RIG-I在新生小鼠巨细胞病毒肝炎中的表达及意义

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目的探讨维甲酸诱导基因I(RIG-I)在采用鼠巨细胞病毒(MCMV)诱导的新生BALB/c小鼠肝脏组织中的表达及其意义。方法 48只新生BALB/c小鼠随机分为正常对照组(NC组)和病毒组(MCMV组)各24只,MCMV组新生小鼠一次性腹腔注射MCMV20μl(TCID50:104.44/ml)方法建立肝病新生小鼠模型,NC组腹腔注射等量无菌生理盐水,分别于注射后3、7、14 d留取静脉血与肝脏组织(各8只)。PCR法检测肝脏组织中MCMV-DNA的表达,HE染色观察肝脏病理变化,RT-PCR法检测肝组织RIG-I的m RNA表达,Western blot法检测RIG-I的蛋白表达,ELISA法检测血清谷丙转氨酶(ALT)、I型干扰素IFN-β含量。结果 (1)成功建立了新生小鼠巨细胞病毒肝炎模型;(2)MCMV组小鼠肝脏组织HE染色可见明显病理损害,3 d肝细胞点状坏死,7 d大量炎性细胞浸润,片状坏死;NC组肝组织未见明显异常。(3)MCMV组ALT表达量在感染后3 d已明显升高,7 d达高峰,14 d有所下降,与对照组比较差异有统计学意义(P<0.05);RIG-I、IFN-β与ALT在3、7、14 d呈负相关(P<0.05)。结论 RIG-I参与了MCMV感染新生小鼠肝炎的发生、发展过程,肝脏中RIG-I、IFN-β表达越低肝损伤越重。推测MCMV感染后可能通过RIG-I介导的信号通路导致IFN-β分泌降低,使得MCMV在一定程度上获得免疫逃逸,成为MCMV肝炎致病机制之一。 Objective To investigate the expression and significance of retinoic acid-induced gene I (RIG-I) in liver tissue of neonatal BALB / c mice induced by murine cytomegalovirus (MCMV). Methods 48 neonatal BALB / c mice were randomly divided into normal control group (NC group) and virus group (MCMV group), 24 mice each. MCMV 20ml MCLV (TCID50: 104.44 / ml) Neonatal mouse model, NC rats were injected intraperitoneally with equal volume of sterile saline, and venous blood and liver tissues were collected at 3, 7 and 14 days after injection (8 rats each). The expression of MCMV-DNA in liver tissue was detected by PCR, the pathological changes of liver were observed by HE staining, the mRNA expression of RIG-I in liver tissue was detected by RT-PCR, the protein expression of RIG-I was detected by Western blot, Aminotransferase (ALT), type I interferon IFN-β content. Results (1) The newborn mouse model of cytomegalovirus hepatitis was established successfully. (2) The pathological changes of liver were observed in HE staining of MCMV mice. The hepatocytes were necrotic on day 3 and infiltrated by inflammatory cells Necrosis; no obvious abnormalities in NC group liver tissue. (3) The expression of ALT in MCMV group was significantly increased at 3 days after infection, reaching the peak on the 7th day and decreasing on the 14th day, the difference was statistically significant (P <0.05) β and ALT were negatively correlated at 3, 7 and 14 d (P <0.05). Conclusion RIG-I is involved in the pathogenesis and development of hepatitis in MCMV-infected neonatal mice. The lower the expression of RIG-I and IFN-β in liver is, the more severe hepatic injury. It is speculated that MCMV infection may lead to the decrease of IFN-β secretion through RIG-I-mediated signal pathway, which makes MCMV obtain immune escape to a certain extent and become one of the pathogenesis of MCMV hepatitis.
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