Therapeutic effect of neonatal mouse Cytomegalovirus hepatitis by CpG Oligodeoxynucleotide 2395
10.3760/cma.j.issn.2095-428X.2014.02.007
- VernacularTitle:含有CpG基序的寡聚脱氧核苷酸2395对鼠巨细胞病毒肝炎新生小鼠的治疗作用
- Author:
Zhao-Jun PAN
1
;
Li ZHOU
;
Jun WANG
;
Liangrong HAN
;
Yang CAO
;
Xueyuan WAN
;
Lingjian MENG
Author Information
1. 扬州大学医学院附属淮安市妇幼保健院新生儿科
- Keywords:
Cytomegalovirus;
CpG Oligodeoxynucleotide 2395;
Hepatitis;
Mouse
- From:
Chinese Journal of Applied Clinical Pediatrics
2014;29(2):104-109
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the treatment effects of newborn mice murine Cytomegalovirus (MCMV) hepatitis by using CpG Oligodeoxynucleotide 2395 (CpG ODN2395).Methods Specific pathogen-free BALB/c newborn mice were divided into 3 groups according to the broods randomly:control group,virus group and treatment group.In control group 9 g/L sodium chloride 20 × 10-6 L was intraperitoneally injected every other day.In virus group MCMV (TCID50 =108.31/L) 20 × 10-6 L was intraperitoneally injected once and 9 g/L sodium chloride solution 20 × 10-6 L was intraperitoneally injected every other day.In treatment group murine MCMV(TCID50 =10S31/L) 20 × 10-6 L was intraperitoneally injected once and from the first day CpG ODN2395 20 mg/kg was intraperitoneally injected every other day.Growths and development of mice were observed.Murine body weights were measured.Pathology of livers was observed by means of hematoxylin and eosin stain.The levels of serum ALT and IFN-α were measured by adopting enzyme linked immunosorbent assay.MCMV loads in liver were measured by way of polymerase chain reaction.The expression levels of IFN-α mRNA in liver were detected by using reverse transcription polymerase chain reaction.The expression levels of Toll-like receptor 9 (TLR9) and myeloid cell differentiation factor 88 (MyD88) in liver were detected by adopting Western blot.The results were analyzed by using SPSS 16.0 statistics software.Results 1.Compared with control group and treatment group,growth and development of virus group mice fell behind and on day 7,14 body weights were lowest(F =18.919,25.543,all P ＜ 0.05).Growth and development of treatment group mice were between control group and virus group.Body weights of treatment group mice were lower than those of control group,and there was statistical difference on day 7 (t =3.187,P ＜ 0.05).2.Compared with control group and treatment group,the levels of ALT in virus group was highest.ALT levels of treatment group were higher than those of control group and treatment group(F =11.407,11.791,154.656,all P ＜ 0.05).3.The pathologic change of liver tissue:the HAI of virus group reached the peak on day 3,then decreased gradually.The HAI of treatment group also reached the peak on day 3,but liver damage was obviously less than those of virus group.The liver damage also relieved gradually and the mean of HAI was obviously lower than that of virus group on day 7 and 14.4.MCMV DNA in liver was negative at control group.The magnitude of viral loading in livers of virus group was higher than that of treatment group.5.The levels of IFN-α in treatment group and virus group reached a peak on day 3 and declined gradually on day 7,14.The levels of IFN-α on treatment group were higher than that of virus group and control group.The levels of IFN-α virus group were higher than those of control group,but had no statistical difference.6.The mRNA expression of IFN-α in livers of treatment group and virus group began to increase on day 3 and reached a peak on day 7,and declined on day 14.The mRNA expression of IFN-α was higher than that of virus group and control group.The mRNA expression of virus group was higher than that of control group.7.The expressions of TLR9 and MyD88 in livers of treatment group were higher than that of virus group and control group.The expressions of TLR9 and MyD88 of virus group were higher than those of control group.Conclusions CpG ODN2395 can obviously improved liver function and histopathological lesions and reduce MCMV DNA load within liver tissues as well.CpG ODN2395 can improve the expression levels of TLR9 in liver and activate secretion interferon alpha by MyD88-dependent pathway,which were likely to play an important role in its treatment of murine CMV infection.
