视黄酸调节Smad3表达阻抑放射诱导的肺损伤

为了探讨信号蛋白Smad3于不同时间段,在放射性肺损伤大鼠肺组织中的表达变化,以及视黄酸对其表达的影响,以6MV-X线对健康雄性Wistar大鼠进行15Gy全胸野照射,建立大鼠放射性肺损伤模型,并用视黄酸进行干预。实验分为正常对照组(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)。于照射后第1、2、4、8周后取肺组织作HE和Masson染色、并以免疫组化方法检测Smad3。结果表明,照射后1周,发现肺泡腔有炎性细胞渗出,继而间质水肿,4及8周出现肺泡腔变小、结构破坏,肺间质出现胶原纤维;B组与A组比,各时间段的病理无明显差别,但D组与C组相比,大鼠肺炎和肺水肿减轻,肺组织胶原纤维量减少。Smad3免疫组化学标记显示:A组与B组相比,检测的4个时间点均无差别;C组和D组与A组比,在放疗后的第1、2、4、8周时间段Smad3表达均明显增强(p0.0001),以C组增强更明显;D组与C组比,Smad3表达减弱,以第4、8周表达减弱更明显。由此可见,放射性肺损伤肺组织Smad3表达明显增强,视黄酸对大鼠正常肺组织的Smad3表达无影响,但它能从蛋白质水平上有效抑制放射诱导的Smad3表达,对放射性肺损伤有防治作用,为临床用其治疗放射性肺损伤提供了实验依据。

Study on the accommodation of Smad3 expression and restraint of lung injury induced by radiation by use of retinoic acid

In order to investigate the effect of retinoic acid (RA) on the pathology and Smad3 expression in the pulmonary injury induced by radiation, wistar rats were irradiated with 6MV-X rays linear accelaretor at dose of 15Gy and RA was used as interfering agent by setting control group(group A), treatment group(group B), radiation group(group C) and radiation with RA treatment group(group D). In 1, 2, 4, 8 weeks after irradiation, HE staining and Massion staining were used to detect the pathological change of pulmonary tissues while immunohisto-chemistry staining was used to measure the expression of Smad3 level. The study shows that inflammatory cells exudation occurs in alveolar spaces at one week after irradiation then followed by interstitial edema, shrinkage and destroying of structure. The local consol and collagen fibers appear in pulmonary interstitial at 4 and 8 weeks after irradiation. No significant difference of pathology has been observed between the simple treatment group and the control grup, but obviously decrement has been observed in group C and group D. The expression of Smad3 has been enhanced significantly in group C and group D at 1, 2, 4, 8 weeks(p＜0.00001)after irradiation compared with that of group A while it is weakened in group D compared with group C, especially at 4, 8 weeks after irradiation. However, no statistical difference has been found between group A and group B. Accordingly, Smad3 does participate in the process of radiation induced lung injury while RA restrains the expression of Smad3 in protein level. And it may provide a useful evaluation to curing of radiation- induced lung injury.