氯沙坦对机械通气大鼠肺组织TNF-α和MPO表达的影响

Effect of Losartan on the Expression of TNF-α and MPO in the Lung of Mechanically Ventilated Rats

目的通过观察AngⅡ受体拮抗剂——氯沙坦对呼吸机所致肺组织TNF-α水平和髓过氧化物酶(MPO)活性的影响,探讨氯沙坦对呼吸机所致肺损伤的保护作用。方法 24只健康雄性Wister大鼠随机分为对照组、呼吸机所致肺损伤组(VILI)和氯沙坦干预组(LAP),分别采用ELISA法测定大鼠肺组织中血管紧张素II(AngⅡ)含量,采用免疫组织化学染色法测定大鼠肺组织TNF-α蛋白表达水平,采用化学比色法测定肺组织匀浆中MPO活性。结果 VILI组大鼠肺组织AngⅡ含量、TNF-α蛋白表达水平以及肺组织匀浆中MPO活性均明显高于对照组(均P<0.01)。氯沙坦干预组大鼠肺组织AngⅡ含量与VILI组比较无明显差异(P>0.05),但肺组织TNF-α蛋白表达水平、肺组织匀浆中MPO活性和肺W/D比值均较VILI组明显降低(均P<0.01),同时肺组织病理损伤程度也较VILI组明显减轻。结论 AngⅡ通过调控肺组织中TNF-α的表达在VILI发病中起重要作用,氯沙坦可阻断AngⅡ与AT1受体的结合,下调肺组织TNF-α表达,降低MPO的活性,对VILI具有一定防治作用。

Objective To explore the effect of an AT1 inhibitor losartan on the expression of TNF-α and myeloperoxidase（MPO） in the lung of mechanically ventilated rats,and further study the protective effect of losartan on ventilator induced lung injury.Methods Twenty-four healthy male Wister rats were randomly divided into three groups： control group,ventilator induced lung injury（VILI） group and losartan group.ELISA in situ was used to determine the blood content of angiotensin II（Ang Ⅱ） in the lung tissue,immunohistochemical staining was employed to detect the expression level of TNF-α protein,and colorimetry was applied to measure the activity of myeloperoxidase（MPO） in the homogenate of lung tissue.Results The Ang Ⅱ concentration and expression level of TNF-α protein in the lung tissue,and MPO activity in the homogenate of lung tissue of the VILI group were significantly higher than those in the control group（P0.01）.There was no significant difference between the Ang Ⅱ concentration and MPO activity in the losartan group and VILI group（P0.05）.However,the expression level of TNF-α protein,MPO activity and wet/dry lung weight（W/D） ratio were significantly decreased in the losartan group in comparison with that of the VILI group（P0.01）,and the lung injury was apparently less serious than that in the VILI group.Conclusions Ang Ⅱ regulates the expression of TNF-α in the lung tissue and play an important role in the pathogenesis of ventilator-induced lung injury.Losartan may block the binding of Ang Ⅱ and AT1 receptor,down-regulate the expression of TNF-α protein and decrease the MPO activity of lung tissue homogenate,and may have preventive and therapeutic effect on ventilator-induced lung injury to some degree.