乌司他丁对百草枯中毒大鼠肺泡上皮屏障功能的影响
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摘要
目的探讨乌司他丁(ulinastatin,UTI)对百草枯(paraquat,PQ)中毒急性肺损伤大鼠肺上皮屏障功能的影响及意义。方法将54只SD大鼠随机分为对照组(A组)、PQ组(B组)和UTI组(C组),每组各18只。B、C组以生理盐水稀释PQ 80 mg/kg一次性灌胃;C组灌胃后以UTI 100 000 U/kg腹腔注射,每日1次;A组等量生理盐水一次性灌胃。于不同处理后24、48、72 h测定肺泡上皮通透性(AEP)、肺泡内液体清除率(ALCR)、总肺水量(TLW)和肺血管外肺水量(EVLW);原位末端缺刻标记法(TUNRL)检测肺泡上皮细胞凋亡情况;观察肺组织病理学改变;并进行肺损伤半定量评分。结果与A组比较,B组大鼠中毒后24、48、72 h ALCR显著降低,TLW、EVLW及AEP呈明显升高趋势(P<0.05或P<0.01)。与B组比较,C组大鼠中毒后24、48、72 h ALCR均明显升高,TLW、EVLW及AEP呈明显降低趋势(P<0.05或P<0.01),且肺组织的水肿、出血、炎症程度、局部出血及损伤学评分和肺湿/干重比均明显好转。结论百草枯中毒并急性肺损伤大鼠存在严重的肺泡上皮屏障功能障碍;乌司他丁通过抑制肺泡上皮细胞凋亡,可改善肺泡上皮功能障碍,减轻肺损伤程度。
Objective To investingate the effect of ulinastatin on alveolar epithelial barrier in rats with lung injury by acute paraquat poisoning.Methods 54 Sprague-Dawley(SD)rats were randomly divided into three experimental groups:control group(group A),paraquat poisoning group(group B)and UTI treating group(group C),18 in each group.Rats in group B and group C were administered intragastrically with 80 mg/kg PQ;rats in group C were additionally injected peritoneally with 100 000 U/kg ulinastatin immediately after PQ exposure,once a day;rats in group A were administered intragastrically with the same volume of saline only.The alveolar liquid elearance rate(ALCR),total lung water content(TLW),extravascular lung water content(EVLW)and alveolar epithelial permeability(AEP)were examined at 24,48 and 72 h after poisoning respectively.Meantime,the alveolar epithelium apoptosis was detected by TUNEL and lung pathological changes was evaluated by Smith lung injury score as well.Results The results showed that there were continuous increase in levels of AEP,TLW and EVLW,while the level of ALCR was reduced in group B compared with group A at 24,48,72 h after poisoning,respectively.Compared with group B,there was continuous decrease of AEP,TLW and EVLW,while the level of ALCR presented rised trend in group C at 24,48,72 h after poisioning,additionally,the pathological changes in lung tissue of PQ poisoning such as congestion,edema,leukocytes infiltration and local hemorrhage,damage score and wet/dry ratio of lung tissue in group C were all significantly improved.Conclusion The results suggested that there is severe pulmonary alveolar barrier in acute lung injury rats by paraquat,UTI can significantly improve alveolar epithelial barrier function,reduce lung injury from PQ-ALI rats that may be by inhibiting the apoptosis of pulmonary epithelial cells.
Objective To investingate the effect of ulinastatin on alveolar epithelial barrier in rats with lung injury by acute paraquat poisoning.Methods 54 Sprague-Dawley(SD)rats were randomly divided into three experimental groups:control group(group A),paraquat poisoning group(group B)and UTI treating group(group C),18 in each group.Rats in group B and group C were administered intragastrically with 80 mg/kg PQ;rats in group C were additionally injected peritoneally with 100 000 U/kg ulinastatin immediately after PQ exposure,once a day;rats in group A were administered intragastrically with the same volume of saline only.The alveolar liquid elearance rate(ALCR),total lung water content(TLW),extravascular lung water content(EVLW)and alveolar epithelial permeability(AEP)were examined at 24,48 and 72 h after poisoning respectively.Meantime,the alveolar epithelium apoptosis was detected by TUNEL and lung pathological changes was evaluated by Smith lung injury score as well.Results The results showed that there were continuous increase in levels of AEP,TLW and EVLW,while the level of ALCR was reduced in group B compared with group A at 24,48,72 h after poisoning,respectively.Compared with group B,there was continuous decrease of AEP,TLW and EVLW,while the level of ALCR presented rised trend in group C at 24,48,72 h after poisioning,additionally,the pathological changes in lung tissue of PQ poisoning such as congestion,edema,leukocytes infiltration and local hemorrhage,damage score and wet/dry ratio of lung tissue in group C were all significantly improved.Conclusion The results suggested that there is severe pulmonary alveolar barrier in acute lung injury rats by paraquat,UTI can significantly improve alveolar epithelial barrier function,reduce lung injury from PQ-ALI rats that may be by inhibiting the apoptosis of pulmonary epithelial cells.
引文
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[12]周从阳,张志坚,罗雅娟,等.乌司他丁对百草枯染毒大鼠肺组织热休克蛋白70和核转录因子-κB的影响[J].中华劳动卫生职业病杂志,2011,29(4):380-383.
[13]马晓辉,梁显泉,虞晓红,等.乌司他丁对脓毒症大鼠肺脏的保护作用[J].中华急诊医学杂志,2011,20(1):52-55.
[14]孙明莉,李海峰,刘晓亮,等.乌司他丁对百草枯中毒肺纤维化的影响及其机制研究[J].中国危重病急救医学,2011,23(3):187-188.
[2]马增秀,王文生,卢青龙,等.急性百草枯中毒106例临床分析[J].中华劳动卫生职业病杂志,2009,27(8):493-494.
[3]张宝兰,姚朗,欧艺.1991～2008年我国百草枯中毒文献分析[J].中国急救医学,2010,30(2):139-141.
[4]Matthay M A,Cleriei C,Saumon G.Invited review:Active fluidclearance from the distal air spaces of the lung[J].J Appl Physilo,2002,93(4):1533-1541.
[5]Osman M O,Kristensen J U,Jacobsen N O,et al.A monoclonalantiinterleukin 8 antibody(WS-4)inhibits cytokine response andacute lung injury in experimental severe acute necrotizing pancreastitisin rabbits[J].Gut,1998,43(2):232-239.
[6]Rezaiguias S,Carat C,Delelaux C,et al.Acute bacterial pneumo-nia in rats increases alveolar epitllelial fluid clearance by a tumor nec-rosis factor-alpha-dependent mechanism[J].J Clin Invest,1997,99(2):325-335.
[7]Noble W H,Obdrzalek J,Kay J C.A new technique for measuring pul-monary edema[J].J Appl Physiol,1973,34(4):508-512.
[8]周从阳,张志坚,龚少峰,等.百草枯中毒大鼠肺组织热休克蛋白70表达及乌司他丁干预研究[J].中华急诊医学杂志,2010,19(9):953-956.
[9]Zhuang J J,Li X P,Uhal B D,et al.Apoptosis-dependent acutepulmonary injury after intratracheal instillation of angiotensinⅡ[J].Acta Physiologica Sinica,2008,60(6):715-722.
[10]Ito K,Mizutani A,Kira S,et al.Effect of Ulinastatin,a humanurinary typsin inhibitor,on the oleic acid-induced acute lung injuryin rats via the inhibition of activated leukocytes[J].Injury,2005,26(3):387-394.
[11]Bao P,Gao W,Li S,et al.Effect of pretreatment with high-doesulinastatin in preventing radiateon-induced pulmonary injury in rats[J].Eur J Phamaclo,2009,603(1/3):114-119.
[12]周从阳,张志坚,罗雅娟,等.乌司他丁对百草枯染毒大鼠肺组织热休克蛋白70和核转录因子-κB的影响[J].中华劳动卫生职业病杂志,2011,29(4):380-383.
[13]马晓辉,梁显泉,虞晓红,等.乌司他丁对脓毒症大鼠肺脏的保护作用[J].中华急诊医学杂志,2011,20(1):52-55.
[14]孙明莉,李海峰,刘晓亮,等.乌司他丁对百草枯中毒肺纤维化的影响及其机制研究[J].中国危重病急救医学,2011,23(3):187-188.