性激素对百草枯中毒所致急性肺损伤及肺纤维化保护作用的病理学研究

目的 探讨性激素(雌激素、抗雄激素)对大鼠百草枯(PQ)中毒所致急性肺损伤及肺纤维化的治疗作用及可能的机制.方法 SD雄性大鼠144只,随机分成6组,每组24只:正常对照组(A组)、染毒对照组(B组)、酒精对照组(C组)、雌激素(2.0 mg/kg)治疗组(D组)、抗雄激素(1.0 mg/kg)治疗组(E组)、雌激素+抗雄激素治疗组(F组)；以腹腔注射PQ制作大鼠PQ中毒肺损伤模型,动态观察各组大鼠行为学变化,于染毒后第3、6、15、24天分别予各组大鼠行胸部CT扫描进行影像学观察.实验结束后处死动物,取肺组织行HE染色、Masson染色、免疫组织化学,测定雌激素受体(estrogen receptor,ER)水平,进行病理学观察.结果 ①影像学、病理观察显示D组、E组、F组肺损伤程度较B、C组减轻,其中以D组最为明显；②免疫组化结果示A组有少量的散在分布的ER；B、C、D、E、F组ER表达增加(P＜0.05),D、F组ER表达水平低于B、C、E组(P＜0.05),B、C、E组间ER表达无明显差异(P＞0.05),D组与F组ER表达无明显差异(P＞0.05).结论 ①雌激素对PQ中毒致急性肺损伤及纤维化有较明显的保护作用,抗雄激素对PQ中毒致急性肺损伤及纤维化亦有一定的保护作用,但性激素综合用药并未表现出明显的优势；②雌激素对PQ致急性肺损伤及肺纤维化的保护作用可能与ER表达下调有关.

Pathology study on effect of sex hormones on paraquat-induced acute lung injury and pulmonary fibrosis

Objective To investigate the therapeutic effects and possible mechanisms of sex hormones （estrogen, antiandrogen） on acute lung injury and pulmonary fibrosis caused by paraquat （PQ） poisoning. Methods 144 healthy clean SD male rats were randomly divided into 6 groups （n = 24 ） ： normal control group （ Group A）, toxicosis control group （ Group B）, alcohol control group （ Group C ）, estrogen （2.0 rag/kg） treatment group（Group D） , anti-androgen（ 1.0 mg/kg） treatment group （Group E）, estrogen ＋ antiandrogen treatment group（Group F）. The PQ poisoning lung injury model in rats was produced by intraperitoneal injection of PQ. Behavioral change was observed dynamically in each group. 3, 6, 15, 24 days after exposure, respectively, in each group of rats underwent chest CT scan imaging observation, lung tissue HE staining, Masson staining, immunohistochemistry （determination of estrogen receptor ER level） for pathological observation. Animals were killed after the end of the experiment. Results ①The degree of lung injury was lower in Group D , Group E and Group F compared with the Group B and Group C. The degree of lung injury was lowest in Group D; ②Immunohistochemistry showed： there was a little ER in Group A; compared with Group A, the expression of ER was more in Group B, Group C, Group D, Group E and Group F（P 〈0.05）. The expression of ER in Group D and Group F was less than that in Group B, Group C and Group E （P 〈 0.05）, but there was no difference between the two groups （ P 〉 0.05）. There was no difference among Group B, Group C and Group E （P 〉 0. 05 ）. Conclusion ①There is a significant protective effect of estrogen on lung injury and fibrosis of paraquat poisoning; anti-androgen has a protective effect on paraquat-induced lung injury and fibrosis; but there isn＇t a clear advantage by the sex hormone combination; ②The protective effect of estrogen on paraquat-induced acute lung injury and fibrosis may has relationship with the the expression of ER.