重组人脑利钠肽对急性肺损伤犬的保护作用

发布时间：2018-10-18 06:35

【摘要】：目的：应用重组人脑利钠肽（recombinant human brain natriuretic peptide，，rhBNP）对内毒素性急性肺损伤犬进行干预，从氧化-抗氧化角度说明其对肺脏具有保护作用。方法：1、急性肺损伤模型的建立。成年健康犬20只（14.2±0.45）kg，雌雄各半，随机分成4组，正常对照组（A组），急性肺损伤组（B组），急性肺损伤+rhBNP低剂量组（C组），急性肺损伤+rhBNP高剂量组（D组)。2%戊巴比妥钠30mg/kg静脉注射麻醉，实验过程中持续静脉泵入l0mg·kg-1·h-1维持。仰卧位固定，经口气管插管连接机辅助通气，呼吸频率f18次／min，潮气量Vt10ml／kg，经犬右颈内静脉穿刺及右股动脉穿刺，留置导管，导管鞘侧管接PiCCO温度探头，右股动脉导管接PICCO监测仪。除A组外，其余3组均经中心静脉在10min内注入LPS1mg/kg（生理盐水稀释至20ml，2ml/min），监测动脉血气，实验过程中各组给予平衡盐溶液以10ml/h/kg的速度进行滴注。2、给药方法及监测指标。在成功建模的基础上，正常对照组(A组，n=5)：给予等量生理盐水；急性肺损伤组（B组，n=5）：给予LPS1mg/kg+等量生理盐水；rhBNP低剂量组（C组，n=5）：给予LPS1mg/kg+rhBNP5μg/kg；rhBNP高剂量组（D组，n=5）：给予LPS1mg/kg+rhBNP10μg/kg。分别记录各组给药后0、2，4，8，12小时动物的生命体征，同时抽取动脉血用于血气分析，测定PaO2以计算氧合指数；通过PiCCO监测技术（即脉搏指示连续心排血量监测技术）监测各个时间点血管外肺水（EVLW）、肺毛细血管通透性指数（PVPI）。在12小时时处死犬，取一部分肺组织测肺湿/干比；一部分肺组织病理染色（HE染色），进行病理组织学观察；取肺组织进行MPO、MDA活性检测。结果：1、肺组织W/D与HE染色结果显示应用rhBNP低剂量组（C组）和rhBNP高剂量组（D组）均使肺水肿程度减轻，肺泡充血及出血情况均得以改善，rhBNP高剂量组（D组）改善较为明显。2、血气结果：应用rhBNP低剂量组（C组）和rhBNP高剂量组（D组）均使氧合指数得到明显提高，组织氧合得到进一步改善。PiCCO监测结果也显示肺毛细血管通透性、血管外肺水下降，得以改善。其中以rhBNP高剂量组改善更为明显。3、急性肺损伤过程中，氧化损伤严重，应用rhBNP干预明显降低了MPO、MDA的活性，减轻了肺组织氧化损伤。结论：1、rhBNP可有效减轻动物肺组织损伤，改善其功能和组织氧合、降低血管外肺水及毛细血管通透性指数，其作用成剂量效应关系。2、rhBNP可有效改善肺组织抗氧化酶活性，提示其对急性肺损伤动物的保护作用的部分机制是通过调节内源性抗氧化物酶活性来实现的。
[Abstract]:Aim: to investigate the protective effect of recombinant human brain natriuretic peptide (recombinant human brain natriuretic peptide,rhBNP) on acute lung injury induced by endotoxin in dogs. Methods: 1. Establishment of acute lung injury model. 20 adult healthy dogs (14.2 卤0.45) kg, were randomly divided into 4 groups. Normal control group (A group), acute lung injury group (B group), acute lung injury rhBNP low dose group (C group), acute lung injury rhBNP high dose group (D group). 2% pentobarbital sodium 30mg/kg was injected intravenously. Supine position was fixed, tracheal intubation connected with machine assisted ventilation, respiratory frequency f18 / min, tidal volume Vt10ml/kg, through the right internal jugular vein puncture and right femoral artery puncture, indwelling catheter, catheter sheath tube connected with PiCCO temperature probe. Right femoral artery catheter was connected with PICCO monitor. With the exception of group A, the other three groups were injected with LPS1mg/kg (diluted to 20 ml / min) into 10min via central vein to monitor arterial blood gas. During the experiment, the equilibrium salt solution was given to each group at the speed of 10ml/h/kg. On the basis of successful modeling, the normal control group (group A, n = 5) received the same amount of normal saline, the group of acute lung injury (group B, n = 5) received the same amount of normal saline, the group of low dose of rhBNP (group C, n = 5) received LPS1mg/kg rhBNP5 渭 g / kg rhBNP high dose group (group D, n 5): LPS1mg/kg rhBNP10 渭 g / kg. The vital signs of each group were recorded for 12 hours after administration, and arterial blood was extracted for blood gas analysis, and PaO2 was measured to calculate oxygenation index. Monitoring of extravascular pulmonary water (EVLW), pulmonary capillary permeability index (PVPI).) by PiCCO monitoring technique (i.e. pulse indicating continuous cardiac output monitoring technique) at different time points At 12 hours, the dogs were killed. The lung wet / dry ratio was measured in some lung tissues, the pathological staining (HE staining) in some lung tissues, and the MPO,MDA activity in lung tissues. Results: 1. Lung tissue WR / D and HE staining results showed that both rhBNP low dose group (C group) and rhBNP high dose group (D group) reduced the degree of pulmonary edema. The alveolar hyperemia and hemorrhage were improved significantly in rhBNP high dose group (D group). 2. Blood gas results: low dose rhBNP group (C group) and rhBNP high dose group (D group) significantly increased oxygenation index. Tissue oxygenation was further improved. PiCCO monitoring also showed pulmonary capillary permeability and decreased extravascular lung water. In the high dose group of rhBNP, the improvement was more obvious. 3. During acute lung injury, oxidative injury was serious. RhBNP intervention significantly decreased the activity of MPO,MDA and alleviated the oxidative injury of lung tissue. Conclusion: 1 rhBNP can effectively reduce lung injury, improve its function and tissue oxygenation, and decrease the permeability index of extravascular lung water and capillaries in a dose-dependent manner, 2rhBNP can effectively improve the activity of antioxidant enzymes in lung tissue. It is suggested that the protective mechanism of its protective effect on animals with acute lung injury may be achieved by regulating endogenous antioxidant enzyme activity.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R563.8

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