Mechanism of Wenxin Granule Inhibits Myocardial Cell Apoptosis After Myocardial Infarctionby Regulating Endoplasmic Reticulum Stress in Rats / 中国实验方剂学杂志

ABSTRACT

Objective:To explore the intervention effect of Wenxin granule on endoplasmic reticulum stress apoptosis pathway and its related mechanism in rats with myocardial infarction. Method:Ligating the left anterior descending coronary artery to establish the rat model， the rats were randomly divided into 5 groups， namely sham group， model group， betaloc group and low， high-dose Wenxin granule groups，10 in each group. The sham group and the model group were given 10 mL∙kg^-1∙d^-1 deionized water， the low， high-dose modified Wenxin groups were given 1.35， 2.7 g∙kg^-1∙d^-1 aqueous solution respectively， and the betaloc group was given 2.25 mg∙kg^-1∙d^-1 aqueous solution. After 14 days，the catheter method was used to detect the cardiac hemodynamics and hematoxylin-eosin staining （HE） was used to observe the pathological morphological changes. The levels of endoplasmic reticulum stress protein glucose regulatory protein 78（GRP78）， protein kinase R like endoplasmic reticulum kinase（PERK）， phosphorylated activated PERK（p-PERK）， activated transcription factor 6 （ATF6）， nuclear transcription factor X cassette binding protein（XBP1） and apoptosis protein C/EBP homologous protein（CHOP）， B cell lymphoma/leukemia-2（Bcl-2） and Bcl-2 associated X protein（Bax） were detected by Western blot. Deoxyribonucleotide end-transferase-mediated notch end labeling （TUNEL） was also used to detect the myocardial cell apoptosis. Result:Compared with control group， the levels of the maximum ascending rate of left ventricular pressure（+dp/dt_max）， the maximum descending rate of left ventricular pressure（-dp/dt_max） and the left ventricular systolic blood pressure（LVSP） were decreased significantly（<italic>P</italic><0.05），but the level of the left ventricular end diastolic blood pressure （LVEDP） was significantly increased（<italic>P</italic><0.05）. The expressions of GRP78， p-PERK， PERK， ATF6， XBP1， CHOP， Bax and apoptosis index were increased significantly （<italic>P</italic><0.05，<italic>P</italic><0.01）， while Bcl-2/Bax and Bcl-2 were decreased significantly（<italic>P</italic><0.01） in model group. Compared with the model group， the levels of -dp/dt_max and Bcl-2 were increased significantly （<italic>P</italic><0.05），while the level of the apoptosis index was decreased significantly（<italic>P</italic><0.01） in low-dose Wenxin granule group. In high-dose Wenxin granule group， the levels of +dp/dt_max and -dp/dt_max were increased significantly（<italic>P</italic><0.05，<italic>P</italic><0.01）， the levels of endoplasmic reticulum stress pathway protein GRP78， p-PERK， PERK， ATF6， XBP1，apoptosis-related protein CHOP， Bax and apoptosis index were decreased significantly（<italic>P</italic><0.01）， but Bcl-2 and Bcl-2/Bax were increased significantly （<italic>P</italic><0.01）. Conclusion:Wenxin granule has effect in inhibiting excessive endoplasmic reticulum stress， reducing myocardial cell apoptosis and improving cardiac hemodynamics. Its molecular mechanism may be related to decrease the levels of GRP78， PERK， p-PERK， ATF6， XBP1， CHOP， Bax and increasing the expression of Bcl-2.