OBJECTIVE: To determine whether Shunxin decoction(顺心组方) improves diastolic function in rats with heart failure with preserved ejection fraction(HFp EF) by regulating the cyclic guanosine monophosphatedependent pro...OBJECTIVE: To determine whether Shunxin decoction(顺心组方) improves diastolic function in rats with heart failure with preserved ejection fraction(HFp EF) by regulating the cyclic guanosine monophosphatedependent protein kinase(c GMP-PKG) signaling pathway. METHODS: Except for control group 8 and sham surgery group 8, the remaining 32 male Sprague-Dawlay rats were developed into HFp EF rat models using the abdominal aorta constriction method. These rats in the HFp EF model were randomly divided into the model group, the Shunxin high-dose group, the Shunxin lowdose group, and the Qiliqiangxin capsule group. The three groups received high-dose Shunxin decoction, lowdose Shunxin decoction, and Qiliqiangxin capsule by gavage, respectively, for 14 d. After the intervention, the diastolic function of each rat was evaluated by testing E/A, heart index, hematoxylin-eosin staining, Masson, myocardial ultrastructure, and N-terminal pro-brain natriuretic peptide(NT-pro BNP). The Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) software was used to predict targets for which Shunxin decoction acts on the c GMP-PKG pathway. Natriuretic peptide receptor A(NPRA) and guanylate cyclase(GC) were detected by immunohistochemistry, and e NOS, phosphodiesterase 5A(PDE5A), and c GMP-dependent protein kinase 1(PKG I) were determined by Western blotting. RESULTS: Compared to the model group, the thickness of the interventricular septum at the end of diastole(IVSd) and the thickness of the posterior wall at the end of diastole(PWd) of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group were all significantly reduced(P < 0.01). Furthermore, Shunxin decoction high-dose group E/A value was decreased(P < 0.01). Compared to the model group, the expression of NPRA and GC increased in the Shunxin decoction low-dose group and the Qiliqiangxin capsule group(P < 0.01). Compared to the model group, the expressions of e NOS and PKG I increased(P < 0.05) in the Shunxin decoction high-dose group. The expression of PDE5A expression decreased in the myocardium of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group compared to the model group(P < 0.01). CONCLUSIONS: Shunxin decoction can improve diastolic function in rats with HFp EF. It increases the expression of NPRA, GC, and e NOS in the myocardial cell c GMP-PKG signaling pathway, upregulates c GMP expression, decreases PDE5A expression to reduce the c GMP degradation. Thus, the c GMP continually stimulates PKG I, reversing myocardial hypertrophy and improving myocardial compliance in HFp EF rats.展开更多
基金Supported by Lanzhou Science and Technology Planning Project:Study on a New Traditional Chinese Herb Preparation for Treating HFp EF (No. 2017-4-125)Belt and Road Special Project of Lanzhou University:Study on Countermeasures of Gansu Traditional Chinese Medicine Industry Entering Five Central Asian Countries (No. 2018ldbrzd004)。
文摘OBJECTIVE: To determine whether Shunxin decoction(顺心组方) improves diastolic function in rats with heart failure with preserved ejection fraction(HFp EF) by regulating the cyclic guanosine monophosphatedependent protein kinase(c GMP-PKG) signaling pathway. METHODS: Except for control group 8 and sham surgery group 8, the remaining 32 male Sprague-Dawlay rats were developed into HFp EF rat models using the abdominal aorta constriction method. These rats in the HFp EF model were randomly divided into the model group, the Shunxin high-dose group, the Shunxin lowdose group, and the Qiliqiangxin capsule group. The three groups received high-dose Shunxin decoction, lowdose Shunxin decoction, and Qiliqiangxin capsule by gavage, respectively, for 14 d. After the intervention, the diastolic function of each rat was evaluated by testing E/A, heart index, hematoxylin-eosin staining, Masson, myocardial ultrastructure, and N-terminal pro-brain natriuretic peptide(NT-pro BNP). The Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) software was used to predict targets for which Shunxin decoction acts on the c GMP-PKG pathway. Natriuretic peptide receptor A(NPRA) and guanylate cyclase(GC) were detected by immunohistochemistry, and e NOS, phosphodiesterase 5A(PDE5A), and c GMP-dependent protein kinase 1(PKG I) were determined by Western blotting. RESULTS: Compared to the model group, the thickness of the interventricular septum at the end of diastole(IVSd) and the thickness of the posterior wall at the end of diastole(PWd) of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group were all significantly reduced(P < 0.01). Furthermore, Shunxin decoction high-dose group E/A value was decreased(P < 0.01). Compared to the model group, the expression of NPRA and GC increased in the Shunxin decoction low-dose group and the Qiliqiangxin capsule group(P < 0.01). Compared to the model group, the expressions of e NOS and PKG I increased(P < 0.05) in the Shunxin decoction high-dose group. The expression of PDE5A expression decreased in the myocardium of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group compared to the model group(P < 0.01). CONCLUSIONS: Shunxin decoction can improve diastolic function in rats with HFp EF. It increases the expression of NPRA, GC, and e NOS in the myocardial cell c GMP-PKG signaling pathway, upregulates c GMP expression, decreases PDE5A expression to reduce the c GMP degradation. Thus, the c GMP continually stimulates PKG I, reversing myocardial hypertrophy and improving myocardial compliance in HFp EF rats.
