摘要
目的研究替米沙坦对呼吸机相关性肺损伤(ventilator-induced lung injury,VILI)大鼠肺组织的影响。方法40只健康雄性SD大鼠随机均分为自主呼吸对照组(A组)、大潮气量机械通气组(B组)、机械通气+小剂量(2.5 mg/kg)替米沙坦处理组(C组)、机械通气+大剂量(5 mg/kg)替米沙坦处理组(D组)。采用大潮气量(40 ml/kg,2 h)建立大鼠VILI模型。实验中4组大鼠均给予动脉血气和血流动力学监测。机械通气前30 min分别采用替米沙坦溶液或PBS腹腔注射。实验至预定时间处死大鼠,光镜下观察肺组织病理改变并作Smith评分,免疫组织化学染色法检测肺组织中AT1R和PPAR-γ蛋白的表达,测定髓过氧化物酶(myeloperoxidase,MPO)活性及肺湿干质量比值(W/D),ELISA法测定支气管肺泡灌洗液(BALF)中TNF-α及IL-8含量。结果实验中B、C、D组pH值呈升高趋势,平均动脉压(MAP)、动脉血二氧化碳分压[p(CO2)]及氧分压[p(O2)]呈下降趋势;通气2 h后,与B组比较,C、D组MAP明显降低(P<0.05);与A组比较,B、C、D组Smith评分、MPO活性、TNF-α和IL-8含量及W/D比值显著升高(P<0.05,P<0.01),PPAR-γ蛋白表达显著下降(P<0.05,P<0.01),AT1R蛋白表达显著增加(P<0.05,P<0.01);与B组比较,C、D组PPAR-γ蛋白表达显著增加(P<0.01),其余指标明显降低(P<0.05,P<0.01);与C组比较,D组Smith评分、TNF-α及IL-8含量及AT1R蛋白表达显著降低(P<0.05),PPAR-γ蛋白表达显著增加(P<0.05)。结论替米沙坦通过调节PPAR-γ、AT1R蛋白的表达,继而减少肺组织内致炎因子TNF-α与IL-8的产生,减缓肺内炎症反应及肺组织损伤程度,对VILI肺起到保护作用。
Objective To determine the effect of telmisartan on ventilator-induced lung injury（VILI） in rats.Methods Forty healthy male SD rats were equally divided into four groups in random（A,B,C and D groups,n=10）.Group A served as control group,in which rats did not receive ventilation.Groups B,C and D received large-tide volume ventilation,but only rats from groups C and D received intraperitoneal injection with telmisartan solution（2.5 and 5 mg/kg respectively.Telmisartan was dissolved in PBS） in 30 min before ventilation.Equal amount of PBS solution was given to rats in groups A and B.A rat model of VILI was reproduced by volume-controlled mechanical ventilation with large tide volume（Vt=40 ml/kg for 2 h）.Hemodynamic parameters and arterial blood gases of all the rats in the 4 groups were measured throughout the study period.After maintaining ventilation for 2 h,all rats were sacrificed and specimens of lung tissues and bronchoalveolar lavage fluid（BALF） were harvested.Lung pathological changes were observed by microscopy,and Smith score was estimated.The protein levels of peroxisome proliferator activated receptor-γ（PPAR-γ） and AngⅡ1 receptor（AT1R） in lung tissues were assayed with immunohistochemistry staining.Lung myeloperoxidase（MPO） activity and wet-dry weight ratio（W/D） were measured.The levels of tumor necrosis factor-α（TNF-α） and interleukin-8（IL-8） in BALF were measured by enzyme-linked immunosorbent assay（ELISA）.Results Mean pH values in arterial blood from groups B,C and D tended to be higher than the base line value during the ventilation,while mean arterial pressure（MAP）,mean partial pressure of carbon dioxide in arterial blood [p（CO2）] and mean partial pressure of oxygen in arterial blood were lower than baseline in these groups.MAP in groups C and D was significantly lower than in group B after 2 hours＇ ventilation（P0.05）.Smith score,mean MPO activity,mean W/D ratio,concentration of TNF-α and IL-8 in groups B,C and D were significantly higher than in group A（P0.05,P0.01）.The protein expression of PPAR-γ in groups of B,C and D was significantly lower than in group A（P0.05,P0.01）,but that of AT1R was significantly higher than group A（P0.05,P0.01）.Besides the protein expression of PPAR-γ,the rest parameters,such as Smith score,mean MPO activity,mean W/D ratio,protein expression of AT1R,and the concentrations of TNF-α and IL-8 in groups C and D were significantly lower than in group B（P0.05,P0.01）.What＇s more,Smith score,concentration of TNF-α and IL-8 and protein expression of AT1R in groups of D were significantly lower than group C（P0.05）,and the protein expression of PPAR-γ was significantly higher in group D（P0.05）.Conclusion These results suggest that telmisartan attenuates VILI probably through regulating PPAR-γ and AT1R,decreasing the productions of the inflammation factors TNF-α and IL-8,and then slowing down the inflammatory response and lung injury in the lung issue.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2012年第4期315-319,共5页
Journal of Third Military Medical University
基金
广西壮族自治区自然科学基金(2010GXNSFA013253)~~
关键词
机械通气
呼吸机相关性肺损伤
替米沙坦
大鼠
mechanical ventilation
ventilator-induced lung injury
Telmisartan
mice
