肝螺杆菌感染促进四氯化碳导致的BALB/c小鼠肝纤维化研究

Helicobacter hepaticus infection promotes liver fibrosis induced by carbon tetrachloride in BALB/c mice

为探讨肝螺杆菌(Helicobacter hepaticus,H.h)感染对四氯化碳(CCl_(4))致BALB/c小鼠肝纤维化病程的影响,选取5~6周龄雄性BALB/c小鼠40只,随机分为4组(对照组、H.h组、CCl_(4)组、H.h+CCl_(4)组)。H.h和CCl_(4)组分别采用灌胃法和腹腔注射法处理,分别于H.h感染后4和12周进行采样,检测各组小鼠血清中丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)含量,分别采用HE染色、天狼猩红染色、免疫组化法和实时荧光定量PCR(RT-qPCR)检测小鼠肝脏纤维化情况。结果显示:处理4周时,CCl_(4)组和H.h+CCl_(4)组小鼠出现轻度肝纤维化,其他组未见明显病变;处理12周时,与H.h组相比,H.h+CCl_(4)组小鼠肝脏中H.h活菌量显著升高(P>0.01),血清中ALT和AST均显著升高(P>0.01),肝脏中大量胶原纤维沉积,炎症和纤维化相关因子转录水平显著升高(P>0.01)。研究表明,H.h可加剧CCl_(4)诱导的BALB/c小鼠肝纤维化。

To elucidate the pathological effect of helicobacter hepaticus(H.h)on the progression of hepatic fibrosis induced by carbon tetrachloride(CCl_(4))infection in BALB/c mice.Forty 5-6 week-old male BALB/c mice were randomly divided into control group,H.h group,CCl_(4) group and H.h+CCl_(4) group.H.h and CCl_(4) were treated by gavage and intraperitoneal injection respectively,and sacrificed at 4 or 12 weeks post of inoculation.Alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in the serum were examined in different group.Tissue section observation and quantitative real time PCR(qRT-PCR)were conducted to evaluate liver fibrosis in the liver.After 4 weeks of treatment,mild liver fibrosis was observed in CCl_(4) group and H.h+CCl_(4) group,while no lesions were observed in other groups.H.h in the livers of mice in the H.h+CCl_(4) group were significantly higher than those in the H.h group after 12 weeks of infection.The serum levels of ALT and AST were significantly higher in the H.h+CCl_(4) groups compared with that in the other three group,extensive collagen fiber deposition was shown,and transcription levels of inflammatory and fibrosis related factors were significantly increased.In conclusion,our data suggest that H.h infection could be an important contributing infectious factor to the development of CCl_(4) liver fibrosis.