【作者】 任艳军；

【导师】 张新日；

【作者基本信息】 山西医科大学 ， 呼吸内科， 2010， 硕士

【摘要】 目的：通过检测不同潮气量机械通气大鼠肺组织高迁移率族蛋白1 (HMGB1) mRNA及其蛋白表达水平和血必净注射液对大潮气量机械通气大鼠肺组织HMGB1的影响,探讨HMGB1在呼吸机所致肺损伤(VILI)发病中的作用,以及血必净注射液对VILI的干预作用。方法：本实验分为两部分实验一：24只雄性健康Wistar大鼠随机分为3组,即对照组、小潮气量(L-VT)组和大潮气量(H-VT)组。采用髓过氧化物酶检测试剂盒测定各组大鼠血浆和肺泡灌洗液(BALF)中髓过氧化物酶(MPO)活性,采用免疫组织化学法(SABC法)和原位分子杂交技术检测肺组织HMGB1表达水平。实验二：24只雄性健康Wistar大鼠随机分为3组,即对照组、大潮气量组、血必净干预组。采用髓过氧化物酶检测试剂盒测定各组大鼠血浆和肺泡灌洗液中MPO活性,采用免疫组织化学法(SABC法)和原位分子杂交技术检测肺组织HMGB1表达水平。结果：实验一：1、大潮气量组大鼠血浆及BALF中MPO活性明显高于对照组和小潮气量组(均P<0.01),对照组与小潮气量组比较差异无统计学意义(P>0.05)。2、大潮气量组肺组织气道上皮细胞HMGB1mRNA及其蛋白表达水平明显高于对照组和小潮气量组(均P<0.01),小潮气量组与对照组比较差异均无统计学意义(均P>0.05)。实验二：1、大潮气量组和血必净干预组大鼠血浆及BALF中MPO活性明显高于对照组(均P<0.01)；大潮气量组大鼠血浆及BALF中MPO活性高于血必净干预组(均P<0.01)。2、大潮气量组和血必净干预组大鼠肺组织气道上皮细胞HMGB1 mRNA及其蛋白表达水平明显高于对照组(均P<0.01)；大潮气量组大鼠肺组织气道上皮细胞HMGB1 mRNA及其蛋白表达水平高于血必净干预组(均P<0.01)。结论：1、大潮气量机械通气可诱导肺组织HMGB1mRNA及其蛋白高表达,HMGB1分泌增多导致肺组织炎症反应扩大,可能是呼吸机所致肺损伤(VILI)发生的重要因素之一。2、小潮气量机械通气对肺组织HMGB1表达影响较小,对正常肺组织无明显损伤作用。3、血必净注射液在一定程度上可抑制肺组织HMGB1mRNA及其蛋白的表达,对机械通气所致大鼠急性肺损伤具有一定防治作用。更多还原

【Abstract】 Objective:To explore the role of high mobility group box 1(HMGB1) in acute lung injury induced by different tidal volume of ventilation in rats and its prevention and treatment of XueBiJing injection in the ventilaor induced lung injury by detecting the expression of high mobility group box 1(HMGB1) in lung tissue.Methods:1 Twenty-four male Wistar rats were randomly divided into three groups:control group, low tidal volume group (L-VT), high tidal volume group (H-VT). The levels of myloperoxidase(MPO) activity in plasma and bronchoalveolar lavage fluid (BALF) were determined by biochemical methods respectively.Immunohistochemial staining and molecular hybridization in situ were employed to determine the expression level of HMGB1 mRNA and protein in pulmonary tissues.2 Twenty-four male Wistar rats were divided into three groups randomly:control group, H-VT group and XueBiJing pretreatment group. The levels of myloperoxidase(MPO) activity in plasma and bronchoalveolar lavage fluid (BALF) were determined by biochemical methods respectively.Immunohistochemial staining and molecular hybridization in situ were employed to determine the expression level of HMGB1 mRNA and protein in pulmonary tissues.Results:1 Comparing with control group and low tidal volume group, the levels of MPO activity in plasma and BALF were highly significant in high tidal volume group (P＜0.01); There was no statistics meaning for the differences between low tidal volume group and control group (P>0.05).2 Comparing with control group and low tidal volume group, the expression of HMGB1 mRNA and protein were highly significant (P<0.01) in high tidal volume group. There was no statistics meaning for the differences between low tidal volume group and control group (P>0.05).3 Comparing with control group, the levels of MPO activity in plasma and BALF were highly significant in high tidal volume group and XueBiJing pretreatment group(P＜0.01); Comparing with high tidal volume group, the levels of MPO activity in plasma and BALF were decreased significant in XueBiJing pretreatment group(P<0.01).4 Comparing with control group, the expression of HMGB1 mRNA and protein was highly significant in high tidal volume group and XueBiJing pretreatment group (P＜0.01); Comparing with high tidal volume group, the expression of HMGB1 mRNA and protein was decreased significant in XueBiJing pretreatment group(P<0.01).Conclusion:1 The over expression of HMGB1 mRNA and protein can be induced by high tidal volume ventilation, which can lead to increased inflammatory response in lung tissue to expand. It is one of the most important factors in VILI.2 There is small effect on the expression of HMGB1 in lung tissue in the L-VT group and no obvious lung injury.3 XueBiJing injection may play a role of prevention and treatment in the ventilator induced lung injury by inhibiting the expression of HMGB1.更多还原