善心肌缺血再灌注损伤大鼠心功能，减轻心肌缺血再灌注后氧化应激损伤。

英文摘要:

Objective To explore the role and its mechanism of Yixin Formula（YXF）on myocardial ischemia-reperfusion injury （MIRI） in rats. Methods Totally 75 Wistar rats were divided into five groups randomly：Sham，IR，YXF+IR，YXF + IR + SIRT1-inhibitor （EX527），and YXF+IR+SIRT1-agonist （SRT1720）groups， 15 in each group. Cardiac function was measured by echocardiography，immunofluorescence was performed to detect apoptosis and reactive oxygen species（ROS） level in heart tissues after 7 days of reperfusion. The level of serum myocardial enzymes was detected by ELISA. Subsequently，the expression of related proteins was detected by Western Blot. Results Compared with the Sham group，the left ventricular ejection fraction（LVEF） and left ventricular fractional shortening（LVFS） of the rats in the IR group were decreased，the apoptosis rate，ROS，creatine kinase（CK），lactate dehydrogenase（LDH），malondialdehyde（MDA），hydrogen peroxide（H2O2），and succinate dehydrogenase（SDH）were significantly increased in the IR group，while superoxide dismutase（SOD） level was decreased. The protein expression of silent information regulatory factor 1（SIRT1），nuclearfactor erythroidderived 2-like 2（Nrf2），heme oxygenase-1（HO-1），and B-cell lymphoma-2（Bcl-2） were decreased，while Bcl2-associated X（Bax） and cysteinyl aspartate specific proteinase 3（Caspase 3）were increased in the IR group，the differences were statistically significant（P<0.01，P<0.05）. Compared with IR group，LVEF and LVFS increased，apoptotic index and ROS decreased，the level of CK，LDH，MDA，H2O2 and SDH decreased，and the SOD level increased，the protein expression of SIRT1，Nrf2，HO-1 and Bcl-2 was increased，while Bax and Caspase 3 were decreased in YXF+IR and YXF+IR+SRT1720 groups，the differences were statistically significant（P<0.01，P<0.05）. Compared with YXF+IR group，CK，LDH，MDA，H2O2 and SDH levels increased，while SOD level decreased，the protein expressions of SIRT1，Nrf2，HO-1 and Bcl-2 decreased，while Bax and Caspase 3 expression increased in YXF+IR+EX527 group，the differences were statistically significant（P<0.01，P<0.05）. Conclusion YXF can improve cardiac function and reduce oxidative stress injury after myocardial ischemia/reperfusion in MIRI rats by upregulating SIRT1/ Nrf2/HO-1 signaling pathway.

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