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目的:评价大剂量盐酸氨溴索(沐舒坦)对肺缺血再灌注损伤(Lung ischemia reperfusion injury,LIRI)的保护作用及其机制。方法:实验选取SD大鼠36只,分为三组:缺血再灌注损伤组;沐舒坦干预组;手术对照组。对大鼠进行左侧开胸并阻断左肺门根部60 min,然后进行再灌注6 h。沐舒坦干预组再灌注开始时,经股静脉持续6 h输入沐舒坦溶液(3.75 mg·kg-1·h-1)。分别检测大鼠动脉血氧分压,肺组织湿/干重比值,氧化应激因子(MDA,SOD,GSH-PX)含量,髓过氧化物酶(MPO)活力,细胞因子(TNF-α、MCP-1、TGF-β1)基因mRNA的表达水平,光镜下观察病理组织学改变。结果:(1)大剂量沐舒坦干预后,肺间质水肿、炎症细胞浸润、肺泡内出血、渗出等较再灌注损伤组明显改善(P<0.05);肺组织湿/干重比值显著降低(P<0.05);动脉血氧分压明显改善(P<0.05)。(2)大剂量沐舒坦干预后,肺组织MDA、SOD、和GSH-PX含量基本降至正常水平;MPO活力降至手术对照组水平;差异均明显低于缺血再灌注损伤组(P<0.05)。(3)沐舒坦干预组的TNF-α,MCP-1,TGF-β1基因mRNA表达水平在药物干预后虽未能恢复至正常水平,但是较缺血再灌注损伤组明显降低。结论:大剂量沐舒坦可参与下调肺组织的MDA、SOD、GSH-PX的含量和MPO活力,并通过下调TNF-α、MCP-1、TGF-β1基因mRNA的表达水平达到减轻LIRI损伤程度的目的。本研究结果表明,沐舒坦通过调控LIRI在形成过程中相关基因的表达来抑制氧化应激损伤,从而有效的减轻肺缺血再灌注损伤。
Objective: To evaluate the protective effect of ambroxol hydrochloride on lung ischemia reperfusion injury (LIRI) and its mechanism. Methods: Thirty-six SD rats were selected and divided into three groups: ischemia-reperfusion injury group, mucosolvan intervention group and operation control group. Left thoracotomy was performed in rats and the left hilar root was blocked for 60 min and then reperfused for 6 h. Mucosolvan intervention group at the beginning of reperfusion, infusion of mucosolvan (3.75 mg · kg-1 · h-1) for 6 h via the femoral vein. The arterial partial pressure of oxygen, the wet / dry weight ratio of lung tissue, the contents of oxidative stress factors (MDA, SOD, GSH-PX), myeloperoxidase (MPO) MCP-1, TGF-β1) mRNA expression levels, histopathological changes observed under light microscope. Results: (1) Mucosal edema, inflammatory cell infiltration, alveolar hemorrhage and exudation were significantly improved (P <0.05), and the ratio of wet / dry lung weight was significantly decreased P <0.05); arterial oxygen pressure was significantly improved (P <0.05). (2) MDA, SOD and GSH-PX levels in lung tissue were reduced to normal level after intervention with high dose of Mucosolvan; MPO activity decreased to the level of surgery control group, the difference was significantly lower than that of ischemia-reperfusion injury group (P < 0.05). (3) Mucosolvan intervention group TNF-α, MCP-1, TGF-β1 mRNA expression levels failed to return to normal levels after drug intervention, but was significantly lower than ischemia-reperfusion injury group. CONCLUSION: High-dose ambroxol could be involved in the down-regulation of MDA, SOD, GSH-PX and MPO activity in lung tissue, and decreased the expression of TNF-α, MCP-1 and TGF- purpose. The results of this study indicate that Mucosolvan can inhibit oxidative stress injury by regulating the expression of related genes in the process of LIRI formation, so as to reduce lung ischemia-reperfusion injury effectively.