视黄酸调节EGFR和SP-A表达阻抑放射诱导肺损伤的探讨

Prevention of radiation induced lung injury by retinoic acid through regulating expressions of epidermal growth factor receptor and pulmonary surfatcant-associated protein A

目的:探讨视黄酸(RA)对放射性肺损伤模型大鼠支气管肺泡灌洗液(BALF)细胞数和EGFR及肺泡表面活性蛋白A(SP-A)表达的影响。方法:80只Wister大鼠随机分为正常对照组(A组)、单纯给药组(B组)、单纯照射组(C组)和照射加给药组(D组),C、D组大鼠行6MVX射线15Gy全胸野照射,B、D组给予20mg/(kg·d)RA制剂灌服,于照射后第1、2、4和8周行支气管肺泡灌洗及留取肺组织行HE、Masson染色及免疫组化法检测EGFR表达,蛋白质印迹法检测肺组织中SP-A蛋白表达。结果:放射组大鼠全胸单次15Gy照射后可以建立急性放射性肺损伤动物模型。与D组相比,C组BALF总数升高,肺内炎性渗出增多,胶原纤维增加,EGFR表达增强,以第4、8周最显著(P<0.01),C组各时间段SP-A蛋白表达均明显下降(P<0.001),以第1、8周最明显,第2、4周出现回升。B与C组各时间段相比SP-A蛋白表达差异无统计学意义。D组SP-A蛋白表达与C组比第1、8周差异无统计学意义,第2、4周均高于照射组(P<0.05),但仍低于正常组。结论:RA通过降低炎性细胞渗出,削弱EGFR和促进SP-A表达,预防放射性肺损伤的发生、发展。

OBJECTIVE：To investigate the effect of retinoic acid （RA） on the cell quantity in bronchoalveolar lavage fluid （BALF）,and the expressions of EGFR and the pulmonary surfactant-associated protein A（SP-A） by establishing a model of radiation induced lung injury of rats. METHODS：Eighty Wistar rats were randomly divided into four groups with twenty rats in each group：a control group （A）,drug administration group （B）,radiation group （C）,radiation plus drug administration group （D）. Group C and D were radiated with 6 MV X ray at the dose of 15 Gy to the whole chest. Group B and D were given with RA by gastrogavage at the dose of 20 mg/（kg·d）. The bronchoalveolar lavage and lung tissues were obtained at the 1st,2nd,4th,8th week after the radiation respectively. The lung tissues were used to detecting the expression of EGFR through the HE and Massion stain and immunohistochemistry,and the expression of the pulmonary SP-A through the Western blot method. RESULTS：The acute radiation induced lung injury model was established by 15 Gy 6 MV X ray radiating to the whole chest. The cell quantity of BALF and the pulmonary inflammatory exudates increased,and the expression of EGFR enhanced in the radiation group comparing to the radiation plus drug administration group,which were obviously at the 4th and 8th week （P〈0.01）. The expression of SP-A protein in Group C was remarkable decreased in all the periods （P〈0.001）,especially at the 1st,8th week while increased back again at the 2nd and 4th week. There was not obvious difference in the expression of SP-A protein between Group B and Group C. The expression of SP-A protein in Group D did not show difference with Group C in the 1st and 8st week,while it became higher than that in the radiation group （P〈0.05） but lower than that in the hormal group at the 2nd and 4th week. CONCLUSION：RA prevents the occurrence and development of radiation induced lung injury through reducing inflammatory cells leakage,reducing the expression of EGFR and promoting the expression of SP-A protein.