| Objective:To observe the effects of Qiangxin capsule on Chronic Heart Failure(CHF), illustrate the mechanism of Qiangxin capsule on endoplasmic reticulum stress PERK-eIF2a pathway in rats. And then provide the experimental basis for the clinical application of Qiangxin capsule and enrich Wenyang Huayin supplementing qi and activating blood circulation method in the CHF treatment theoryMethods:100 Male SD rats were randomly divided into two groups. The control group was 10 and the model group was 90.The model group was intravenous injected by Adriamycin solution to establish the rats model of CHF and the control group was intravenous injected by 0.9% Nacl. After 6 weeks, the animal model of CHF was successfully established.65 CHF model rats were randomly divided into five groups which were signed by model group, western medicine group, low dose group, middle dose group, high dose group. Totally, we got six groups after animals grouping. The low dose group, middle dose group and high dose group rats were gavaged by the different dose of 0.66g/kg·d,1.32g/kg·d,2.64g/kg·d. The western medicine group was gavaged by Enalapril solution with 1.8mg/kg·d, the model group and the control group were gavaged by 0.9% Nacl. Each group was gavaged 1 times a day and the treatment period was 4 weeks. After the treatment, we observed the general state of each groups and measured the heart weight index. The cardiac function of rats was evaluated by echocardiography. The pathological changes of myocardial tissues was observed by HE staining. The serum NT-proBNP level was detected by ELISA. The myocardial apoptosis was detected by TUNEL.The expression of GRP78 protein was detected by Immunohisto chemical method.The expression of PERK, p-PERK, eIF2a,p-eIF2a,ATF4 protein was detected by Western blot. We want to clearify the mechanism of Qiangxin capsule on CHF rats in the endoplasmic reticulum stress PERK-eIF2a signaling way.Result:1.The general state of rats:The Qiangxin capsule could improve the general state of CHF rats.2.The echocardiography diagram in the CHF rats:Compared with the control group, The LVEDD and LVESD of model group were significantly increased(P<0.01),and the LVEF and LVFS were significantly decreased(P<0.01).Compared with the model group, the LVEDD and LVESD in each treatment group was significantly decreased(P<0.01), Meanwhile the LVEF and LVFS were significantly increased(P<0.01).Compared with the western medicine group, the LVEDD and LVESD of the low dose group were significantly increased(P<0.01) and the LVEF and LVFS were decreased (P<0.05,P<0.01),the LVEDD and LVESD of middle dose group and high dose group were increased no statistical significance(P>0.05),the LVEF and LVFS were decreased no statistical significance(P>0.05).The LVEF and LVFS of high dose group was higher than the low dose group(P<0.05).3.The serum NT-proBNP levels in the CHF rats:Compared with the control group, the NT-proBNP level in model group was significantly increased(P<0.01). Compared with the model group, the NT-proBNP level in treatment group was significantly decreased (P<0.01). Compared with the western medicine group, The NT-proBNP level in low dose group and the middle dose was increased (P<0.05,P<0.01),high dose group were increased no statistical significance(P>0.05).The NT-proBNP of high dose group was lower than the low dose group(P<0.05).4.Heart weight index:Compared with the control group, the model group HWI was significantly increased(P<0.01). Compared with the model group, the HWI in each treatment group was significantly decreased(P<0.01).Compared with the western medicine group,the HWI in low dose group was significantly decreased(P<0.01),middle dose group and high dose group were increased no statistical significance(P>0.05).The HWI of high dose group was lower than the low dose group(P<0.05).5.Morphological changes of the rat:Qiangxin capsule could significantly reverse the expansion of heart, reduce myocardial cell edema, rearrange muscle fibers, decrease inflamed cells and improve other abnormal changes of myocardial pathological structure.6.Myocardial apoptosis index in rats:Compared with the control group, the apoptosis index of the model group was significantly increased (P<0.01). Compared with the model group, the apoptosis index of myocardial cells in each treatment group was decreased, the western medicine group and middle dose group were significantly decreased(P<0.01). Compared with the western medicine group, the apoptosis index in the low dose group and middle dose group were significantly increased(P<0.01),high dose group were increased no statistical significance(P>0.05).The apoptosis index of high dose group was lower than the low dose group(P<0.05).7.The expression of GRP78 protein in myocardium:Compared with the control group, the expression of GRP78 protein was significantly increased (P<0.01). Compared with the model group, the expression of GRP78 in each treatment group was significantly decreased (P<0.01). Compared with the western medicine group, the low dose group was increased(P<0.05),high dose group were increased no statistical significance(P>0.05).The GRP78 of high dose group was lower than the low dose group(P<0.01).8.The expression levels of PERK, p-PERK, eIF2α, p-eIF2α, ATF4 protein in cardiac tissue:Compared with the control group, the expression of pERK, p-PERK, eIF2α, p-eIF2α,and ATF4 in model group were significantly increased (P<0.01). Compared with the model group, the expression of PERK, p-PERK, eIF2α, p-eIF2α and ATF4 in each treatment group were decreased differently (P<0.05, P<0.01). Compared with the western medicine group, the low dose group was increased (P<0.05),middle dose group and high dose group were increased no statistical significance(P>0.05)..The PERK、 p-PERK、p-eIF2α、ATF4 of high dose group was lower than the low dose group(P<0.05).Conclusion:1.Qiangxin capsule could improve the general state of CHF rats, reduce the heart index, improve the morphology of cardiac pathology.2.Qiangxin capsule could improve the index of echocardiography in CHF rats, reduce LVEDD and LVESD, increase LVEF and LVFS, improve the heart function of CHF rats.3.Qiangxin capsule could reduce the serum level of NT-proBNP in CHF rats.4.Qiangxin capsule could reduce the cardiac muscle cell apoptosis index in CHF rats.5.Qiangxin capsule could reduce the GRP78 protein expression and inhibit the related protein expression of PERK-eIF2α pathway. It also could reduce the accumulation of misfolded proteins, decrease the apoptosis of myocardial cells and delay ventricular remodeling. |
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