盐酸戊乙奎醚加地塞米松治疗百草枯所致肺纤维化的实验研究

Experimental study on the therapeutic effect of penehyclidine hydrochloride plus dexamethasone on pulmonary fibrosis induced by paraquat in rats

目的研究盐酸戊乙奎醚加地塞米松对大鼠百草枯中毒所致肺间质纤维化的治疗作用及可能机制。方法 SD雄性大鼠60只,随机分为5组,每组12只,腹腔内注入质量分数为20%的百草枯溶液18mg/kg(稀释至1ml)制备大鼠百草枯中毒模型,对照组予生理盐水。给药后30min,治疗组分别向腹腔注射盐酸戊乙奎醚0.1mg/kg、地塞米松3mg/kg、地塞米松3mg/kg加盐酸戊乙奎醚0.1mg/kg,每24h重复注射1次;对照组和模型组在对应时间点给予等容积生理盐水。分别于第8天和第22天处死实验动物,检测PaO2和PaCO2,测定肺湿/干重比(W/D),观察肺组织病理形态学变化,免疫组化方法检测肺组织转化生长因子-β1(TGF-β1)的表达。结果给予百草枯后各组大鼠PaO2值显著降低,PaCO2显著增加,肺W/D和TGF-β1表达显著增加,第8天组织形态学出现急性肺炎性改变,第22天出现肺间质纤维化。盐酸戊乙奎醚、地塞米松和盐酸戊乙奎醚加地塞米松治疗都能显著提高PaO2,降低PaCO2;抑制肺组织炎性浸润,减轻纤维化;显著降低肺W/D和TGF-β1表达,且盐酸戊乙奎醚加地塞米松治疗的效果更显著。结论盐酸戊乙奎醚、地塞米松均可减轻百草枯中毒大鼠的肺组织炎症,抑制肺间质纤维化;盐酸戊乙奎醚和地塞米松有协同治疗作用。

Objective To investigate the therapeutic effects of penehyclidine hydrochloride and dexamethasone on paraquat-induced pulmonary interstitial fibrosis in rats and the possible underlying mechanisms.Methods Sixty male Sprague-Dawley rats were randomized into five groups (n = 12 each) .Paraquat of mass fraction 20% (18 mg/kg,diluted to 1 ml) was intraperitoneally administered to establish animal poisoning model,while in the control group 1 ml normal saline was injected.30 min after exposure to paraquat,the rats in the treatment group were intraperitoneally injected with penehyclidine hydrochloride 0.1 mg/kg,dexamethasone 3 mg/kg,and penehyclidine hydrochloride 0.1 mg/kg + dexamethasone 3 mg/kg,respectively,and the procedures were repeated every 24 h;with equal volume of normal saline given to the normal control group and model group at corresponding time points.On the 8th day and 22nd day respectively,experimental animals were sacrificed to detect PaO2 and PaCO2,lung wet/dry ratio (W/D) ,pathological changes of lung tissues,and determine TGF-β1 expression in lung tissues with immunohistochemistry.Results The PaO2 level significantly decreased and the level of PaCO2,pulmonary W/D and TGF-β1 expression significantly increased in each group of rats exposed to paraquat.The morphological changes presented acute pneumonia on the 8th day,while on the 22nd day,pulmonary fibrosis appeared.Penehyclidine hydrochloride,dexamethasone,and combination of penehyclidine hydrochloric + dexamethasone could significantly increase PaO2 level and decrease PaCO2 level;inhibit inflammatory infiltration in lung tissues,and reduce fibrosis;significantly reduce lung W/D and TGF-β1 expression in the lung tissues,and penehyclidine hydrochloride combined with dexamethasone had more significant therapeutic efficacy.Conclusion Both penehyclidine hydrochloride and dexamethasone may relieve lung inflammation and inhibit pulmonary fibrosis in rats with paraquat poisoning;penehyclidine hydrochloride and dexamethasone have synergistic therapeutic effect.