对乙酰氨基酚诱导的小鼠急性肝损伤过程中IL-6跨信号途径对PCNA表达的影响

Effect of IL-6 trans-signialing on expression of PCNA during acute liver injury induced by acetaminophen in mice

目的研究IL-6跨信号途径在对乙酰氨基酚(acetaminophen,AAP)诱导的小鼠急性肝损伤过程中对增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)表达的影响。方法健康BALB/c雄性小鼠24只,随机分为4组(A组、B组、C组、D组),A组小鼠腹腔注射0.1 ml的PBS,B、C、D组小鼠均按500 mg/kg腹腔注射AAP溶液0.1 ml,C组小鼠提前1 h腹腔注射0.1 ml浓度为10μg/ml的IL-6跨信号途径的抑制剂sgp130Fc,D组小鼠提前1 h腹腔注射0.1 ml浓度为0.5μg/ml的IL-6跨信号途径的激动剂Hyper-IL-6。48 h后处死小鼠取肝脏,HE染色观察各组小鼠肝脏损伤情况,免疫组化法检测各组小鼠肝脏中PCNA的表达情况。结果与B组比较,C组小鼠肝脏损伤加重,D组小鼠肝脏损伤减轻。B、C、D组PCNA表达量明显高于A组(P<0.01),C组PCNA表达量低于B组(P<0.01),D组PCNA表达量明显高于B组(P<0.01)。结论 IL-6跨信号途径在AAP诱导的小鼠急性肝损伤过程中促进PCNA的表达,它可能有减轻肝脏损伤、保护肝脏的作用。

Objective To study the effect of IL-6 trans-signaling on expression of proliferating cell nuclear antigen （PCNA） during acute liver injury induced by acetaminophen （AAP） in mice. Methods Twenty-four healthy male BALB/c mice were randomly divided into 4 groups （ A, B, C and D）. The group A received intraperitoneal injection of 0. 1 ml PBS. The group B, C and D received intraperitoneal injection of 0.1 ml AAP （500 mg/kg）. The group C was treated intraperitoneal injection with 0.1 ml sgp130Fc （10 μg/ml）which exclusively inhibited IL-6 trans-signaling 1 h prior to AAP treatment. The group D was treated intraperitoneal injection with 0.1 ml Hyper-IL-6 （0.5 μg/ml） which kindled IL-6 trans-signaling 1 h prior to AAP treatment. The mice were sacrificed 48 h after the injection. The pathologi- cal changes of liver tissue were observed by HE staining, the expression of PCNA was detected by immunohistochemistry method. Results Compared with group B, the liver injury in group C was aggravated, the liver injury in group D was alleviated. The expression of PCNA in group B, C, D was significantly higher than that in group A （P 〈 0.01） , the expression of PCNA in group C was lower than that in group B （P 〈0.01 ） , the expression of PCNA in group D was significantly higher than that in group B （P 〈0.01）. Conclusion IL-6 trans-signaling promotes the expression of PCNA during acute liver injury induced by AAP in mice, it may play a protective role by alleviating liver injury.