芍药苷对感染血吸虫小鼠肝纤维化的影响

Timing effect of paeoniflorin on liver fibrosis in mice infected with Schistosoma japonicum

目的探讨小鼠感染日本血吸虫后经吡喹酮治疗的不同时期,给予芍药苷对肝组织虫卵肉芽肿和纤维化的影响。方法以日本血吸虫尾蚴感染BALB/c小鼠构建肝纤维化模型,随机分为(Ⅰ)杀虫前给药组、(Ⅱ)杀虫同时给药组及(Ⅲ)杀虫后给药组。除正常组外,杀虫治疗、芍药苷治疗组和对照组小鼠分别于感染后12d、42d和72d给予芍药苷和对照,并于102d、132d和162d处死。检测透明质酸(HA)、Ⅲ型前胶原氨基端肽(PⅢP)、羟脯氨酸(Hyp)、虫卵肉芽肿大小、肝纤维化分级以及胶原Ⅰ的表达。结果在组Ⅰ和组Ⅲ,芍药苷明显降低血清中HA、PⅢP和肝组织中Hyp的含量,减小虫卵结节并降低肝纤维化严重程度分级,降低胶原Ⅰ的表达(P<0.05或P<0.01);在组Ⅱ,大部分指标没有明显差别(P>0.05)。结论芍药苷无论是早期或延后给药,都具有抑制虫卵肉芽肿,减少胶原的生成从而对抗小鼠血吸虫性肝纤维化的作用。

To probe the effect of paeoniflorin on periovular granuloma and liver fibrosis in mice infected with Schistosoma japonicum in different times of infection and the treatment with praziquantel （PZQ）. The models of hepatic fibrosis induced by S. japonicum were established by exposure of BALB/e mice percutaneously through the tail to cereariae of S. japonicum, and mice with treatment were randomly divided into 3 groups： i.e. groups of pre-treatment （Ⅰ）, group of simultaneous treatment （ Ⅱ ） and group of post treatment （Ⅲ）. All groups, except the normal control group, were orally introduced with PZQ. And mice in the paeoniflorin-treated group and control group were separately introduced with paeoniflorin and 0.5% sodium carboxymethycellulose respectively. The treatments in group Ⅰ,Ⅱand Ⅲ were started 30 days before PZQ usage, simultaneously with PZQ or 30days after PZQ usage respectively. Mice in these groups were sacrificed on the 102, 132 or 162 days after infection. Then the serum levels of hyaluronic acid （HA）, amino-terminal peptide of type Ⅲ procollagen （PⅢP） and liver hydroxyproline （Hyp） were detected. The histopathology was examined by HE and Masson staining; the degree of hepatic fibrosis and the area of egg granuloma were analyzed. The expression of collagen I was examined by immunohistochemical method. It was found that the area of granuloma and degree of hepatic fibrosis in the paeoniflorin-treated groups in groupⅠ and Ⅲ were significantly lower than those in the model control groups. Also, paeoniflorin could induce decreas expression of collagen I. Meanwhile the levels of serum HA, PIIIP and liver Hyp were all reduced in comparison with those in the control group （P〈 0.05 or P〈0.01）. However, in group Ⅱ , no significant difference was noted between the treated and the control group in most data. Paeoniflorin also showed the effects to reduce the size of periovular granuloma and to reduce the expression of type I collagen, thereby to resist the development of hepatic fibrosis caused by S. japonicum. It is evident that PAE shows an efficaciously therapeutic effect on the development of liver fibrosis of shistosomiasis, whenever it is administered before or after the usage of schistosomicides.