PMID- 36083484 OWN - NLM STAT- MEDLINE DCOM- 20220913 LR - 20231031 IS - 2589-451X (Electronic) IS - 0255-2922 (Print) IS - 0255-2922 (Linking) VI - 42 IP - 5 DP - 2022 Oct TI - Shunxin decoction improves diastolic function in rats with heart failure with preserved ejection fraction induced by abdominal aorta constriction through cyclic guanosine monophosphate-dependent protein kinase Signaling Pathway. PG - 764-772 LID - 10.19852/j.cnki.jtcm.20220519.003 [doi] AB - OBJECTIVE: To determine whether Shunxin decoction improves diastolic function in rats with heart failure with preserved ejection fraction (HFpEF) by regulating the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway. METHODS: Except for control group 8 and sham surgery group 8, the remaining 32 male Sprague-Dawlay rats were developed into HFpEF rat models using the abdominal aorta constriction method. These rats in the HFpEF model were randomly divided into the model group, the Shunxin high-dose group, the Shunxin low-dose group, and the Qiliqiangxin capsule group. The three groups received high-dose Shunxin decoction, low-dose 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-proBNP). 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 cGMP-PKG pathway. Natriuretic peptide receptor A (NPRA) and guanylate cyclase (GC) were detected by immunohistochemistry, and eNOS, phosphodiesterase 5A (PDE5A), and cGMP-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 ( < 0.01). Furthermore, Shunxin decoction high-dose group E/A value was decreased ( < 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 ( < 0.01). Compared to the model group, the expressions of eNOS and PKG I increased ( < 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 ( < 0.01). CONCLUSIONS: Shunxin decoction can improve diastolic function in rats with HFpEF. It increases the expression of NPRA, GC, and eNOS in the myocardial cell cGMP-PKG signaling pathway, upregulates cGMP expression, decreases PDE5A expression to reduce the cGMP degradation. Thus, the cGMP continually stimulates PKG I, reversing myocardial hypertrophy and improving myocardial compliance in HFpEF rats. FAU - Jiaying, Zhang AU - Jiaying Z AD - School of basic medical sciences, Institute of Integrated Chinese and Western Medicine,Lanzhou University, Lanzhou 730000, China. FAU - Xiangxiang, Wei AU - Xiangxiang W AD - School of basic medical sciences, Institute of Integrated Chinese and Western Medicine,Lanzhou University, Lanzhou 730000, China. FAU - Xuefeng, L I AU - Xuefeng LI AD - School of basic medical sciences, Institute of Integrated Chinese and Western Medicine,Lanzhou University, Lanzhou 730000, China. FAU - Yang, Yuan AU - Yang Y AD - School of basic medical sciences, Institute of Integrated Chinese and Western Medicine,Lanzhou University, Lanzhou 730000, China. FAU - Yinghuan, Dou AU - Yinghuan D AD - School of basic medical sciences, Institute of Integrated Chinese and Western Medicine,Lanzhou University, Lanzhou 730000, China. FAU - Yanbin, Shi AU - Yanbin S AD - School of basic medical sciences, Institute of Integrated Chinese and Western Medicine,Lanzhou University, Lanzhou 730000, China. FAU - Ping, Xie AU - Ping X AD - Department of Cardiology, Gansu Provincial hospital, Lanzhou 730000, China. FAU - Mengru, Zhou AU - Mengru Z AD - School of basic medical sciences, Institute of Integrated Chinese and Western Medicine,Lanzhou University, Lanzhou 730000, China. FAU - Junnan, Zhao AU - Junnan Z AD - School of basic medical sciences, Institute of Integrated Chinese and Western Medicine,Lanzhou University, Lanzhou 730000, China. FAU - Miao, L I AU - Miao LI AD - School of basic medical sciences, Institute of Integrated Chinese and Western Medicine,Lanzhou University, Lanzhou 730000, China. FAU - Shuwen, Zhang AU - Shuwen Z AD - School of basic medical sciences, Institute of Integrated Chinese and Western Medicine,Lanzhou University, Lanzhou 730000, China. FAU - Rui, Zhu AU - Rui Z AD - School of basic medical sciences, Institute of Integrated Chinese and Western Medicine,Lanzhou University, Lanzhou 730000, China. FAU - Ying, Tian AU - Ying T AD - School of basic medical sciences, Institute of Integrated Chinese and Western Medicine,Lanzhou University, Lanzhou 730000, China. FAU - Hao, Tan AU - Hao T AD - School of basic medical sciences, Institute of Integrated Chinese and Western Medicine,Lanzhou University, Lanzhou 730000, China. FAU - Feifei, Tian AU - Feifei T AD - School of basic medical sciences, Institute of Integrated Chinese and Western Medicine,Lanzhou University, Lanzhou 730000, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - J Tradit Chin Med JT - Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan JID - 8211546 RN - 85-32-5 (Guanosine Monophosphate) RN - EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases) RN - H2D2X058MU (Cyclic GMP) SB - IM MH - Animals MH - Aorta, Abdominal/metabolism MH - Constriction MH - Cyclic GMP/metabolism MH - Cyclic GMP-Dependent Protein Kinases/genetics/metabolism MH - Diastole MH - Guanosine Monophosphate MH - *Heart Failure/drug therapy/genetics MH - Male MH - Rats MH - Signal Transduction MH - Stroke Volume/physiology PMC - PMC9924685 OTO - NOTNLM OT - Shunxin decoction OT - cyclic GMP-dependent protein kinases OT - diastole OT - heart failure OT - preserved ejection fraction OT - signal transduction EDAT- 2022/09/10 06:00 MHDA- 2022/09/14 06:00 PMCR- 2022/10/15 CRDT- 2022/09/09 11:23 PHST- 2022/09/09 11:23 [entrez] PHST- 2022/09/10 06:00 [pubmed] PHST- 2022/09/14 06:00 [medline] PHST- 2022/10/15 00:00 [pmc-release] AID - 1662090424048-978278018 [pii] AID - 10.19852/j.cnki.jtcm.20220519.003 [doi] PST - ppublish SO - J Tradit Chin Med. 2022 Oct;42(5):764-772. doi: 10.19852/j.cnki.jtcm.20220519.003.