炙甘草汤对实验性自身免疫性心肌炎的治疗作用及机制研究

目的 探讨炙甘草汤对实验性自身免疫性心肌炎的疗效及可能的作用机制.方法 40只BALB/c鼠随机分成空白对照组、实验性自身免疫性心肌炎(EAM)组、炙甘草汤组及强的松组各10只.采用重组α肌球蛋白重链多肽(MyHC-α)诱导小鼠制备实验性自身免疫性心肌炎(EAM)模型.将弗氏佐剂与MyHC-α等体积混合,分别在第0 d...

Therapeutic effects and mechanisms of Zhigancao Decoction on experimental autoimmune myocarditis

Objective To explore the therapeutic effects and possible mechanisms of Zhigancao Decoction on experimental autoimmune myocarditis.Methods Forty BALB/c mice were randomly divided into a blank control group,experimental autoimmune myocarditis(EAM)group,a Zhigancao Decoction group,and a prednisone group(n=10 each).The experimental autoimmune myocarditis(EAM)model was created by inducing mice with recombinant alpha myosin heavy chain polypeptide(MyHC alpha).Freund's adjuvant was mixed with an equal volume of MyHC-αand was intraplantar injected into the EAM group,Zhigancao Decoction group and prednisone group on days 0 and 7,respectively,and the blank control group was injected with an equal volume of Freund's adjuvant.From day 8,the Zhigancao Decoction group was treated with Zhigancao Decoction(22.76 g/kg,1/d),the prednisone group was administered prednisone(7.6 mg/kg,1/d),whereas mice in the blank control group and the EAM group received an equal volume of saline.HE staining was utilized to observe the pathological changes in the myocardial tissues of mice in each group after continued administration for 14 days.Levels of cytokines interferon-gamma(IFN-γ),interleukin 4(IL-4),interleukin 17a(IL-17A),interleukin 10(IL-10),interleukin 1 alpha(IL-1α),interleukin 6(IL-6),and tumour necrosis factor-alpha(TNF-α)were measured in myocardial tissue homogenates by flow cytometric multiplex protein quantification.The distribution of CD4+T cell subsets in the spleen of each group was detected by flow cytometry.Results Mice in the EAM group exhibited typical myocarditis changes,endocardial surface discolouration and extensive myocardial inflammatory cell infiltration by HE staining of myocardial tissue sections after immunization.The levels of cytokines IFN-γ,IL-1α,and IL-6 in myocardial homogenates of mice in the EAM group were all significantly increased compared with those in the blank control group (P<0.05). The levels of helper 1 (Th1) and helper 17 (Th17) cells in the spleen were also significantly increased compared with the blank control after immunization (P<0.05), but the levels of helper 2 (Th2) cells did not change significantly. Zhigancao Decoction group significantly attenuated the inflammatory response in myocardial tissue, the levels of cytokines IFN-γ, IL-6, and IL-1α in the heart were all significantly decreased compared with the EAM group (P<0.05), and the levels of Th1 and Th17 cells in the spleen were also significantly decreased compared with the EAM group (P<0.05). Conclusion Zhigancao Decoction in the development of EAM is able to attenuate inflammatory responses and combat EAM by reducing activated inflammatory cells as well as inhibiting inflammatory cytokine secretion in the myocardium, thereby improving myocardial inflammatory responses and reducing myocardial injury.