内源性Relaxin-1 Relaxin-3及其受体LGR7表达水平在小鼠心房颤动心肌纤维化中的作用

doi:10.3969/j.issn.1006-6233.2021.07.002

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Abstract Objective: To analyze the role of endogenous relaxin (RLX)-1, relaxin-3 and relaxin receptor (LGR7) in myocardial fibrosis of mice with atrial fibrillation. Methods: Atrial fibrillation model was constructed by intraperitoneal injection of ISO. 40 C57B62 mice were randomly divided into blank control group, model group, model group + RLX1 and model group + RLX3 group with 10 mice in each group. The model group + RLX1 and model group + RLX3 were intraperitoneally injected with RLX1 and RLX3, respectively. The blank control group and model group were injected with the same volume of normal saline. A week later, the area of myocardial collagen deposition and the content of hydroxyproline were detected. RT-PCR and Western Blot were used to detect the mRNA and protein expression of relaxin 1, relaxin 3 and LGR7. Immunohistochemical method was used to detect α-SMA integral optical density (IOD), and Western Blot was used to detect the expression of α-SMA protein in myocardial tissues. Real-time PCR and Western Blot were used to detect the mRNA and protein expression of collagenⅠ, collagen III, matrix metalloproteinase-1 (MMP-1), MMP-2, MMP-9, MMP-13, and tissue inhibitor of metalloproteinase-1 (TIMP-1). Meanwhile, RT-PCR method was used to detect the mRNA expression of myocardial angiotensin II (AngII), angiotensin receptor 1 (AT1R), angiotensin receptor 2 (AT2R), aldosterone (ALD) and mineralocorticoid receptor (MR). Results: ①Compared with the blank control group, the percentages of myocardial collagen deposition areas in ventricular septum, right ventricle and left ventricle, and the content of hydroxyproline were significantly increased in the model group (P<0.05). Compared with the model group, the percentages of myocardial collagen deposition areas in ventricular septum, right ventricle and left ventricle, and the content of hydroxyproline were significantly reduced in the model group+RLX1 and model group+RLX3 (P<0.05). ②Compared with the blank control group, the mRNA and protein expression of relaxin 1, relaxin 3 and LGR7 was significantly reduced in the model group (P<0.05). Compared with the model group, the mRNA and protein expression of relaxin 1, relaxin 3 and LGR7 was significantly increased in model group +RLX1 and model group+RLX3 (P<0.05). ③Compared with the blank control group, α-SMA IOD, α-SMA protein, the mRNA and protein expression of collagenⅠ and collagenⅢ were significantly increased in the model group (P<0.05). Compared with the model group, α-SMA IOD, α-SMA protein, the mRNA and protein expression of collagenⅠ and collagenⅢ were significantly reduced in the model group+RLX1 and the model group+RLX3 (P<0.05). ④Compared with the blank control group, the mRNA and protein expression of MMP-1, MMP-2, MMP-9 and MMP-13 was significantly increased, while the expression of TIMP-1 mRNA and protein was significantly reduced in the model group (P<0.05). Compared with the model group, the mRNA and protein expression of MMP-1, MMP-2, MMP-9 and MMP-13 was significantly decreased, while the expression of TIMP-1 mRNA and protein was significantly increased in the model group+RLX1 and model group+RLX3 (P<0.05). ⑤Compared with the blank control group, the levels of Ang Ⅱ mRNA, AT1R mRNA, AT2R mRNA, ALD mRNA, and MR mRNA were significantly increased in the model group. Compared with the model group, the levels of Ang Ⅱ mRNA, AT1R mRNA, AT2R mRNA, ALD mRNA, and MR mRNA were significantly reduced in the model group+RLX1 and model group+RLX3. Conclusion: The pathological changes of myocardial fibrosis are observed in the heart of the AF mice, and the endogenous relaxin-1, relaxin-3 and LGR7 are low expression, and relaxin could be antagonized by AngII and ALD system.

Key words： Atrial fibrillation Myocardial fibrosis Relaxin-1 Relaxin-3 Relaxin receptor

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2021.07.002 OR http://www.hbyxzzs.cn/EN/Y2021/V27/I7/1063

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