粉防己碱通过JAK2-STAT3途径减轻心肌缺血/再灌注损伤

目的：探讨粉防己碱减轻心肌缺血/ 再灌注（I/R）损伤的可能机制。方法：将大鼠随机分为假手术组、I/R 组、 粉防己碱组、粉防己碱+AG490 组，大鼠心肌I/R 模型采用结扎冠状动脉左前降支法制备。采用氯化三苯四氮唑 （TTC）测量心肌梗死面积，全自动生化分析仪测定冠状动脉流出物液的乳酸脱氢酶（LDH）水平，Powerlab/ 8SP 数据采集分析系统进行血液动力学监测，包括心率（HR）、左心室舒张压（LVDP）、左心室舒张末压（LVEDP） 和左心室内压最大上升速率（+dp/dtmax）。ELISA 试剂盒测定心肌三磷酸腺苷（ATP）含量，荧光法检测线粒体 活性氧（ROS）的生成率，免疫印迹检测凋亡相关蛋白Bax、Bcl-2 表达以及p-JAK2、p-STAT3 信号分子的表达。 结果：与I/R 组相比，粉防己碱组LVDP 和+dp/dtmax 显著增加，LVEDP、心肌梗死面积和LDH 释放显著降低； 与粉防己碱组相比，粉防己碱+AG490 组的LVDP 和+dp/dtmax 显著降低，LVEDP、心肌梗死面积和LDH 水平显 著增加。与 I/R 组相比，粉防己碱组心肌p-JAK2、p-STAT3 和Bcl-2 表达显著增加，而Bax 表达降低；与粉防己 碱组相比，粉防己碱+AG490 组的心肌p-JAK2、p-STAT3 和Bcl-2 表达显著降低，而Bax 表达升高。与 I/R 组相比， 粉防己碱组ATP 含量显著增加，线粒体ROS的产生率显著降低；与粉防己碱组相比，粉防己碱+AG490 组ATP 含 量显著降低，线粒体ROS的产生率显著升高。结论：粉防己碱可能通过JAK2-STAT3 通路的激活促进线粒体ROS 生成减少和线粒体ATP 含量增加，从而减轻大鼠心肌缺血/ 再灌注损伤。

Tetrandrine reduces myocardial ischemia/reperfusion injury through JAK2-STAT3 pathway

Objective To explore the possible mechanism of tetrandrine to reduce myocardial ischemia/reperfusion （I/R） injury. Methods The rat myocardial I/R model was prepared by ligating the left anterior descending coronary artery， and rats were randomly divided into sham operation group， I/R group， tetrandrine group， and tetrandrine+AG490 group. After reperfusion， triphenyltetrazole chloride （TTC） was used to detect myocardial infarction area， automatic biochemical analyzer was used to determine the lactic dehydrogenase （LDH） level of coronary effluent fluid， and Powerlab/8SP data acquisition and analysis system was used for hemodynamics scientific monitoring， including heart rate （HR）， left ventricular developed pressure （LVDP）， left ventricular end diastolic pressure （LVEDP） and maximum rate of rise and fall of left ventricular pressure （+dp/dtmax）. ELISA detection kit was used to determine the content of myocardial adenosine triphosphate （ATP）， and fluorescence method was used to detect the generation rate of mitochondrial reactive oxygen species （ROS）. Western blotting was used to detect the expression of apoptosis-related proteins Bax， Bcl-2 and p-JAK2， p-STAT3. Results Compared with the I/R group， the LVDP and +dp/dtmax in the tetrandrine group increased significantly， and the LVEDP， myocardial infarction area and LDH release were significantly reduced. Compared with the tetrandrine group， the LVDP and +dp/dtmax decreased significantly， and the level of LVEDP， myocardial infarction area and LDH release increased significantly. Compared with the I/R group， the expression of p-JAK2， p-STAT3 and Bcl-2 in the myocardium of the tetrandrine group increased significantly， while the expression of Bax decreased. Compared with the tetrandrine group， the expression of p-JAK2， p-STAT3 and Bcl-2 in the myocardium of the tetrandrine+AG490 group was significantly reduced， while the expression of Bax was increased. Compared with the I/R group， the ATP content of the tetrandrine group was significantly increased， and the generation rate of mitochondrial ROS was significantly reduced. Compared with the tetrandrine group， theATP content of the tetrandrine+AG490 group was significantly reduced， and the generation rate of mitochondrial ROS was significantly increased. Conclusion Tetrandrine may reduce mitochondrial ROS production and increase mitochondrial ATP content through the activation of JAK2-STAT3， thereby reducing myocardial ischemia/reperfusion injury in rats.