Fasudil exerts a protective effect on down-regulation of IL-6 expression by inhibiting the NOTCH signaling pathway in EAM mice

Yanjun LI; Yuxing Wang; Jiakai Yang; Peijun Zhang; Wanrong LI; Wei Zhang; Yangqing Liu; Nianping Zhang

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Fasudil exerts a protective effect on down-regulation of IL-6 expression by inhibiting the NOTCH signaling pathway in EAM mice

VernacularTitle:Fasudil在EAM小鼠中通过抑制NOTCH信号通路下调IL-6表达
Author: Yanjun LI ¹ ; Yuxing WANG ² ; Jiakai YANG ¹ ; Peijun ZHANG ¹ ; Wanrong LI ¹ ; Wei ZHANG ¹ ; Yangqing LIU ¹ ; Nianping ZHANG ¹
Author Information

1. Institute of Immunology, Shanxi Datong University School of Medicine, Datong 037009
2. Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences of Shandong University, Jinan 250012, China
Publication Type:Journal Article
Keywords: Fasudil; experimental autoimmune myocarditis; NOTCH signaling pathway; IL-6
From: Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(1):82-88
CountryChina
Language:Chinese
Abstract: 【Objective】 To explore the effect and mechanism of Fasudil in the treatment of experimental autoimmune myocarditis (EAM) in mice so as to provide a theoretical basis for the clinical use of Fasudil in treating myocarditis. 【Methods】 Balb/c male mice were used as the research objects, and the EAM mice model was constructed using MyHC-α614-629 polypeptide. Mononuclear cells were isolated and cultured to detect the number of mononuclear cells in mouse spleen. Inflammation infiltration, fibrosis and IL-6 expression in mouse myocardial tissue were detected by HE staining, Masson staining and immunohistochemistry, respectively. The protein expressions of Notch1 and IL-6 were detected by Western blotting. qRT-PCR was used to detect the expressions of pro-inflammatory factors (IL-1α, IL-1β and IL-6) as well as key genes of TLRs and NOTCH signaling pathway. 【Results】 EAM mice showed increased HW, decreased BW, increased HW/e-BW, and increased inflammatory infiltration and fibrosis in myocardial tissue. The above-mentioned symptoms or pathological features were improved in EAM mice treated with Fasudil. The analysis showed that the pro-inflammatory factors IL-1α, IL-1β and IL-6 in the myocardial tissue of EAM mice were significantly increased, but only the expression of IL-6 was statistically different after Fasudil treatment compared with the control group. In addition, TLRs signaling pathway might also play an important role in the EAM mice treated with Fasudil. The expressions of IL-6 and Notch1 were consistent, and the expressions of the key genes of NOTCH signaling pathway (Notch1, Hes1 and Jag2) were down-regulated after Fasudil treatment. 【Conclusion】 Fasudil exerts a protective effect on down-regulation of IL-6 expression by inhibiting the NOTCH signaling pathway in EAM mice.