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目的研究血管紧张素Ⅱ受体阻断剂洛沙坦对大鼠机械通气所致肺损伤(VILI)的保护作用及其机制。方法40只健康SD大鼠随机均分成A、B、C、D四组:A组为对照组;B组为正常潮气量机械通气组,潮气量(V_T)为10 ml/kg;C组为大潮气量机械通气通气组,V_T为40 ml/kg;D组为大潮气量通气加洛沙坦处理组,V_T为40 ml/kg,D组大鼠实验前30 min用血管紧张素Ⅱ受体(AT1型)特异性阻断剂洛沙坦(Losartan)溶液30 mg/kg腹腔注射。B、C、D三组机械通气频率(P)均为80次/min,通气时间均为2 h。实验完毕收集肺组织和肺泡灌洗液标本。光镜观察肺病理改变,逆转录聚合酶链式反应(RT-PCR)法检测A、B、C三组肺组织中血管紧张素原的表达水平,TUNEL法检测肺组织细胞凋亡情况,同时测定肺灌洗液总蛋白、白细胞计数、肺湿/干比以及肺组织髓过氧化物酶(MPO)的水平。结果B组和A组各项指标差异无统计学意义;与A、B组相比,C组肺病理改变明显,肺细胞凋亡显著性增多,血管紧张素原的表达水平显著增高(P<0.01),肺湿/干比、总蛋白、白细胞计数、MPO等指标均显著性增高(P<0.01);与C组比较,D组肺病理改变明显减轻,肺细胞凋亡、肺湿/干比、总蛋白、白细胞计数、MPO等指标均显著性降低(P<0.05或P<0.01)。结论血管紧张素Ⅱ可能在VILI的致病机理中起着一定的作用,特异性阻断血管紧张素Ⅱ受体(AT1型)能显著减轻VILI时肺损伤和炎症反应的程度。
Objective To investigate the protective effect and mechanism of losartan, an angiotensin Ⅱ receptor blocker, on lung injury induced by mechanical ventilation in rats. Methods Forty healthy SD rats were randomly divided into four groups (A, B, C and D): group A as control group; group B as normal tidal volume mechanical ventilation group with tidal volume (V_T) of 10 ml / kg; Large tidal volume of mechanical ventilation group, V_T was 40 ml / kg; group D was large tidal volume ventilation and losartan treatment group, V_T was 40 ml / kg, D group rats 30 min before the experiment with angiotensin Ⅱ receptor AT1 type) specific blocking agent Losartan solution 30 mg / kg intraperitoneal injection. B, C, D three groups of mechanical ventilation frequency (P) were 80 beats / min, ventilation time is 2 h. After the experiment, lung tissue and alveolar lavage fluid samples were collected. Lung pathological changes were observed with light microscope. The expression of angiotensinogen in lung tissues of groups A, B and C was detected by reverse transcription-polymerase chain reaction (RT-PCR), apoptosis of lung tissue was detected by TUNEL, Pulmonary perfusion fluid total protein, white blood cell count, lung wet / dry ratio and lung tissue myeloperoxidase (MPO) levels were measured. Results The indexes of group B and group A had no significant difference. Compared with group A and group B, the pathological changes of lung in group C were obvious, the apoptosis of lung cells was significantly increased and the expression of angiotensinogen was significantly increased (P < 0.01), lung wet / dry ratio, total protein, white blood cell count, MPO and other indicators were significantly increased (P <0.01); compared with the C group, D group lung pathological changes significantly reduced lung cell apoptosis, lung wet / Ratio, total protein, white blood cell count, MPO and other indicators were significantly lower (P <0.05 or P <0.01). Conclusion Angiotensin Ⅱ may play a role in the pathogenesis of VILI. Blocking angiotensin Ⅱ receptor (AT1) can significantly reduce the degree of lung injury and inflammation in VILI.