TGF-β介导盆腔淋巴管放射性纤维化作用机制的研究

TGF-β-Mediated Radiation Fibrosis after Introoperative Radiotherapy in Pelvic Vascellum Lymphaticum

目的:探讨转化生长因子-β(TGF-β)介导盆腔淋巴管放射性纤维化作用的机制。方法:20只雌性新西兰大白兔随机分成空白对照组(Sham组)、照射后4周组、照射后12周组和照射后16周组。除Sham组外,其余各组大白兔均给予放射线单次、大剂量照射。实验第4周、第12周和第16周末用水合氯醛麻醉各组大白兔,解剖,取盆腔淋巴管,染色光镜下分别观察盆腔淋巴管组织病理变化。提取盆腔淋巴管组织,采用蛋白印迹法检测TGF-β、缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)的表达变化。结果:Sham组大白兔盆腔淋巴管组织中细胞排列整齐,无炎性细胞浸润;照射后4周可见少量炎性细胞浸润和水肿;照射后12周可见红细胞和巨噬细胞聚集,大量炎性细胞浸润、水肿显著;照射后16周可见管壁增厚、炎性细胞浸润明显,胶原增生明显。Azan染色Sham组盆腔淋巴管组织中未见纤维化表达,照射后4周大白兔盆腔淋巴管组织中少见蓝色纤维化表达,照射后12周和16周直肠组织中可见大量纤维化表达。盆腔淋巴管组织中TGF-β蛋白表达随照射后时间的延长表达增加,核内HIF-1α蛋白以及细胞浆内VEGF蛋白表达也随照射后时间的延长表达增加。结论:照射增加TGF-β蛋白表达可能与HIF-1α和VEGF蛋白相关,TGF-β可能通过影响HIF-1α从而调控盆腔淋巴管放射性纤维化。

Objective.To investigate the mechanism of radiation fibrosis after introoperative radiotherapy in pel- vic vascellum lymphaticum. Methods.20 big female New Zealand albino rabbits were randomly assigned into con- trol group,4-week irradiation group ,12-week irradiation group, and 16-week irradiation group. All rabbits were an- esthetized with chloralization after 4th 12th and 16th, and dissected. Rectum were collected and pathological changes were observed under light microscope. Proteins of rectum were extracted,and expressions of TGF-β , HIF-la and VEGF were detected by western blot. Results= In rectum tissue sections of control group, cell ar- ranged in order without inflammatory cell infiltration. In 4-week irradiation group, small amounts of inflammatory cell infiltration, congestion and edema were observed. In 12-week irradiation group, magnanimous inflammatory cell in- filtration and significant congestion and edema were observed. In 16-week irradiation group,there were macro- phage,inflammatory cell infiltration and magnanimous fibrosis. With azan staining,there was no fibrosis in control group,less blue fibrosis in 4-week irradiation group,and magnanimous blue fibrosis in 12-week and 16-week irra- diation group. Expressions of TGF-β , HI F-la and VEGF increased with exposure time. Conclusions. Irradiation could increase expression of TGF-β via HIF-la and VEGF to regulate radiation fibrosis in pelvic vascellum lym- phaticum.