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替米沙坦对大鼠机械通气所致肺损伤保护作用的实验研究

发布时间:2019-05-03 19:01
【摘要】:目的:通过研究替米沙坦对机械通气所致肺损伤(ventilator-induced lung injury,VILI)肺组织的病理改变和肺泡中炎性细胞因子水平的影响,探讨替米沙坦对VILI的保护作用及可能的机制。 方法:采用大潮气量-容量控制通气(VCV)模式建立大鼠VILI动物模型。40只成年健康雄性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(2.5mg/Kg)替米沙坦处理组(C组)、机械通气+大剂量(5mg/kg)替米沙坦处理组(D组)。实验中4组大鼠均给予动脉血气和血流动力学监测, B、C、D组大鼠给予相同的通气参数进行容量控制通气:潮气量(Vt)为40ml/Kg;呼吸频率为40次/分;吸气/呼吸时间比值(I/E)为1:2;呼吸末正压(PEEP)为0;吸入气体为室内空气,实验时间为2小时。机械通气前30min分别采用等量的替米沙坦(Telmisartan)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(MPO)活性及肺湿干重比值(W/D),酶联免疫吸附测定(ELISA)法测定支气管肺泡灌洗液(BALF)中TNF-α及IL-8含量。 结果:未行机械通气前,四组大鼠动脉血PH值、平均动脉压(MAP)动脉血二氧化碳分压(PaCO2)及氧分压(PO2)均无显著性差异;实验中B、C、D组PH值呈升高趋势,MAP、PaCO2及PO:呈下降趋势;通气2小时后,与B组比较,C、D组MAP明显降低(P0.05);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(P0.05,P0.01),PPAR-γ蛋白表达显著下降(P0.05,P0.01),AT1R蛋白表达显著增加(P0.05,P0.01);与B组比较,C、D组PPAR-γ蛋白表达显著增加(P0.01),其余指标明显降低(P0.05,P0.01);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(P0.05),PPAR-γ蛋白表达显著增加(P0.05)。 结论:预先应用替米沙坦可显著减轻机械通气所致大鼠肺组织的损伤性改变。替米沙坦对VILI保护作用的机制可能是肺通过调节肺组织中PPAR-γ、 AT1R蛋白的表达,抑制肺组织内炎性细胞因子TNF-α与工L-8的合成与释放,减少肺内中性粒细胞的募集,从而减轻肺组织的损伤。
[Abstract]:Aim: to study the effect of telmisartan on the pathological changes of lung tissue and the level of inflammatory cytokines in alveolar tissue after mechanical ventilation-induced lung injury (ventilator-induced lung injury,VILI), and to explore the protective effect of telmisartan on VILI and its possible mechanism. Methods: 40 adult healthy male SD rats were randomly divided into control group (group A) and mechanical ventilation group (group B) with high tidal volume-volume controlled ventilation (VCV) model to establish VILI model of rats, and 40 healthy adult male SD rats were randomly divided into two groups: control group (group A) and mechanical ventilation group (group B). Low-dose mechanical ventilation (2.5mg/Kg) and telmisartan-treated group (group C) and high-dose mechanical ventilation (5mg/kg)-telmisartan-treated group (group D). Arterial blood gas and hemodynamics were monitored in all the four groups. Group B, C, D were given the same ventilation parameters for volume control ventilation: tidal volume (Vt) was 40 ml / kg, respiratory rate was 40 times / min (P < 0.01), and group B, C and D were given the same ventilation parameters for volume control ventilation. The inspiratory / respiratory time ratio (I / E) was 1-2; the positive end-breathing pressure (PEEP) was 0; the inhaled gas was indoor air and the experiment time was 2 hours. 30min was injected intraperitoneally with telmisartan (Telmisartan) solution or PBS before mechanical ventilation. The rats were killed at the scheduled time. The pathological changes and Smith score of lung were observed under light microscope. The expression of AT1R and PPAR- 纬 protein in lung tissue was detected by immunohistochemical staining. Myeloperoxidase (MPO) activity and lung wet-dry weight ratio (W / D) were measured. TNF- 伪 and IL-8 contents in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Results: before mechanical ventilation, there was no significant difference in arterial PH, mean arterial pressure (MAP), arterial partial pressure of carbon dioxide (PaCO2) and partial pressure of oxygen (PO2) among the four groups. After 2 hours of ventilation, MAP in group C and D was significantly lower than that in group B (P 0.05), but MAP,PaCO2 and PO: in group B, C, D were significantly lower than those in group B (P 0.05). Compared with group A, Smith score, MPO activity, content of TNF- 伪 and IL-8, and ratio of W / D were significantly increased in group B, C and D (P 0.05, P0.01), while expression of PPAR- 纬 protein was significantly decreased (P 0.05, P0.01), and that in group B, C, D was significantly higher than that in group A (P 0.05, P0.01). The expression of AT1R protein was significantly increased (P0.05, P0.01). Compared with group B, the expression of PPAR- 纬 protein in group C and D increased significantly (P0.01), while the other indexes decreased significantly (P0.05, P0.01). Compared with group C, Smith score, content of TNF- 伪 and IL-8 and expression of AT1R protein in group D were significantly lower than those in group C (P0.05), while expression of PPAR- 纬 protein was significantly increased (P0.05). Conclusion: telmisartan can relieve lung injury induced by mechanical ventilation in rats. The protective mechanism of telmisartan on VILI may be that lung reduces the recruitment of neutrophils by regulating the expression of PPAR- 纬 and AT1R proteins and inhibiting the synthesis and release of inflammatory cytokines TNF- 伪 and L-8 in lung tissue. In order to reduce the lung tissue damage.
【学位授予单位】:桂林医学院
【学位级别】:硕士
【学位授予年份】:2012
【分类号】:R563.8

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相关期刊论文 前2条

1 王建春;姜鹏;黄建;钱桂生;;急性肺损伤大鼠肺组织PPAR-γ表达的研究[J];第三军医大学学报;2008年06期

2 冯丹;姚尚龙;尚游;武庆平;王立奎;;血管紧张素Ⅱ受体阻断剂对大鼠机械通气所致肺损伤的保护作用[J];中华急诊医学杂志;2007年09期



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