Yao Ting-Ting, Yang Hong-Xia, Sun Jia-Huan, Zhang Yue, Zhang Yu, Song Qiu-Hang, Liu Wei-Zhe, Zhang Juan-Juan, Li Ai-Ying
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, China.
Hebei Key Laboratory of Chinese Medicine Research on Cardio-cerebrovascular Disease, Shijiazhuang 050091, Hebei, China.
Evid Based Complement Alternat Med. 2022 May 9;2022:6841276. doi: 10.1155/2022/6841276. eCollection 2022.
Myocardial fibrosis is the main morphological change of ventricular remodelling caused by cardiovascular diseases, mainly manifested due to the excessive production of collagen proteins. SRY-related high mobility group-box gene 9 (SOX9) is a new target regulating myocardial fibrosis. Bellidifolin (BEL), the active component of , can prevent heart damage. However, it is unclear whether BEL can regulate SOX9 to alleviate myocardial fibrosis. The mice were subjected to isoproterenol (ISO) to establish myocardial fibrosis, and human myocardial fibroblasts (HCFs) were activated by TGF-1 in the present study. The pathological changes of cardiac tissue were observed by HE staining. Masson staining was applied to reveal the collagen deposition in the heart. The measurement for expression of fibrosis-related proteins, SOX9, and TGF-1 signalling molecules adopted Western blot and immunohistochemistry. The effects of BEL on HCFs, activity were detected by CCK-8. The result showed that BEL did not affect cell viability. And, the data indicated that BEL inhibited the elevations in -SMA, Collagen I, and Collagen III by decreasing SOX9 expression. Additionally, SOX9 suppression by siRNA downregulated the TGF-1 expression and prevented Smad3 phosphorylation, as supported by reducing the expression of -SMA, Collagen I, and Collagen III. In vivo study verified that BEL ameliorated myocardial fibrosis by inhibiting SOX9. Therefore, BEL inhibited SOX9 to block TGF-1 signalling activation to ameliorate myocardial fibrosis.
心肌纤维化是心血管疾病引起的心室重构的主要形态学变化，主要表现为胶原蛋白过度产生。SRY相关高迁移率族盒基因9（SOX9）是调节心肌纤维化的新靶点。灯盏花乙素（BEL）是[具体植物名称]的活性成分，可预防心脏损伤。然而，BEL是否能通过调节SOX9来减轻心肌纤维化尚不清楚。在本研究中，小鼠通过异丙肾上腺素（ISO）诱导建立心肌纤维化模型，人心脏成纤维细胞（HCFs）则用转化生长因子-β1（TGF-β1）激活。通过苏木精-伊红（HE）染色观察心脏组织的病理变化。采用Masson染色来显示心脏中的胶原沉积。采用蛋白质免疫印迹法和免疫组织化学法检测纤维化相关蛋白、SOX9和TGF-β1信号分子的表达。通过CCK-8检测BEL对HCFs活性的影响。结果显示BEL不影响细胞活力。并且，数据表明BEL通过降低SOX9表达抑制α-平滑肌肌动蛋白（α-SMA）、I型胶原蛋白和III型胶原蛋白的升高。此外，小干扰RNA（siRNA）抑制SOX9可下调TGF-β1表达并阻止Smad3磷酸化，这也通过降低α-SMA、I型胶原蛋白和III型胶原蛋白的表达得到证实。体内研究证实BEL通过抑制SOX9改善心肌纤维化。因此，BEL通过抑制SOX9阻断TGF-β1信号激活来改善心肌纤维化。
