不同剂量吉非替尼对博莱霉素所致大鼠肺纤维化影响的比较

摘要

Objective To compare the effect of different doses of gefitinib on the extent of fibrosis in rat models of pulmonary fi‐brosis induced by bleomycin (BLM) .Methods Seventy five female rats were randomly assigned to five groups and treated as fol‐lows :the rats in control group were given water orally with administration of saline intratracheally ;the rats in BLM group were giv‐en water orally with a single intratracheal injection of BLM (5 mg/kg body weight in 0 .2 mL phosphate buffered saline);the rats in BLM+Ge20 group was given gefitinib at dose of 20 mg・ kg -1 ・ d-1 orally with administration of bleomycin intratracheally ;the rats in BLM+Ge90 group were given gefitinib at dose of 90 mg・kg -1 ・d-1 orally with administration of BLM intratracheally ;the rats in BLM+Ge200 group were given gefitinib at dose of 200 mg・kg -1 ・d-1 orally with administration of BLM intratracheally . Twenty one days later ,all rats were sacrificed .Left pulmonary lobes from all animals were removed and stained with hematoxylin , eosin and Masson′s trichrome respectively for pathological examination ,and the right pulmonary lobe tissues were used for the hydroxyproline contents measurement (by ELISA ) .Results Gefitinib augumeted rat pulmonary fibrosis induced by bleomycinin with significantly increasing Ashcroft score ,lung collagen accumulation and the level of hydroxyproline (HYP) in BLM + Ge200 group (P<0 .05) .The hydroxyproline content of pulmonary tissue was increased in BLM+Ge90 group conmpared to those in BLM group (P<0 .05) ,while Ashcroft score was not increased .However ,there was no significant difference in the indicators above be‐tween the BLM+Ge20 group and the BLM group (P>0 .05) .Conclusion Gefitinib augumets rat pulmonary fibrosis induced by bleomycin .The bigger the gefitinib dosage is ,the more severe pulmonary fibrosis would be .%目的：对比观察不同剂量吉非替尼对博莱霉素所致大鼠肺纤维化的影响。方法将75只雄性SD大鼠分为5组：对照组、博莱霉素组、低剂量吉非替尼联用组、中剂量吉非替尼联用组、高剂量吉非替尼联用组，每组15只。观察大鼠存活情况，第21天时杀鼠取左肺石蜡切片行HE染色及Masson染色，右肺ELISA方法检测羟脯氨酸含量。结果高剂量吉非替尼联用组能明显加重博莱霉素所致肺纤维化，Ashcroft评分、肺组织胶原沉积及羟脯氨酸含量明显增多（P＜0．05）。中等剂量吉非替尼联用组Ashcroft评分较博莱霉素组差异无统计学意义（P＞0．05），羟脯氨酸含量明显增加（P＜0．05）。而低剂量吉非替尼联用组各项指标与博莱霉素组比较，差异无统计学意义（P＞0．05）。结论吉非替尼能加重博莱霉素所致大鼠肺纤维化，且吉非替尼剂量越大，大鼠肺纤维化程度越高。