白藜芦醇调控Th1和Th2应答抑制小鼠日本血吸虫病肝脏纤维化的研究

Resveratrol inhibited hepatic fibrosis in mice with schistosomiasis japonica by modulating Th1 and Th2 responses

目的探讨白藜芦醇对日本血吸虫病纤维化的作用,并分析其对Th1和Th2应答的影响。方法 45只C57BL/6小鼠感染日本血吸虫3周后,随机分为A、B、C 3组,A组为感染组,B组为灌胃白藜芦醇治疗组,C组为灌胃吡喹酮治疗组,另取15只正常C57BL/6小鼠为健康对照D组。在感染第13周,取小鼠的肝脏,应用天狼猩红染色观察肝脏纤维化程度,并检测肝脏中IL-13、IFN-γ和TGF-β mRNA的表达情况。另取脾脏淋巴细胞,采用流式细胞术检测Th1和Th2细胞占总T淋巴细胞的比例。结果感染第13周,与A组相比,B组和C组小鼠肝脏纤维化程度明显减轻(P<0.01),B组小鼠的Th1细胞比例明显增高(P<0.05),Th2细胞比例明显降低(P<0.01),B组小鼠外周血清中的抗可溶性成虫抗原(SWA)的IgG2a明显增多(P<0.05),而抗可溶性虫卵抗原(SEA)的IgG1明显减少(P<0.01),B组小鼠肝脏中IFN-γ mRNA的表达量明显增高(P<0.05),而IL-13、TGF-β mRNA的表达水平明显降低(P<0.01)。结论白藜芦醇通过增强日本血吸虫感染小鼠的Th1应答,降低Th2应答,明显抑制日本血吸虫感染小鼠肝脏纤维化程度。

Aim To observe the antifibrogenic effect ofresveratrol on mice with schistosomiasis japonica andits effect on Th1 and Th2 responses. Metliods Fortyfivemice infected with S. japonicum cercariae for 3weeks were randomly divided into three groups namedas infection group （ A ） ,resveratrol group （ B ） and praziquantelgroup （ C ） . Fifteen normal mice were taken asnormal control group （ D ） . In the 13 th week post-infection,all mice were sacrificed and the liver tissues wereremoved. Histopathological changes were observed inthe liver of all groups. Splenocytes were prepared fromspleens of mice with S. japonicum infection and theproportions of T h 1 and Th2 cells in T cells were determinedby FACS respectively. RT-PCR was used to detectthe relative IFN-γ , IL-13 , TG F-β mRNA levels inliver tissue. Results After treatment, the degrees ofliver fibrosis in groups B and C decreased in the 13 thweek post-infection （ P〈0.01） . Compared to groupA ,the proportions of T h 1 cells in group B significantlyincreased （P 〈 0. 05 ） and the proportions of Th2 cellsin group B decreased significantly （ P〈0.01） . Thelevel of anti-SWA IgG 2 a in group B was significantly higher （P〈0.05） , while the anti-SEA IgG1 level ingroup B was lowfe r（P〈0.01） than that in group A .The hepatic expression of IFN-γ mRNA level in groupB was higher than that in group A（P〈0.05） , and IL-13 ,TGF-β mRNA levels in group B were lower than ingroup A （P〈0.01） . Conclusion Resveratrol has an antifibrogenic effect through upregulating Th1 cell responseand downregulating Th2 cell response in miceinfected with Schistosoma japonicurm.