ABSTRACT
Objective:To clarify the anti-inflammatory effects and anti-endoplasmic reticulum stress effects of resolvin D2 (RvD2) in viral myocarditis mice and to explore its possible mechanism.Methods:Fifty male BALB/c mice were collected and assigned corresponding numbers. Then 40 male BALB/c mice were selected randomly with 10 mice in each group. They were set as normal control group, RvD2 control group, viral myocarditis group and RvD2 treatment group. Afterwards, mice in the RvD2 control group received continuous intraperitoneal injection of RvD2 for 7 days, while mice in the viral myocarditis group received intraperitoneal injection of Coxsackievirus B3 virus (CVB3) in the purpose of constructing an animal model of viral myocarditis. Then, mice in the RvD2 treatment group were given continuous intraperitoneal injection of RvD2 for 7 days. After these 7 days, the mice of each group were sacrificed and their cardiac tissue and serum samples were taken. The expression levels of serum inflammatory factors including IL-1β and TNF-α were detected by ELISA in each group of mice, and HE staining were used to detect the inflammatory cell infiltration in myocardial tissue of each group. Meanwhile, the expression levels of inflammation-related proteins IL-1β, TNF-α as well as endoplasmic reticulum stress-related proteins like GRP78 and Chop in the myocardial tissue in each group of mice were detected by Western blot experiment. The remaining 10 BALB/c mice were treated with intraperitoneal injection of RvD2 as well as GPR18 protein inhibitors after constructing the animal model of viral myocarditis mentioned above. In the end, the expression levels of GPR18 protein, inflammation-related proteins including IL-1β and TNF-α as well as endoplasmic reticulum stress-related proteins like GRP78 and Chop in the myocardial tissue of each group were detected by Western blot experiments.Results:Compared with the normal control group, the expression levels of inflammatory factors IL-1β and TNF-α in the serum of mice with viral myocarditis were significantly increased, and the degree of infiltration of inflammatory cells in myocardial tissue was also significantly increased. Besides, the expression levels of the inflammation-related proteins IL-1β, TNF-α as well as endoplasmic reticulum stress-related proteins including GRP78 and Chop increased largely. While compared with the viral myocarditis group, the expression levels of serum inflammatory factors IL-1β and TNF-α in the mice of the RvD2 treatment group were significantly reduced and the degree of infiltration of inflammatory cells in the cardiac tissue was significantly reduced. Also, the expression levels of inflammation-related proteins IL-1β and TNF-α as well as endoplasmic reticulum stress-related proteins GRP78 and Chop were significantly reduced. After intraperitoneal injection of RvD2 and GPR18 inhibitor, in the mice treated with viral myocarditis, the expression levels of IL-1β, TNF-α and endoplasmic reticulum stress-related proteins like GRP78 and Chop in myocardial tissue of these mice significantly increased when it came to compare with the RvD2 treatment group, while the expression levels of GPR18 protein were significantly reduced.Conclusions:RvD2 can inhibit the inflammatory response and endoplasmic reticulum stress injury in mice with viral myocarditis by binding to the membrane protein receptor GPR18, thus exerting a protective effect on heart.