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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 investigate the effect of Telmisartan on lung tissue in ventilator-induced lung injury (VILI) rats. Methods Forty healthy male SD rats were randomly divided into spontaneous respiration control group (A group), large tidal volume mechanical ventilation group (B group), mechanical ventilation + low dose (2.5 mg / kg) telmisartan treatment group Group), mechanical ventilation + high dose (5 mg / kg) telmisartan treatment group (group D). The rat VILI model was established by using a large amount of tidal volume (40 ml / kg, 2 h). In the experiment, 4 groups of rats were given arterial blood gas and hemodynamic monitoring. 30 min before mechanical ventilation were used telmisartan solution or PBS intraperitoneal injection. The rats were killed at the scheduled time, the pathological changes of the lung tissue were observed under light microscope and the scores of Smith were determined. The expression of AT1R and PPAR-γ protein in lung tissue was detected by immunohistochemical staining. The myeloperoxidase (MPO) W / D, and the content of TNF-α and IL-8 in bronchoalveolar lavage fluid (BALF) by ELISA. Results In the experiment, the pH values of B, C and D groups tended to increase. Mean arterial pressure (MAP), arterial carbon dioxide partial pressure [p (CO2)] and oxygen partial pressure [p (O2) (P <0.05). Compared with group A, MAP, MPO, TNF-α, IL-8 and W / D in group B, C and D were significantly lower than those in group B (P <0.05, P <0.01). The protein expression of PPAR-γ was significantly decreased (P <0.05, P <0.01) and the expression of AT1R protein was significantly increased (P <0.05, P <0.01) (P <0.01), while the other indexes were significantly lower (P <0.05, P <0.01). Compared with group C, the scores of Smith, TNF-α and IL-8 in group D And AT1R protein expression (P <0.05), PPAR-γ protein expression was significantly increased (P <0.05). Conclusion Telmisartan can regulate the expression of PPAR-γ and AT1R protein, and then reduce the production of TNF-α and IL-8 in lung tissue, reduce the inflammatory reaction in lung and lung injury, Protective effects.