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| Effect of Peiminine B on myocardial fibrosis in diabetes rats by regulating Gas6/Axl signaling pathway |
| Hits 8 Download times 1 Received:July 12, 2024 |
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| DOI
10.11656/j.issn.1672-1519.2024.12.18 |
| Key Words
Peiminine B;growth arrest-specific protein 6/Axl signaling pathway;diabetes;myocardial fibrosis |
| Author Name | Affiliation | E-mail | | WANG Ruiqi | Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China | | | PANG Guoming | Department of Endocrinology, Kaifeng Hospital of Traditional Chinese Medicine, Kaifeng 475002, China | | | LI Li | Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China | 404460429@qq.com |
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| Abstract
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| [Objective] This study was designed to investigate the effects of Peiminine B（PMI） on myocardial fibrosis and growth arrest-specific protein 6（Gas6）/Axl signaling pathway in diabetes（DM） rats. [Methods] We constructed a DM rat model and randomly divided the successfully modeled rats into a DM group，a low-dose and high-dose PMI group（PMI-L，PMI-H group），and a high-dose PMI+pathway inhibitor R428 group（PMI-H+R428 group），with 12 rats in each group. Additionally，12 normal rats were regarded as the control group. Ultrasound was applied to examine the cardiac function indicators of rats in each group. An automatic blood analyzer was applied to detect fasting blood glucose（FBG） and serum creatine kinase isoenzyme（CK-MB），and lactate dehydrogenase（LDH） levels were detected in rats in each group. HE staining and Masson staining were applied to observe the pathological changes and fibrosis degree of myocardial tissue of rats in each group. TUNEL staining was applied to detect apoptosis in myocardial tissue cells. Immunohistochemistry was applied to detect the expression of collagen I（COL I） and collagen Ⅲ（COL Ⅲ）. Immunoblotting was applied to detect the expression of Gas6 and p-Axl/Axl. [Results] Compared with the Control group，the DM group had myocardial fiber rupture，disordered arrangement of myocardial cells，cell hypertrophy，nuclear pyknosis and deep staining，obvious infiltration of inflammatory cells，decreased cell count，increased deposition of blue collagen fibers，and disordered arrangement with scattered distribution，the LVEDD，LVESD，levels of FBG，CK-MB，LDH，and expression of COL I and COL Ⅲ elevated，the expression of LVFS and Gas6，p-Axl/Axl reduced（P<0.05）. The arrangement of myocardial fibers in the PMI-L and PMI-H groups was relatively neat compared to the DM group，with relatively normal cell morphology，reduced inflammatory cell infiltration，increased cell count，reduced fibrosis，reduced deposition of blue collagen fibers，and relatively neat cell arrangement，the LVEDD，LVESD，levels of FBG，CK-MB，LDH，and expression of COL I and COL Ⅲ reduced，the expression of LVFS and Gas6，p-Axl/Axl increased（P<0.05）. The pathological damage to myocardial tissue in the PMI-H+R248 group was more severe than that in the PMI-H group，with obvious infiltration of inflammatory cells and fibrosis of myocardial tissue，the deposition of blue collagen fibers was increased，the LVEDD，LVESD，levels of FBG，CK-MB，LDH，and expression of COL I and COL Ⅲ increased，the expression of LVFS and Gas6，p-Axl/Axl reduced（P<0.05）. [Conclusion] Peiminine B can inhibit myocardial fibrosis in diabetes rats，and its mechanism is related to the activation of GAS6/Axl signaling pathway. |
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