目的 观察NADPH氧化酶抑制剂二甲苯基碘(DPI)对放射性肺损伤的防治作用,探讨其可能机制.方法 48只成年雄性SD大鼠按随机数字表法分为空白对照组(C组)、单纯照射组(R组)、照射+二甲苯基碘组(R+D组)和单用二甲苯基碘组(D组),每组12只.采用6MVX射线照射双肺,每只每天照射8 Gy,连续照射5d,总剂量40 Gy.R+D组大鼠在每次照射前1h皮下注射0.02% DPI溶液(1 mg/kg);D组大鼠不接受射线照射,只注射DPI溶液.两组大鼠DPI注射从照射前3d开始,持续至照射后30 d.C组和R组大鼠则注射等体积的生理盐水.照射后1个月和6个月时提取肺组织,行HE染色、Masson染色、羟脯氨酸含量测定和TGF-β1免疫组织化学染色.结果 在照射后1个月时,R组出现典型肺泡炎表现,羟脯氨酸含量为(0.69±0.05) μg/mg,TGF-β1阳性染色面积比为(39.97±0.90)%,R+D组羟脯氨酸含量为(0.55±0.03) μg/mg,TGF-β1阳性染色面积比为(33.83±1.55)%,肺泡炎程度轻于R组(t =5.32、5.93,P<0.05).6个月时R组出现典型肺纤维化表现,羟脯氨酸含量为(1.04±0.02) μg/mg,TGF-β1阳性染色面积比为(37.80±0.85)%,R+D组羟脯氨酸含量为(0.85±0.02) μg/mg,TGF-β1阳性染色面积比为(23.93±1.16)%,肺纤维化程度轻于R组(t=15.77、16.68,P<0.05).C组和D组则未发生明显异常变化.结论 二甲苯基碘可以减少大鼠肺部照射后羟脯氨酸及TGF-β1的含量,减轻肺损伤的程度,对放射性肺损伤具有一定的防治作用
Objective To investigate the mechanism of an inhibitor of NADPH oxidases, diphenylene iodonium ( DPI), in preventing radiation-induced lung injury. Methods Totally 48 adult SD male rats were randomly classified into 4 groups: control group (C) , radiation group (R) , radiation plus DPI group (R ± D) and DPI group (D). The radiation induced pulmonary injury model was preformed by using 6 MV X-rays to deliver 8 Gy per day for 5 consecutive days with 40 Gy in total to the thorax of each animal, Rats in R ± D group were subcutaneously administered with 0. 02% DPI ( 1 mg/kg) at 1 h prior to radiation while rats in D group received the same dose of DPI without radiation. DPI was given from 3 d before radiation to 30 d after the first radiation. Rats in C and D groups received the same dose of saline. Animals were sacrificed at 1 month and 6 months after radiation, respectively. The lungs were removed and processed for HE and Masson staining, hydroxyproline content measurement, and TGF-131 immunohistochemical detection. Results At 1 month post-radiation, rats in R group showed typical alveolitis, the level of hydroxyproline was (0.69 ± 0. 05 ) μg/mg, and the positive area of TGF-β1 expression was (39.97 ± 0.90) % , while the level of hydroxyproline in R ± D group was (0. 55 ± 0. 03 ) Ixg/mg and the positive area of TGF±[31 expression was(33.83 ± 1.55)% , rats in R ± D group showed less severe alveolitis compared with R group( t =5.32,5.93 ,P 〈0.05). At 6 months post-radiation, rats in R group showed typical lung fibrosis with hydroxyproline level of ( 1.04 ± 0.02 ) tzg/mg and TGF-[31expression of (37.80 ± 0.85 ) % , whereas the hydroxyproline level in R ± D group was (0.85 ± 0. 02) p.g/ rag, the TGF-β1 expression was(23.93 ± 1. 16) % , rats in R ± D group showed moderate lung fibrosis( t = 15.77,16.68,P 〈 0. 05 ) , rats in C and D group had no noticeable changes. Conclusions Diphenylene iodonium could prevent radiation-induced lung i