当归注射液及前列腺素E_2对结缔组织生长因子在大鼠肺纤维化模型中表达作用的比较研究

目的探讨结缔组织生长因子(CTGF)在大鼠肺间质纤维化中的表达及其在25%当归注射液、前列腺素E2(dmPGE2)的肺脏保护作用中的意义。方法SD大鼠随机分为对照组、模型组、当归组、PGE2组。按博莱霉素(BLM)5mg/kg体重复制大鼠肺纤维化模型,当归组、dmPGE2组术后分别给于25%当归注射液(腹腔内注射)、dmPGE2(肌肉注射),于第28天处死全部大鼠。制备大鼠肺组织切片,用原位杂交及免疫组化SABC法分别检测CTGF mRNA、纤维连结蛋白(FN)和Ⅲ型胶原(Col-Ⅲ)在肺内的表达,HE染色评价肺纤维化程度。结果模型组CTGF mRNA、FN和Col-Ⅲ的表达及肺纤维化程度明显高于对照组(P<0.01),而当归组及PGE2组明显低于模型组(P<0.01)。两治疗组间比较,除CTGF外,其余指标无显著性差异(P>0.05),各组指标的相关分析表明,CTGF表达水平与肺纤维化程度(r=0.886;P<0.01)、FN(r=0.836;P<0.01)和Col-Ⅲ(r=0.918;P<0.01)呈正相关关系。结论25%当归注射液可能通过下调CTGF而减轻肺间质纤维化。

Comparative Effect between Angelica Sinensis and Prostaglandin E_2 on Expression of Connective Tissue Growth Factor in Rats with Pulmonary Fibrosis Induced by Bloemycin Treatment

Objective: To investigate the expression of CTGF mRNA in rats with pulmonary fibrosis induced by bloemycin treatment and the effects of prostaglandin E_2(dmPGE_2) and angelica sinensis(A&S)treatment on expression of CTGF mRNA. Method: Of 84 male Sprague-Dawley rats ,21 rats were randomly selected as normal control group,and were intratracheally instilled with sterile saline(5 mg/kg body weight);the others were intratracheally instilled with bleomycin(5 mg/kg body weight),and then were randomly divided into 3 groups: model group, dmPGE_2 group (were given dmPGE_2 1nmol/kg·d intramuscular injection after given bleomycin), A&S group (were given A&S 10 ml/kg·d abdominal cavity injection after given bleomycin). On day 28 after instillation,all rats of each group were sacrificed and the lung tissues were harvested for histopathological examination.The expression of CTGF mRNA, fibronectin(FN) and collagen-Ⅲ were measured by using in situ hybridization and SABC immunohistochemical technique. At the same time,the degree of pulmonary fibrosis was scored.Results: The levels of CTGF mRNA,FN and collagen-Ⅲ protein in the model group increased remarkably comparing with the control group(P<0.01)and paralleled with the degree of pulmonary fibrosis.In comparison with the model group,the levels of CTGF mRNA,and expression of FN and collagen-Ⅲ were siginficantly reduced by both dmPGE_2 and A&S treatment.The expression level of CTGF mRNA had positive correlation with the degree of pulmonary fibrosis(r=0.886;P<0.01),FN(r=0.836;P<0.01) and collagen-Ⅲ(r=0.918;P<0.01).Conclusion: dmPGE_2 and A&S may suppress pulmonary fibrosis development,at least in part via down-regulating CTGF mRNA expression.