参乌冠心颗粒通过调控NR3C1/GRP78抑制心肌细胞内质网应激缓解冠心病心绞痛机制研究OA

Objective To study the mechanism of Shenwu Guanxin Granules(参乌冠心颗粒)in relieving angina pectoris of coronary heart disease by regulating NR3C1/GRP78 and inhibiting endoplasmic reticulum stress of cardiomyocytes.Methods 60 healthy male SD rats were divided into 6 groups:normal group,model group,low-dose Shenwu Guanxin Granules group,medium-dose Shenwu Guanxin Granules group,high-dose Shenwu Guanxin Granules group,Compound Danshen Dropping Pills(复方丹参滴丸)group.The rats in each group were given peritoneal anesthesia with pentobarbital sodium,and the model group was injected with pituitrin 6 U/kg(concentration 2 U/mL)to establish the angina pectoris model of coronary heart disease.The normal group was injected with the same amount of normal saline.Echocardiography was used to detect the cardiac function of the rats,and myocardial histopathology was performed in all the rats.The activity of Caspase-12 in myocardium of rats in each group was detected.The mRNA and protein expression levels of NR3C1,GRP78,CHOP and ATF6 in myocardium of rats were detected by RT-PCR and Western blot,respectively.Results Comparison of LVEF among groups:Compared with normal group,model group,low-dose,medium-dose and high-dose Shenwu Guanxin Granules groups,Compound Danshen Dropping Pills group,all showed significant decreases(all P<0.05);Compared with model group,low-dose,medium-dose and high-dose Shenwu Guanxin Granules groups,Compound Danshen Dropping Pills group,all showed significant increases(all P<0.05),among low-dose,medium-dose and high-dose Shenwu Guanxin Granules groups,showed an increasing trend as the dosage of Shenwu Guanxin Granules increased;Compared with low-dose,medium-dose and high-dose Shenwu Guanxin Granules groups,Compound Danshen Dropping Pills group,all showed significant increases(all P<0.05);Compared with medium-dose and high-dose Shenwu Guanxin Granules groups,Compound Danshen Dropping Pills group,all showed significant decreases(all P<0.05);The treatment effect of high-dose Shenwu Guanxin Granules group was comparable to that of Compound Danshen Dropping Pills group.HE staining results showed that:in normal group,the myocardial tissue of rats was arranged neatly and stained uniformly,without inflammatory infiltration;in model group,the myocardial cells were hypertrophic,the cytoplasm staining was uneven,the cell gap was widened,and the inflammatory infiltration was obvious;low-dose,medium-dose and high-dose Shenwu Guanxin Granules groups,Compound Danshen Dropping Pills group had less inflammatory injury than the model group,among which the inflammatory injury degree of medium-dose Shenwu Guanxin Granules group was less than that of low-dose Shenwu Guanxin Granules group;the inflammatory injury degree of high-dose Shenwu Guanxin Granules group was less than that of medium-dose Shenwu Guanxin Granules group;the injury degree of Compound Danshen Dropping Pills group was similar to that of high-dose Shenwu Guanxin Granules group.Comparison of LVEDD,LVESD,Caspase-12 activity,mRNA and protein expression levels of NR3C1,GRP78,CHOP,and ATF6 among groups:Compared with normal group,model group,low-dose,medium-dose and high-dose Shenwu Guanxin Granules groups,Compound Danshen Dropping Pills group,all showed significant increases(all P<0.05);Compared with model group,low-dose,medium-dose and high-dose Shenwu Guanxin Granules groups,Compound Danshen Dropping Pills group,all showed significant decreases(all P<0.05),among which low-dose,medium-dose and high-dose Shenwu Guanxin Granules groups,showed a decreasing trend as the dosage of Shenwu Guanxin Granules increased;Compared with low-dose,medium-dose and high-dose Shenwu Guanxin Granules groups,Compound Danshen Dropping Pills group,all showed significant decreases(all P<0.05);Compared with medium-dose and high-dose Shenwu Guanxin Granules groups,Compound Danshen Dropping Pills group,all showed significant decreases(all P<0.05);The above indicators of high-dose Shenwu Guanxin Granules group,Compound Danshen Dropping Pills group were comparable.Conclusion Shenwu Guanxin Granules may regulate the expression of NR3C1 and GRP78,inhibit the transcription of CHOP and ATF6 and the activity of Caspase-12,thereby inhibiting endoplasmic reticulum stress in myocardial cells,reducing myocardial cell injury,and thus alleviating angina pectoris of coronary heart disease.