Study on endoplasmic reticulum stress mechanism of treating heart failure with Yiqi Huoxue Recipe
ZHANG Ting1 WANG Jie2 WU Aiming1 MA Zhe1 ZHAO Yizhou1 ZHANG Dongmei1 JIN Qiushuo1 LOU Lixia1
1.Chinese Internal Medicine Laboratory of of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China; 2.Department of Cardiology, the First People′s Hospital of Lanzhou New District, Gansu Province, Lanzhou 730300, China
Abstract：Objective To explore the molecular mechanism of improvement effect of Yiqi Huoxue Recipe in heart failure treatment by regulating endoplasmic reticulum stress signaling (ERS) pathway. Methods Thirty SPF male SD rats were divided into sham operation group (10 rats) by the random number table method, and the remaining 20 rats model of acute myocardial infarction was prepared by ligating the anterior descending branch of the left coronary artery. Rats with successful modeling were randomly divided into model group and Yiqi Huoxue group, with 10 rats in each group. The rats in model group and sham operation group were gavaged with deionized water 5 mL/(kg·d), 1 time/d. Rats in Yiqi Huoxue group were gavaged with Yiqi Huoxue Recipe 5 mL/(kg·d). The drug was administered continuously for 4 weeks. Hemodynamic index including left ventricular end-diastolic pressure (LVEDP), left ventricular internal pressure maximal rate of increase (+dp/dt max), left heart maximum drop rate of indoor pressure (-dp/dt max), left ventricular systolic pressure (LVSP) and heart rate (HR) were detected by left ventricular intubation method. The expressions of brain natriuretic peptide (BNP) and calcineurin A (CaNA) mRNA were detected by Rt-PCR and the protein levels of caspase-12, protein kinase R-like endoplasmic reticulum kinase (PERK), inositol requiring enzymes 1(IRE1) and glucose-regulated protein 78 (GRP78) were detected by Western blot. Results LVEDP, -dp/dt max and HR in model group were higher than those in sham group, +dp/dt max and LVSP were significantly lower than those in sham operation group, and the differences were highly statistically significant (P < 0.01). LVEDP, -dp/dt max and HR of rats in Yiqi Huoxue group were lower than those in model group, LVSP and +dp/dt max were higher than those in model group, and the differences were highly statistically significant (P < 0.01). The expressions of BNP and CaNA mRNA in model group were higher than those in sham operation group, with statistically significant differences (P < 0.05 or P < 0.01). The expressions of BNP and CaNA mRNA in Yiqi Huoxue group were lower than those in model group, with statistically significant differences (P < 0.05). The expression levels of caspase-12, PERK, IRE1 and GRP78 in model group were higher than those in sham operation group, with statistically significant differences (P < 0.05). The expression levels of caspase-12, PERK and IRE1 in Yiqi Huoxue group were lower than those in model group, with statistically significant differences (P < 0.05). Conclusion Yiqi Huoxue Recipe can improve the cardiac function of rats with heart failure induced by myocardial infarction, and the mechanism included may be related to the endoplasmic reticulum stress signaling pathway regulation.
2020, Vol. 17 
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