芍药苷对日本血吸虫病肝纤维化小鼠CTGF PDGF及TNF-α的影响  

Effects of paeoniflorin on expressions of CTGF, PDGF and TNF-α in mice with hepatic fibrosis due to Schistosoma japonicum infection

作　　者：肖晖[1] 魏恒[1] 杨光斌[2] 彭惠玲[2] 张聪[2] 

机构地区：[1]武汉大学中南医院血液内科,武汉430071 [2]湖北省疾病预防控制中心血吸虫病防治研究所

出　　处：《中国血吸虫病防治杂志》2011年第3期288-291,F0003,共5页Chinese Journal of Schistosomiasis Control

基　　金：湖北省卫生厅血防科研专项基金(XF2008-17)

摘　　要：目的观察芍药苷对日本血吸虫感染小鼠肝脏结缔组织生长因子(CTGF)、血小板衍化生长因子(PDGF)蛋白表达水平和血清中肿瘤坏死因子α(TNF-α)水平的影响,探讨芍药苷预防血吸虫病肝虫卵肉芽肿及纤维化的作用机制。方法小鼠随机分为A～E5组,A组不感染血吸虫尾蚴,为正常对照组;B、C、D、E4组小鼠感染尾蚴后6周以吡喹酮灌胃杀虫,剂量为400mg/(kg·d),连续2d。B、C、D3组杀虫后给予芍药苷,剂量分别为30、60、120mg/(kg·d)),E组不给芍药苷,为感染对照组。5组小鼠均在芍药苷给药8周后处死,取血及肝脏。HE及Masson胶原纤维染色观察肝虫卵肉芽肿面积及纤维化程度,采用免疫组化技术检测CTGF和PDGF蛋白表达情况,采用ELISA法检测小鼠血清中TNF-α水平。结果芍药苷高剂量的D组与感染对照E组相比,肝组织中CTGF和PDGF蛋白表达明显减少,血清中TNF-α水平也明显下降(P均<0.05);而中、低剂量B组和C组的CTGF、PDGF和TNF-α水平亦较E组减少,但差异无统计学意义(P均>0.05)。结论芍药苷抗血吸虫病肝纤维化作用呈剂量依赖性,在吡喹酮杀虫处理基础上联合应用高剂量芍药苷,可通过减少肝组织CTGF和PDGF蛋白表达,降低血清中TNF-α水平,减轻肝纤维化程度。Objective To observe the effects of paeoniflorin on the expressions of CTGF and PDGF in liver tissue of fibrosis and the serum level of TNF-α in mice infected with Schistosoma japonicum, and to explore the protective effect and its mechanisms of paeoniflorin on 1iver fibrosis. Methods Kunming mice were divided randomly into 5 groups, namely normal control group （Group A）, paeoniflorin groups （Group B, C, D） and infected control group （Group E）. The mice in Group B-E were infected with cercariae of Schistosoma japonicum, and then they were treated with praziquantel （400 mg/kg per day） for 2 days after 6 weeks. After that, the mice in Group B, C, D were given paeoniflorin with a dose of 30, 60, 120 mg/ （kg·d）, respectively. After 8 weeks of paeoniflorin treatment, all the mice were killed, and their livers and serum were obtained. Hematoxylin and eosin stain and Masson stain were used to observe the degree of hepatic fibrosis. Immunohistochemical staining was performed to detect the expressions of CTGF and PDGF in liver tissue. The serum level of TNF-α was detected by ELISA. Results The expression levels of CTGF and PDGF proteins in liver tissue and the serum level of TNF-α of the mice in the high dosage paeoniflorin treatment group （Group D） were significantly lower than those in the infected control group （P〈0.05）. Conclusions The effects of paeoniflorin on hepatic fibrosis induced by Schistosoma japonicum infection depends on its dosage. Paeoniflorin may exert its effects by inhibiting the serum level of TNF-α and down regulating the expression of CTGF and PDGF proteins.

关 键 词：日本血吸虫 芍药苷 肝纤维化 结缔组织生长因子 血小板衍化生长因子 肿瘤坏死因子α 

分 类 号：R383.24[医药卫生—医学寄生虫学]