重組人腦利鈉肽對(duì)急性肺損傷犬的保護(hù)作用
發(fā)布時(shí)間：2018-10-18 06:35
【摘要】：目的：應(yīng)用重組人腦利鈉肽（recombinant human brain natriuretic peptide，，rhBNP）對(duì)內(nèi)毒素性急性肺損傷犬進(jìn)行干預(yù)，從氧化-抗氧化角度說(shuō)明其對(duì)肺臟具有保護(hù)作用。 方法：1、急性肺損傷模型的建立。成年健康犬20只（14.2±0.45）kg，雌雄各半，隨機(jī)分成4組，正常對(duì)照組（A組），急性肺損傷組（B組），急性肺損傷+rhBNP低劑量組（C組），急性肺損傷+rhBNP高劑量組（D組)。2%戊巴比妥鈉30mg/kg靜脈注射麻醉，實(shí)驗(yàn)過(guò)程中持續(xù)靜脈泵入l0mg·kg-1·h-1維持。仰臥位固定，經(jīng)口氣管插管連接機(jī)輔助通氣，呼吸頻率f18次／min，潮氣量Vt10ml／kg，經(jīng)犬右頸內(nèi)靜脈穿刺及右股動(dòng)脈穿刺，留置導(dǎo)管，導(dǎo)管鞘側(cè)管接PiCCO溫度探頭，右股動(dòng)脈導(dǎo)管接PICCO監(jiān)測(cè)儀。除A組外，其余3組均經(jīng)中心靜脈在10min內(nèi)注入LPS1mg/kg（生理鹽水稀釋至20ml，2ml/min），監(jiān)測(cè)動(dòng)脈血?dú)�，�?shí)驗(yàn)過(guò)程中各組給予平衡鹽溶液以10ml/h/kg的速度進(jìn)行滴注。2、給藥方法及監(jiān)測(cè)指標(biāo)。在成功建模的基礎(chǔ)上，正常對(duì)照組(A組，n=5)：給予等量生理鹽水；急性肺損傷組（B組，n=5）：給予LPS1mg/kg+等量生理鹽水；rhBNP低劑量組（C組，n=5）：給予LPS1mg/kg+rhBNP5μg/kg；rhBNP高劑量組（D組，n=5）：給予LPS1mg/kg+rhBNP10μg/kg。分別記錄各組給藥后0、2，4，8，12小時(shí)動(dòng)物的生命體征，同時(shí)抽取動(dòng)脈血用于血?dú)夥治�，測(cè)定PaO2以計(jì)算氧合指數(shù)；通過(guò)PiCCO監(jiān)測(cè)技術(shù)（即脈搏指示連續(xù)心排血量監(jiān)測(cè)技術(shù)）監(jiān)測(cè)各個(gè)時(shí)間點(diǎn)血管外肺水（EVLW）、肺毛細(xì)血管通透性指數(shù)（PVPI）。在12小時(shí)時(shí)處死犬，取一部分肺組織測(cè)肺濕/干比；一部分肺組織病理染色（HE染色），進(jìn)行病理組織學(xué)觀察；取肺組織進(jìn)行MPO、MDA活性檢測(cè)。 結(jié)果：1、肺組織W/D與HE染色結(jié)果顯示應(yīng)用rhBNP低劑量組（C組）和rhBNP高劑量組（D組）均使肺水腫程度減輕，肺泡充血及出血情況均得以改善，rhBNP高劑量組（D組）改善較為明顯。2、血?dú)饨Y(jié)果：應(yīng)用rhBNP低劑量組（C組）和rhBNP高劑量組（D組）均使氧合指數(shù)得到明顯提高，組織氧合得到進(jìn)一步改善。PiCCO監(jiān)測(cè)結(jié)果也顯示肺毛細(xì)血管通透性、血管外肺水下降，得以改善。其中以rhBNP高劑量組改善更為明顯。3、急性肺損傷過(guò)程中，氧化損傷嚴(yán)重，應(yīng)用rhBNP干預(yù)明顯降低了MPO、MDA的活性，減輕了肺組織氧化損傷。 結(jié)論：1、rhBNP可有效減輕動(dòng)物肺組織損傷，改善其功能和組織氧合、降低血管外肺水及毛細(xì)血管通透性指數(shù)，其作用成劑量效應(yīng)關(guān)系。2、rhBNP可有效改善肺組織抗氧化酶活性，提示其對(duì)急性肺損傷動(dòng)物的保護(hù)作用的部分機(jī)制是通過(guò)調(diào)節(jié)內(nèi)源性抗氧化物酶活性來(lái)實(shí)現(xiàn)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 鹵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.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R563.8
本文編號(hào)：2278298
[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 鹵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.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R563.8
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