肺纤维化模型大鼠肺组织中转化生长因子β1及转化生长因子β1mRNA的表达及黄芪莪术合剂的干预效应

Interventional effect of huangqi ezhu heji on the expression of transforming growth factor-beta 1 and transforming growth factor-beta 1 mRNA in the lung tissues of rats with pulmonary fibrosis

目的:分析中药黄芪莪术合剂对博莱霉素所致大鼠肺间质纤维化的干预作用。方法:实验于2002-10/2003-02在天津中医药大学动物实验室完成。①健康SD大白鼠60只,正常饲养1周后,随机分为正常对照组6只、模型组18只、黄芪莪术合剂组18只、强的松组18只。②经气管滴入博莱霉素复制肺纤维化大鼠模型,黄芪莪术合剂组给予40.5mg/L黄芪莪术合剂,强的松组给予0.63g/L强的松盐水溶液,均采用灌胃方式给药,每次1.5mL,1次/d。正常对照组、模型组给予等量生理盐水。③模型组、黄芪莪术合剂组、强的松组分别于造模第3,7,21天每组6只麻醉下取右肺下叶组织后处死,正常对照组于第3天麻醉下取右肺下叶组织后处死。④采用免疫组织化学方法和原位杂交方法检测肺组织转化生长因子β1及转化生长因子β1mRNA的表达。结果:进入结果分析大鼠55只,中途脱落5只。①转化生长因子β1表达:造模第3,7,21天模型组高于正常对照组(P<0.01),黄芪莪术合剂组和强的松组明显低于模型组(P<0.01～0.05)。造模第3,21天强的松治疗组低于黄芪莪术合剂治疗组(P<0.05)。②转化生长因子β1mRNA表达:造模第3,7,21天模型组高于正常对照组,黄芪莪术合剂组和强的松组明显低于模型组(P<0.01);第7天时,强的松治疗组低于黄芪莪术合剂治疗组,第21天时黄芪莪术合剂治疗组低于强的松治疗组,差异均有显著性意义(P<0.05)。结论:中药黄芪莪术合剂具有显著抑制博莱霉素致大鼠肺纤维化的作用,抑制转化生长因子β1及转化生长因子β1mRNA的表达是其可能的机制之一。

AIM：To investigate the intervention of Chinese herb huangqi ezhu heji （QZHJ, astragali and curcumae） on bleomycin-induced pulmonary fibrosis in rats. METHODS： The experiment was conducted in the animal laboratory of Tianjin University of Traditional Chinese Medicine between October 2002 and February 2003. ①After feed for one week, sixty healthy SD rats were randomly divided into normal control group （n =6）, model group （n =18）, QZHJ treated group （n =18）, and dehydrocortisone treated group （n =18）. ②The rat models of pulmonary fibrosis were established by transtracheal instillation of bleomycin; the QZHJ group was given 40.5 mg/L QZHJ; the dehydrocortisone treated group was given 0.63 g/L dehydrocortisone solution, 1.5 mL every time, once daily; the control group and model group were given matching normal saline. ③Six rats of the model group, QZHJ group and dehydrocortisone treated group were sacrificed after the removal of inferior lobe of right lung under anesthesia on the 3^rd, 7^th and 21^st days, and the rats in the control group were sacrificed on the 3^rd day. ④ Transforming growth factor-β1 （TGF-β1） and TGF-β1 mRNA expressions in lung tissues were detected by immunohistochemistry and in situ hybridization methods. RESULTS： Totally 55 rats were involved in the result analysis with 5 lost in midway. ①Expressions of TGF-β1 ： On days 3, 7 and 21 after modeling, the TGF-β1 expression in the model group was higher than the normal control group （P 〈 0.01）, QZHJ treated group and dehydrocortisone treated group were significantly lower than the model group （P 〈 0.01- 0.05）. On days 3 and 21, the expression of the dehydrocortisone treated group was lower than the QZHJ treated group （P 〈 0.05）. ②TGF-β1 mRNA expression： On days 3, 7 and 21 after modeling, the TGF-β1 mRNA expression in the model group was higher than the normal control group, and the QZHJ treated group and dehydrocortisone treated group were significantly lower than the model group （P 〈 0.01）; on day 7, the dehydrocortisone treated group was lower than the QZHJ treated group, but on day 21, the QZHJ group was lower than the dehydrocortisone treated group, which had significant differences （P 〈 0.05）. CONCLUSION： Chinese herb has a notable inhibitory effect on the bleomycin induced pulmonary fibrosis in rats, which may be related with the inhibition of TGF-β1 and TGF-β1 mRNA expression.