维甲酸及氟伐他汀对放射性肺损伤防治作用的实验研究

Effects of retinoic acid and fluvastatin on radiation-induced lung injury

目的:观察维甲酸(RA)和氟伐他汀(Flu)对放射性肺损伤的防治作用。方法:雌性SD大鼠80只随机分为正常对照组、单纯照射组、治疗组和预防组。后3组麻醉后,行直线加速器全胸部照射。预防组于照射前7 d以RA、Flu各10 mg/(kg.d)灌胃;治疗组于照射后次日灌服RA、Flu各10 mg/(kg.d);另两组灌服等量生理盐水直至实验结束。分别于照射后5、15、30和60 d每组各取5只大鼠,观察肺组织标本HE染色和胶原纤维染色;肺组织TGFβ-1免疫组化检测以计算机图像分析系统测定。结果:治疗组和预防组大鼠肺炎和肺水肿比单纯照射组明显减轻,胶原纤维含量也明显减少。单照组在照射后5、15、30和60 d肺组织TGFβ-1阳性面积与正常对照组比较逐渐增大,P<0.01;而治疗组和预防组与同期单照组比较明显减小,P<0.05;预防组在15和30 d与同期治疗组比较明显减小,P<0.01。结论:RA联合Flu能有效地减轻放射性肺炎,抑制胶原纤维增生。预防组较治疗组能更好地减轻放射性肺损伤。

OBJECTIVE： To observe the effects of retinoic acid （RA）and fluvastatin（Flu） on radiation induced lung injury. METHODS： Eighty female SD rats were divided into 4 groups： a normal control （Group C）, radiated group （Group R）, treatment group（Group T） and prevention group （Group P）. The latter 3 groups were radiated with linear accelerator after anesthesia. RA together with Flu was given to the rats in Group T at a dose of 10 mg/（kg · d） by gastrogavaging from 7 days before radiation until the end of the experiment. The day after the radiation, RA together with Flu was gastrogavaged at a dose of 10 mg/（kg · d） in Group P. The rats in other groups were gastrogaraged with the same amount of saline. Five rats of each group were sacrificed respectively on 5,15, 30 and 60 days. Hematoxylin and eosin （HE） stain and Van Gieson stain were performed on the lung tissue slices to observe the changes in microstructure. The expression of TGF-β1 was measured by immunohistochemistry staining. RESULTS： Pneumonia and pulmonary edema in rats of the treatment group and prevention group were much less severe than those in rats of the radiation group. The amount of collagen fibers in lung tissue from rats of the radiation group increased significantly compared with the treatment group. TGF-β1 positive areas of lung tissue increased in Group R 5,15,30 and 60 days after radiotherapy compared with Group C, P〈0.01, while decreased significantly in Group T and P（P〈0.05）, and decreased in Group P on 15 and 30 days compared with Group T, P〈0.01. CONCLUSION： RA together with Flu may alleviate radiation induced pneumonia and inhibit the proliferation of collagenous fibers,which is more effective in the prevention group compared with the treatment group.