缺氧诱导因子-1α与百草枯中毒致急性肺损伤早期肺纤维化的关系  

The relationship between HIF-1α expression and the early lung fibrosis in rats with acute paraquat poisoning

作　　者：王瑞兰[1] 唐雪[1] 吴欣[1] 徐榕[1] 俞康龙[1] 徐侃[1] 

机构地区：[1]上海交通大学附属上海市第一人民医院危重病科,201620

出　　处：《中华劳动卫生职业病杂志》2012年第4期273-277,共5页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：上海市科委资助项目（08411962800）

摘　　要：目的探讨缺氧诱导因子-1α（HIF-1α）在百草枯（PQ）中毒大鼠肺组织急性肺损伤早期肺纤维化中的作用。方法将48只健康SD大鼠随机分为对照组（6只）和PQ染毒组（42只）。对照组大鼠予生理盐水1ml，一次性灌胃；将质量分数为20％的PQ用生理盐水稀释，对染毒组大鼠一次性灌胃染毒1ml（500mg／kg），按灌胃后2、6、12、24、48、72及120h分为7个亚组，每组6只。分别测定各组大鼠的动脉血氧分压（PaO2）；进行肺组织HE染色、Mason染色，观察病理学变化；肺组织荧光染色观察肺组织变化及HIF1-1α蛋白表达；用免疫蛋白印迹（Westernblot）法检测HIF-1α蛋白表达。结果染毒72h组大鼠动脉血PaO2为（62．33±0．22）mmHg，与对照组[（96．00±5．20）mmHg]比较，差异有统计学意义（P〈0．05）。HE染色可见，染毒后2h大鼠肺泡毛细血管内皮细胞、肺泡上皮细胞和肺间质的急性弥漫性损害，广泛肺间质炎性细胞浸润，增厚；染毒后12h肺间质水肿减轻，肺泡间距变窄；染毒后120h，肺泡结构紊乱，较多量片状分布瘢痕条索，成纤维细胞明显增多，外周炎症吸收。Masson染色可见，染毒后2h大鼠肺泡上皮出现明显胶原沉积；24、48h蓝染的胶原纤维逐渐增加；染毒后120h肺泡组织明显破坏，大片纤维结缔组织沉积。免疫荧光及Westernblot法均显示，染毒组大鼠染毒后2h肺组织中HIF1-a蛋白表达明显升高，至12h达峰值，24、48h逐渐下降，但仍高于对照组，染毒组各时间点HIF-1α蛋白表达与对照组的差异有统计学意义（P〈0．05）。染毒组各时间点HIF-1α蛋白表达比较，差异无统计学意义（P〉0．05）。结论PO中毒大鼠肺组织早期即出现肺纤维化及HIF-1α蛋白的表达，HIF-1α可能参与了肺纤维化的形成。Objective To explore the role of hypoxia-inducible factor 1 alpha （HIF-lct） in early lung fibrosis of rats with acute paraquat （PQ） poisoning. Methods Forty eight healthy SD rats were randomly divided into control group （6 rats） and paraquat poisoning group （42 rats）. Control group was exposed to 1 ml normal solution by gastric gavage. The paraquat group was exposed to 1 ml paraquat solution （50 mg/kg） by gastric garage for 2, 6, 12, 48, 72 and 120 h, respectively. The arterial blood gas analysis （PaO2） was detected. The pathologica! examinations of lung tissues were performed by HE and Mason staining. HIF-1α in lung tissues were measured by immunofluorescence. Western blot assay was used to detect the expression levels of HIF-1α protein in lung tissues. Results PaO2 of rats exposed to paraquat for 72 h was （62.33±0.22） mm Hg, which was significantly lower than that （96.00±5.20） of control group （P〈0.05）. Pathological examination by HE staining indicated that the acute diffuse lesion appeared in the lveolar capillary endothelium, epithelia and interstitial tissues, and there was the inflammatory cell infiltration in the alveolar of rats exposed to paraquat at 2 h after exposure. At 12 h after exposure, the interstitial edema in lung tissues of rats decreased and the lveolar space became narrow. At 120 h after exposure, there were the alveolar structure derangement, abundant cicatrix, more fibroblasts and peripheral inflammation absorption. Pathological examination by Masson staining showed that there was obvious collagen deposition in the lveolar epithelia at 2h after exposure, the increased collagen fibrosis at 24 and 48 h after exposure and the obvious damage of alveolar tissues or much more fibrous connective tissue deposition at 120 h after exposure. The results of western blot and immunolfluorence assays exhibited that the expression levels of HIF-1α in lung tissues at 2, 24 and 48 h after exposure significantly increased, as compared with control group （P〈0.05�

关 键 词：百草枯 中毒 缺氧诱导因子-1Α 肺纤维化 

分 类 号：R595.4[医药卫生—内科学]