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基于FXR/SHP通路探讨电针预处理对心肌缺血再灌注损伤大鼠心肌细胞凋亡的影响

[Effect of electroacupuncture preconditioning on myocyte apoptosis in myocardial ischemia-reperfusion injury rats based on FXR/SHP pathway].

作者信息

Liu Zhen-Zhen, Huang Wei, Xiang Li-Li, Yang Qi-Qi, Xue Yi-Xuan, Wu Song, Li Jia

机构信息

College of Acupuncture-moxibustion and Orthopedics, Hubei University of Chinese Medicine /Hubei Provincial Collaborative Innovation Center of Preventive Treatment of Diseases with Acupuncture and Moxibustion, Wuhan 430061, China.

First Clinical College, Hubei University of Chinese Medicine, Wuhan 430061; Department of Acupuncture-moxibustion, Hubei Provincial Hospital of Taditional Chinese Medicine, Wuhan 430061.

出版信息

Zhen Ci Yan Jiu. 2021 May 25;46(5):368-74. doi: 10.13702/j.1000-0607.200617.

Abstract

OBJECTIVE

To observe the effect of electroacupuncture (EA) preconditioning on left-cardiac function, contents of serum TNF-α and IL-6 and expression of myocardial farnesoid X receptor(FXR), small heterodimer partner (SHP), apoptosis inducing factor (AIF) and heat shock proteins 70 (HSP70) genes in myocardial ischemia-reperfusion injury (MIRI) rats, so as to explore its mechanisms underlying improvement of ischemic myocardial injury.

METHODS

Forty male Wistar rats were randomly divided into normal control, sham operation, MIRI model and EA pretreatment groups, with 10 rats in each group. Rats of the sham operation group received exposure of the thorax and heart. The MIRI model was established by occlusion of the anterior descending branch of the left coronary artery (LAD). EA (2 Hz/100 Hz and 1 mA) was applied to bilateral "Neiguan" (PC6), "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, once a day for 7 days. The left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP)and maximal rates of rise and fall of left ventricular pressure (±dp/dt) were detected, the contents of serum TNF-α and IL-6 were detected by using enzyme-linked immunosorbent assay (ELISA), and the expression of FXR, SHP, AIF and HSP70 apoptotic genes in the myocardial tissue were measured by fluorescent quantitative RT-PCR.

RESULTS

Compared with the normal control group, the LVEDP, contents of serum TNF-α and IL-6, and the expression levels of myocardial FXR, SHP, AIF and HSP70 mRNAs were significantly increased (<0.05), while LVSP and ±dp/dt levels were obviously decreased in the model group (<0.05). In comparison with the model group, MIRI-induced increases of LVEDP, TNF-α and IL-6 contents, and FXR, SHP and AIF mRNA expression and decreases of ±dp/dtmax and LVSP levels were reversed(<0.05), except HSP70 mRNA expression with significantly increased (<0.05) in the EA pretreatment group.

CONCLUSION

EA pretreatment can protect the left ventricular function of the ischemic heart in MIRI rats, which may be related to its effects in reliving peripheral inflammation and regulating the expression levels of apoptosis-related factors FXR, SHP, AIF and HSP70 in the myocardium.

摘要

目的

观察电针预处理对心肌缺血再灌注损伤(MIRI)大鼠左心功能、血清肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)含量及心肌法尼酯X受体(FXR)、小异二聚体伴侣(SHP)、凋亡诱导因子(AIF)和热休克蛋白70(HSP70)基因表达的影响,以探讨其改善缺血性心肌损伤的机制。

方法

将40只雄性Wistar大鼠随机分为正常对照组、假手术组、MIRI模型组和电针预处理组,每组10只。假手术组大鼠仅打开胸腔暴露心脏。采用结扎左冠状动脉前降支(LAD)的方法建立MIRI模型。电针(2 Hz/100 Hz,1 mA)刺激双侧“内关”(PC6)、“足三里”(ST36)和“关元”(CV4),每次20分钟,每天1次,共7天。检测左心室舒张末压(LVEDP)、左心室收缩压(LVSP)及左心室压力最大上升和下降速率(±dp/dt);采用酶联免疫吸附测定(ELISA)法检测血清TNF-α和IL-6含量;采用荧光定量逆转录聚合酶链反应(RT-PCR)检测心肌组织中FXR、SHP、AIF和HSP70凋亡基因的表达。

结果

与正常对照组比较,模型组LVEDP、血清TNF-α和IL-6含量及心肌FXR、SHP、AIF和HSP70 mRNA表达水平均显著升高(<0.05),而LVSP及±dp/dt水平明显降低(<0.05)。与模型组比较,电针预处理组可逆转MIRI所致的LVEDP、TNF-α和IL-6含量升高,FXR、SHP和AIF mRNA表达增加及±dp/dtmax和LVSP水平降低(<0.05),但电针预处理组HSP70 mRNA表达显著增加(<0.05)。

结论

电针预处理可保护MIRI大鼠缺血心脏的左心室功能,其机制可能与减轻外周炎症反应及调节心肌凋亡相关因子FXR、SHP、AIF和HSP70的表达水平有关。

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