The Role Of Atorvastatin On Immune Function Of BALB/c Mice Infected With P.y 17XL

Objective:To investigate the immunomodulatory effects of atorvastatin(AVA)on BALB/c mice infected with lethal Plasmodium yoelii 17XL(P.y 17XL).Methods:BALB/c mice infected with P.y 17XL were used as subjects.The infection rate and survival rate of mice were observed dynamically by instilling d0 atorvastatin(3mg/kg/d)for 8 days.Flow cytometry was used to detect the number of hepatic lymphocytes,IFN-γsecretion levels,CXCR3,CXCR6,NKG2D and GB expression.qPCR was used to detect the expression of spleen and liver tissue chemokines CXCL9,CXCL10,CXCL11 and CXCL16.Results:After P.y 17XL infection d7,the protozoa in the control group increased rapidly to 61.8%,and the infection rate in the AVA group was 41.2%,which was significantly lower than that in the control group(P<0.05).The peak of protozoa in the AVA group was delayed.Flow cytometry results showed that the levels of CD3~+,CD4~+and CD8~+T cells in the AVA group were significantly increased(P<0.05),and the number of NK cells in the spleen was significantly increased(P<0.01).The expression of CXCR6 in liver CD4~+T,CD8~+T and NKT cells was significantly up-regulated in AVA group(P<0.05,P<0.01,P<0.05),and the expression of CXCR6 in spleen CD4~+T cells was increased(P<0.001).CXCR3 increased expression in spleen CD4~+T cells(P<0.05)and Treg cells(P<0.01)in AVA group.The expression of IFN-γwas increased in spleen CD4~+T(P<0.05)and NK cells(P<0.01),and the expression of IFN-γwas increased in liver CD8~+T cells(P<0.05).The expression of granzyme B in spleen CD8~+T(P<0.05)and NKT cells(P<0.01)was increased in AVA group.The expression of NKG2D in CD8~+T cells and NKT cells was significantly increased(P<0.05).The number of liver CD8~+NKG2D~+T cells in the AVA group was increased,and the expression of NKG2D in NKT was increased(P<0.05).qPCR results showed that compared with the control group,the spleen CXCL9(P<0.01)and CXCL11(P<0.001)mRNA levels were decreased in the AVA group,liver CXCL9(P<0.001),CXCL10(P<0.001),CXCL11(P<0.01).mRNA expression is reduced.Conclusion:1.AVA treatment regulates the expression levels of spleen and liver chemokines CXCL9-11 and CXCL16,affecting CXCR3~+cells and CXCR6~+cells distributed in tissues,which promotes the clearance of malaria parasites.2.AVA treatment plays an important role in improving the pathological damage of liver in malaria.