基于JAK2/STAT3信号通路观察右美托咪定减轻大鼠心肌缺血再灌注损伤和抑制凋亡作用机制

doi:10.13418/j.issn.1001-165x.2022.1.11

摘要/Abstract

摘要： 目的探讨右美托咪定在大鼠心肌缺血再灌注损伤（myocardial ischemia-reperfusion injury，MIRI）中的抗凋亡作用，以及其对蛋白酪氨酸激酶2/信号转导和转录激活因子3（janus kinase 2/signaltransducer and activator of transcription 3，JAK2/STAT3）信号的调节机制。方法将大鼠随机分为假手术组，模型组，实验组及对照组，结扎左冠状动脉前降支构建缺血再灌注大鼠模型，假手术组只穿线不结扎，实验组、对照组大鼠术前1 h分别腹腔注射5.0 μg/kg的右美托咪定、JAK2/STAT3信号通路激动剂SC-39100，假手术组、模型组大鼠注射等剂量的生理盐水。心彩超仪检查各组大鼠的左室收缩压(1eft ventricular systohc pressure，LVSP）、左室舒张末压（1eft ventricular end-diastolic pressure，LVEDP）、左室压力上升最大速率（1eft ventricular pressure rise，+dp/dtmax）及左室压力下降最大速率（1eft ventricular pressure drop，-dp/dtmax）。TUNEL染色检测各组大鼠心肌细胞凋亡。DCFH-DA检测各组大鼠心肌组织中ROS水平。Western blot检测各组大鼠心肌组织中p-JAK2，p-STAT3的表达水平。结果与假手术组相比，模型组大鼠的LVSP、+dp/dtmax、-dp/dtmax明显降低，LVEDP、心肌凋亡率、ROS荧光强度、p-JAK2，p-STAT3表达明显升高，差异均具有统计学意义（P<0.05）；与模型组相比，实验组、对照组大鼠的LVSP、+dp/dtmax、-dp/dtmax、p-JAK2，p-STAT3表达明显升高，LVEDP、心肌凋亡率、ROS荧光强度、明显降低，差异均具有统计学意义（P<0.05）。结论右美托咪定预处理能降低大鼠心肌缺血再灌注损伤，降低心肌细胞凋亡，这可能与激活JAK2/STAT3信号，抑制氧化应激有关。

关键词: 右美托咪定； , , 心肌缺血再灌注损伤； , , 细胞凋亡； , , 蛋白酪氨酸激酶2/信号转导和转录激活因子3信号通路

Abstract: Objective To explore the mechanism of dexmedetomidine reducing myocardial ischemia-reperfusion injury and inhibiting apoptosis and its regulation signaling of janus kinase 2/signaltransducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Methods Rat were randomly divided into the following 4 groups: a sham operation group, a model group, an experimental group, and a control group. The anterior descending branch of the left tubular artery was ligated to construct an ischemia-reperfusion rat model. The sham operation group only threaded without ligation. The rats in the experimental group and in the control group were intraperitoneally injected with 5.0 μg/kg dexmedetomidine and JAK2/STAT3 signaling pathway agonist SC-39100 1 h before surgery, and the rats in the sham group and model group were injected with equal doses of normal saline. Cardiac ultrasonography was used to examine the left ventricular systohc pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and left ventricular pressure rise rate (1eft ventricular pressure rise, +dp/dtmax) and the maximum rate of left ventricular pressure drop (1eft ventricular pressure drop, -dp/dtmax). TUNEL staining was used to detect the apoptosis of myocardial cells. DCFH-DA staining was used to detect the level of ROS in the myocardium. Western blot was used to detect the expression levels of p-JAK2 and p-STAT3 in rat myocardium. Results Compared with the sham group, the LVSP, +dp/dtmax, -dp/dtmax of the model group significantly reduced, and the LVEDP, the myocardial apoptosis rate, the fluorescence intensity of ROS, the expression of p-JAK2, and p-STAT3 significantly increased, with statistical differences (P<0.05). Compared with the model group, the LVSP, +dp/dtmax, -dp/dtmax, the expression of p-JAK2, p-STAT3 in the experimental group and the control group obvious increased, the LVEDP, the myocardial apoptosis rate, the fluorescence intensity of ROS significantly decreased, with statistical differences (P<0.05). Conclusions Pretreatment with dexmedetomidine can significantly reduce myocardial ischemia-reperfusion injury and reduce cardiomyocyte apoptosis, which may be related to the activation of JAK2 / STAT3 signal and inhibition of oxidative stress.

Key words: Dexmedetomidine; , , Myocardial ischemia-reperfusion injury; , , Cell apoptosis, Janus kinase 2/signaltransducer and activator of transcription 3 signaling pathway

中图分类号:

R542.2

吴亚辉, 王韬甫, 林洪启. 基于JAK2/STAT3信号通路观察右美托咪定减轻大鼠心肌缺血再灌注损伤和抑制凋亡作用机制[J]. 中国临床解剖学杂志, 2022, 40(1): 55-61.

Wu Yahui, Wang Taofu, Lin Hongqi. The mechanism of dexmedetomidine reducing myocardial ischemia-reperfusion injury and inhibiting apoptosis based on JAK2 / STAT3 signaling pathway[J]. Chinese Journal of Clinical Anatomy, 2022, 40(1): 55-61.

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