Zhang Xian, Shao Ze, Ni Yuchao, Chen Feilong, Yu Xia, Wen Jiasheng
Cardiology Department, Kunshan Hospital of Integrated Traditional Chinese and Western Medicine, Kunshan, Jiangsu 215332, P.R. China.
Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China.
Exp Ther Med. 2023 Sep 27;26(5):527. doi: 10.3892/etm.2023.12226. eCollection 2023 Nov.
The clinical incidence of congestive heart failure (CHF) is very high and it poses a significant threat to the health of patients. The traditional Chinese medicine monomer salsolinol is widely used to treat similar symptoms of CHF. However, there have been no reports on the effect of salsolinol for the management of CHF and its effects on myocardial fibrosis. In the present study, salsolinol was used to treat angiotensin II (AngII)-induced human cardiac fibroblasts (HCFs) and cell proliferation and migration were assessed using a CCK-8, EdU staining assay and wound healing assay. Subsequently, immunofluorescence, western blotting and other techniques were used to detect indicators associated with cell fibrosis and relevant kits were used to detect markers of cellular inflammation and reactive oxygen species (ROS) production. Molecular docking analysis was used to predict the relationship between salsolinol and lysine-specific histone demethylase 1A (LSD1). Subsequently, the expression of LSD1 in the serum of CHF patients was detected by reverse transcription-quantitative PCR. Finally, LSD1 was overexpressed in cells to explore the regulatory mechanism of salsolinol in AngII-induced HFCs. Salsolinol reduced the proliferation and migration. Salsolinol reduced the expression of fibrosis marker proteins α-smooth muscle actin, Collagen I and Collagen III in a concentration-dependent manner, thereby reducing cell fibrosis. In addition, salsolinol reduced the levels of TNF-α and IL-6 in the cell supernatant and ROS production following AngII induction. Salsolinol inhibited LSD1 expression and regulated the STAT3/Notch-1 signaling pathway. Upregulation of LSD1 reversed the effects of salsolinol on AngII-induced HCFs. Salsolinol inhibited LSD1 via regulation of the STAT3/Notch-1 signaling pathway to improve Ang II-induced myocardial fibrosis .
充血性心力衰竭（CHF）的临床发病率非常高，对患者的健康构成重大威胁。中药单体去甲猪毛菜碱被广泛用于治疗CHF的类似症状。然而，关于去甲猪毛菜碱对CHF的治疗效果及其对心肌纤维化的影响尚无报道。在本研究中，使用去甲猪毛菜碱处理血管紧张素II（AngII）诱导的人心脏成纤维细胞（HCFs），并使用CCK-8、EdU染色试验和伤口愈合试验评估细胞增殖和迁移。随后，采用免疫荧光、蛋白质印迹等技术检测与细胞纤维化相关的指标，并使用相关试剂盒检测细胞炎症和活性氧（ROS）产生的标志物。采用分子对接分析预测去甲猪毛菜碱与赖氨酸特异性组蛋白去甲基化酶1A（LSD1）之间的关系。随后，通过逆转录定量PCR检测CHF患者血清中LSD1的表达。最后，在细胞中过表达LSD1以探索去甲猪毛菜碱在AngII诱导的HFCs中的调节机制。去甲猪毛菜碱降低了细胞增殖和迁移。去甲猪毛菜碱以浓度依赖性方式降低纤维化标志物蛋白α-平滑肌肌动蛋白、I型胶原蛋白和III型胶原蛋白的表达，从而减少细胞纤维化。此外，去甲猪毛菜碱降低了AngII诱导后细胞上清液中TNF-α和IL-6的水平以及ROS的产生。去甲猪毛菜碱抑制LSD1表达并调节STAT3/Notch-1信号通路。LSD1的上调逆转了去甲猪毛菜碱对AngII诱导的HCFs的作用。去甲猪毛菜碱通过调节STAT3/Notch-1信号通路抑制LSD1，从而改善Ang II诱导的心肌纤维化。
