人参皂苷Rg3抗血吸虫病肝纤维化作用的实验研究

Effect of Ginsenoside Rg3 on Hepatic Fibrosis in Murine Schistosomiasis Japonica

目的观察人参皂苷Rg3抗日本血吸虫病肝纤维化的作用和疗效。方法 54只雄性IcR小鼠随机分为健康对照组（A组）、感染对照组（B组）、吡喹酮加人参皂苷Rg3治疗组（C组）和吡喹酮治疗组（D组）等4组,A组18只,其余每组12只。日本血吸虫尾蚴以腹部贴片法经皮肤攻击感染B、C和D组小鼠,每鼠感染尾蚴18-22条。感染后10周,称取各小鼠体重,A、B组小鼠分别取左叶肝组织,于10%甲醛溶液中固定,保存备用。C、D组每鼠吡喹酮一次性灌胃（300 mg/kg）杀虫治疗。吡喹酮治疗次日起,C组每鼠予以人参皂苷Rg3 3 mg/（kg.d）灌胃治疗,连续8周。治疗8周后,处死所有剩余小鼠,在每鼠的左叶肝组织于相同部位取材,石蜡包埋,连续切片（厚度为4μm）,进行苏木素-伊红（HE）染色和苦味酸-酸性品红（VG）染色,观察肝组织病理学变化和肝脏内胶原沉积情况。参考《慢性肝炎肝纤维化半定量记分（SSS）方案》,对小鼠肝脏纤维化病变程度进行评分并作统计学分析,以评定人参皂苷Rg3的治疗效果。结果 B组小鼠HE染色发现,肝小叶内和汇管区均可见大量虫卵沉积,有嗜酸性脓肿和假结核结节形成,并以汇管区为重;VG染色发现,肝汇管区和虫卵肉芽肿周围可见明显纤维增生,增生的纤维组织主要沿汇管区分布,形成干线型纤维化,部分纤维呈条索状,向小叶内延伸,形成纤维间隔。C组小鼠经人参皂苷Rg3治疗8周后,肝脏仍有不同程度增大,呈暗褐色,质地略韧;肝脏内纤维增生、炎细胞浸润等病变较B组为轻。C组小鼠肝脏胶原面积百分比为（2.32±0.99）%,低于B组[（11.08±4.43）%]和D组[（11.19±4.91）%]（均P〈0.05）。C组小鼠SSS评分（2.83±1.09）显著低于B组（7.42±1.16）和D组（8.08±1.76）（均P〈0.05）。结论吡喹酮治疗后,人参皂苷Rg3具有改善小鼠日本血吸虫病肝纤维化作用。

Objective To investigate the therapeutic efficacy of ginsenoside Rg3 on hepatic fibrosis in murine schistosomiasis japonica.Methods 54 ICR-strain male mice were divided into 4 groups named as normal control group（A）,infected control group（B）,praziquantel＋Rg3 treated group（C） and praziquantel treated group（D）.There were 12 mice in each group,but 18 in group A.Mice in groups B,C,and D were infected with 20±2 cercariae of Schistosoma japonicum.At ten weeks post-infection,10 mice of group A and 12 mice of group B were weighed and sacrificed.Specimens from left hepatic lobes were taken and fixed in 10% formaldehyde solution.Mice in groups C and D were treated intragastrically with praziquantel at a single dose of 300 mg/kg.At the second day after praziquantel treatment,each mouse in group C was given 3 mg/（kg·d） ginsenoside Rg3 for 8 weeks.The rest mice were sacrificed on 8 weeks after treatment,and liver tissue samples from left hepatic lobes were prepared.The histological changes and collagen fiber deposition in the liver tissue sections were observed with hematoxylin-eosin staining and van gieson staining.Liver fibrosis was graded according to semi-quantitative scoring system（SSS） method.Results In group B,many eggs deposited in the hepatic lobules and portal areas,and eosinophilic abscesses and pseudo-tubercles developed in the liver,especially common in portal areas.There were many fibre hyperplasia and deposit inside abbacy and liver flocculus.Pipestem fibrosis formed around the portal areas,and some cord-like fibres extended into hepatic lobules,and formed in the fibrous septa.After 8-week treatment with ginsenoside Rg3,in group C,the livers were initially enlarged,firm and dust-color;and the degree of hepatomegly varied from mild to marked;but the degree of fibre hyperplasia and inflammatory infiltration were mitigated compared with that of group B.Mean percentage of collagen area in group C[（2.32±0.99）%] was lower than that of groups B [（11.08±4.43）%] and D [（11.19±4.91）%]（P0.05）.The SSS scores of hepatic fibrosis in group C（2.83±1.09） was lower than that of groups B（7.42±1.16） and D（8.08±1.76）（P0.05）.Conclusion Ginsenoside Rg3 shows anti-hepatofibrosis effects in murine schistosomiasis japonica after praziquantel treatment.