吉西他滨对小鼠实验性自身免疫性心肌炎的影响

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Abstract Objective: To study the therapeutic effect of gemcitabine on experimental autoimmune myocarditis (EAM) model mice. Methods: A total of 15 Balb／c mice were used to construct EAM model and divided into control group, EAM group, EAM+gemcitabine group(n=5 in each group). On the 21st day, the eyeballs blood were harvested and the mice were sacrificed by cervical dislocation. HE staining was performed to observe lymphocyte infiltration in the cardiac tissue, and the inflammation score was analyzed. Flow cytometry was used to detect the proportion of myeloidderived suppressor cell (MDSCs) and Th17 cells in spleen tissues; the concentration of IL17A in serum was detected by ELISA. The IL17A mRNA level in cardiac tissue was detected by qRTPCR. MDSC and Nave CD4+T cells were sorted from spleens of Balb／c mice, and divided into activation group, induction group, coculture group; the Th17 percentage in each group were detected by flow cytometry. Results: Compared with the control group, there was mainly inflammatory cell infiltration and myocardial necrosis in the myocardial tissue of the EAM group. Compared with the EAM group, the infiltration of inflammatory cells and myocardial necrosis were reduced in the EAM+gemcitabine group. Compared with the control group, the myocardial tissue inflammation score of EAM group was significantly increased(P<0.05). Compared with EAM group, the myocardial tissue inflammation score of EAM+Gemcitabine group was significantly lower(P<0.05). Compared with the control group, the ratio of MDSC and Th17 in the spleen of EAM group was significantly increased(P<0.05). Compared with EAM group, EAM+Gemcitabine group showed lower proportion of MDSC and Th17 cells in the spleen(P<0.05). Compared with the control group, the serum IL17A concentration and IL17A mRNA in the EAM group were significantly increased(P<0.05). Compared with EAM group, serum IL17A concentration and IL17A mRNA level in EAM+gemcitabine group were significantly lower(P<0.05). Compared with the induction group, the proportion of IL17A in the coculture group was significantly increased(P<0.05). Conclusion: In the EAM mouse model, gemcitabine may attenuate myocardial inflammation by inhibiting the amount of MDSC in the mouse spleen and the differentiation of Nave CD4+T cells into Th17 cells.

Received: 31 December 2018

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http://zzs.ujs.edu.cn/xbyxb/EN/ OR http://zzs.ujs.edu.cn/xbyxb/EN/Y2019/V29/I02/117

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