Effect of bicyclol-mediated N6-methyladenosine methylation on myocardial fibrosis in rats
10.3969/j.issn.1009-0126.2024.10.020
- VernacularTitle:双环醇介导N6-甲基腺苷甲基化修饰影响大鼠心肌纤维化的作用研究
- Author:
Yuechang LI
1
;
Tongtong XU
;
Xiangwei LÜ
;
Weikun ZHAO
;
Qiuyu QIN
;
Liqin CHEN
Author Information
1. 541001 桂林医学院附属医院综合科医疗保健病区
- Keywords:
methylation;
myocardial fibrosis;
rats,Sprague-Dawley;
bicyclol
- From:
Chinese Journal of Geriatric Heart Brain and Vessel Diseases
2024;26(10):1210-1214
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the therapeutic effect of bicyclol(BIC)on rat model of myocardial fibrosis and its possible mechanism.Methods Twenty-four SPF male SD rats were randomly di-vided into sham group,model group,low-and high-dose groups,with 6 rats in each group.Except for the sham group,all other groups were injected with 5 mg/(kg·d)isoproterenol by tail vein to establish myocardial fibrosis model,and the low-and high-dose groups were administered by ga-vage with 100 and 200 mg/(kg·d)BIC,respectively for 14 consecutive days.HE staining and Masson staining were used respectively to observe the severity of myocardial injury and fibrosis.Western blot assay was employed to detect the protein expression of Collagen Ⅰ,Collagen Ⅲ,al-pha smooth muscle actin(α-SMA),methyltransferase-like protein 3(METTL3),α-ketoglutarate-dependent dioxygenase AlkB homolog 5(ALKBH5)and YTH domain family protein 1(YTHDF1)in rat myocardium.Results Compared with the sham group,myocardial cell necrosis and myocardial fibrosis were significantly more serious in the model group.Low-and high-dose BIC treatment reduced myocardial cell rupture and necrosis and myocardial fibrosis when com-pared with the model group.The expression levels of Collagen Ⅰ,Collagen Ⅲ,α-SMA,METTL3 and YTHDF1(P<0.05)were significantly higher,and that of ALKBH5(0.58±0.02 vs 0.88±0.07,P<0.05)was notably lower in the myocardial tissues of the model group than the sham group.While,both doses of BIC treatment significantly reversed above changes in protein levels(P<0.05).Conclusion BIC can effectively alleviate myocardial structural damage and interstitial collagen deposition in rats with isoproterenol-induced myocardial fibrosis,and its mechanism may be related to m6A methylation modification.