环孢素A联合地塞米松对百草枯中毒大鼠肺纤维化的治疗作用

Therapeutic effects of cyclosporine A associated with dexamethasone against paraquat-induced pulmonary interstitial fibrosis

目的探讨环孢素A联合地塞米松对急性百草枯中毒致肺纤维化大鼠的治疗作用。方法将80只SD大鼠随机分为:模型组(Mod组),地塞米松治疗组(Dex组),小剂量环孢素A治疗组联合地塞米松(Cyc-L组)和大剂量环孢素A联合地塞米松治疗组(Cyc-H组),3个治疗组根据给药疗程不同(3d、7d、14d)分为3个亚组,每组8只。采用腹腔注射20%百草枯溶液(18mg/kg)制备急性百草枯中毒肺纤维化模型。染毒后2h,Dex组经腹腔注射地塞米松(5mg/kg);Cyc-L组经腹腔注射环孢素A(5mg/kg)+地塞米松(5mg/kg);Cyc-H组经腹腔注射环孢素A(20mg/kg)+地塞米松(5mg/kg),每24h重复1次;Mod组经腹腔注射等容积生理盐水。观察大鼠一般状态,22d后处死大鼠取肺组织,检测肺组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性和羟脯氨酸(HYP)表达情况,HE染色观察肺组织病理变化。结果与Mod组相比,各治疗组肺纤维化明显减轻,肺组织MDA含量明显下降、SOD活性明显上升和HYP表达明显下降。Cyc-H组疗效又优于Dex组和Cyc-L组。7d组和14d组较3d组肺纤维化明显减轻,HYP表达下降。7d组与3d组和14d组比较肺组织MDA含量下降,SOD活性增加,差异有统计学意义(P<0.05)。结论①地塞米松或地塞米松联合环孢素A均可减轻百草枯中毒引起的肺纤维化,其中地塞米松联合大剂量环孢素A疗效优于地塞米松联合小剂量环孢素A和单纯地塞米松疗效;②7d疗程的治疗效果要好于3d和14d疗程;③地塞米松或环孢素A联合地塞米松减轻肺纤维化的可能机制是增加机体清除氧自由基能力,降低脂质过氧化水平。

Objective To investigate the therapeutic effect of cyclosporine A associated with dexamethasone on pulmonary interstitial fibrosis in experimental rats induced by paraquat poisoning.Methods 80 SD rats were randomly divided into 4 groups;model group,group treated with dexamethasone,group treated with low-dose cyclosporine A associated with dexamethasone,group treated with high-dose cyclosporine A associated with dexamethasone,then each therapeutic group was randomly divided into three subgroups again according to treatment（3d,7d and 14d）.The pulmonary interstitial fibrosis model induced by paraquat poisoning was made by intraperitoneal injection 20% paraquat solution with the dose of 18mg/kg.Two hours later,the Dex group＇rats were given the dexamethasone 5mg/kg by intraperitoneal injection;The Cyc-L group＇rats were given cyclosporine A（5mg/kg） associated with dexamethasone（5mg/kg） by intraperitoneal injection;The Cyc-H group＇rats were given cyclosporine A（20mg/kg） associated with dexamethasone（5mg/kg） by intraperitoneal injection,repeated one time every 24 hours;The Mod group＇rats were given normal saline solution with the same volume by intraperitoneal injection.Observed the changes of rats＇ behaviors,then killed the rats and measured the content of MDA,the activity of SOD and the expression of HYP in lung tissue,observed the pathology of lung tissue by HE staining at the 22th day.Results Comparing with the Mod group,pulmonary interstitial fibrosis of rats in each treatment group has been significantly released,the content of lung tissue MDA and the expression of lung tissue HYP have been significantly decreased,the activity of lung tissue SOD has been significantly increased.Effect of the Cyc-H was better than that of the Dex group and Cyc-L group.Comparing with the 3d group,pulmonary interstitial fibrosis of rats in the 7d and 14d group has been significantly released,and the expression of lung tissue HYP in the 7d and 14d group has been significantly decreased.Comparing with the 3d and 14d group,the content of lung tissue MDA in the 7d group has been significantly decreased and the activity of lung tissue SOD in the 7d group has been significantly increased.Conclusion 1 The dexamethasone and cyclosporine A associated with dexamethasone have therapeutic effects on pulmonary interstitial fibrosis induced by paraquat poisoning.Comparing with the dexamethasone and the low-dose cyclosporine A associated with dexamethasone,pulmonary interstitial fibrosis of rats in the high-dose cyclosporine A associated with dexamethasone has been significantly released;2 Therapeutic effects on pulmonary interstitial fibrosis induced by paraquat poisoning in the 7d group is better than that of the 3d and 14d group;3 It is one of the mechanisms of the therapy that dexamethasone or the cyclosporine A associated with dexamethasone can inhibit the pulmonary interstitial fibrosis of rats induced by paraquat by increasing the ability of clearing oxygen free radicals and decreasing lipid peroxide in lung tissue.