α1-抗胰蛋白酶mRNA在油酸致急性肺损伤大鼠肺组织中的表达
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摘要
研究背景:急性肺损伤(acute lung injury,ALI)是一种由肺内或肺外致病因素诱发的严重的病理状态,其早期的病理改变主要表现为:肺间质水肿,中性粒细胞等炎症细胞侵润,肺泡腔被富含蛋白及炎症细胞的液体充填。中性粒细胞在ALI病理机制形成中发挥着重要的作用。其病理损伤作用主要通过释放蛋白酶等多种生物活性物质实现,中性粒细胞弹性蛋白酶(neutrophil elastase,NE)可以分解弹性蛋白等多种蛋白质,对肺组织产生破坏,是ALI中的重要损伤性物质。α1-抗胰蛋白酶(α1-antitrypsin,AAT)是一种主要由肝细胞、巨噬细胞等产生的中性粒细胞弹性蛋白酶抑制剂(neutrophil elastase inhibitor,NEI),是维持机体蛋白酶—抗蛋白酶平衡的重要物质。以往的研究表明,肺泡II型上皮细胞、支气管上皮细胞等肺组织细胞也能够表达AAT。但在ALI时肺组织中AAT的表达情况目前尚不清楚。
目的:观察油酸诱导的ALI大鼠肺组织中AATmRNA的表达情况,探讨肺组织局部表达的AATmRNA在ALI中的作用。
方法:SD大鼠32只,随机分为:对照组及油酸致ALI4小时组(A组)、8小时组(B组)、16小时组(D组),每组8只。对照组予以生理盐水0.20ml/kg尾静脉注射, 4小时抽取主动脉血后处死动物取标本。油酸致ALI各组予以油酸0.20ml/kg尾静脉注射,分别在注射油酸后4、8、16小时,自腹主动脉抽血用于血PaO2检测,并计算氧合指数。剪断腹主动脉放血处死动物,取左肺中部肺组织,采用RT-PCR检测肺组织AATmRNA;取左肺上部组织制作切片,光镜观察;取左肺下部组织测湿/干重比(W/D);取右肺行支气管肺泡灌洗,测定支气管肺泡灌洗液(BALF)中的中性粒细胞数百分比及白蛋白含量。
结果:光镜观察大鼠肺组织切片结果显示:对照组大鼠肺组织结构正常,肺泡壁薄,未见明显炎症细胞侵润及出血水肿。A组、B组、D组大鼠肺组织结构破坏,肺泡壁增厚,可见大量炎症细胞侵润及肺泡出血。肺组织W/D最大的是D组,与对照组比较差异有显著性(P<0.01),与B组比较差异有显著性(P<0.05);A组较对照组升高,差异有显著性(P<0.01)。A组、B组、D组BALF中白蛋白含量与对照组比较差异均有显著性(P<0.01),三组间结果比较差异无显著性(P>0.05)。BALF中性粒细胞数百分比:A组、B组、D组均显著高于对照组(P<0.01),其中A组与D组比较差异有显著性(P<0.05)。对照组氧合指数正常,油酸致ALI各组氧合指数均降低,4小时氧合指数为291±7.95,与对照组(451.79±5.93)比较,差异具有显著性(P<0.01);至8～16小时氧合指数下降更为显著(B组及D组与对照组比较差异有显著性,P<0.01;两组间比较差异有显著性,P<0.05)。油酸致ALI大鼠肺组织AATmRNA的表达自4小时开始呈线性升高,与对照组比较差异具有显著性(P<0.01);并于16小时达峰值,与对照组比较差异具有显著性(P<0.01)。
结论:油酸致ALI时,大鼠肺组织AATmRNA的表达上调;肺组织局部表达的AATmRNA参与了ALI的病理过程。
OBJECTIVE To observe the expression ofα1-antitrypsin mRNA in lung tissues of acute lung injury induced by oleic aicd in SD rats,and to investigate the function ofα1-antitrypsin mRNA expressed in local lung tissues of rats in acute lung injury.
METHODS Models of acute lung injury in rats were induced by oleic aicd(oleic aicd,0.20ml/kg,iv). A total of 32 SD rats were randomly divided into 4 groups (n=8 each)as follows:the control group , the acute lung injury groups induced by oleic aicd ,4 hours group(group A), 8 hours group (group B)and 16 hours group(group D).We infused normal saline via the tail vein for control group,and oleic aicd for group A , group B and group D.The rats were sacrificed by bleeding at 4h、8 h and 16h after intravenous oleic aicd administration,and at 4h after intravenous normal saline administration.As the meantime arterial blood gases were analysed.Then the lungs were removed,the middle lobes of the left lungs were obtained forα1-antitrypsin mRNA analyse by RT-PCR and the lower lobes of the left lungs for detecting the ratio of wet to dry as well as the top lobes for pathological section analyzing .Cells in right bronchoalvenar lavage fluid (BALF) were counted and the percentage of PMN were classified in sediment film,and albumin concentration of BALF were measured.
RESULT The expression ofα1-antitrypsin mRNA which was very low in control group,however significantly increased in ALI group induced by oleic aicd at 4 hours(P<0.01);the increase inα1-antitrypsin mRNA was linear from 4 h until 16 h after intravenous oleic aicd administration ;and reached peak at 16 hours (P<0.01). As compared to the control grounp , the structures of pulmonary alveoli in group A、B and D were demolished,and infiltration of polymorphologic cells , widen alveolar wall and local hemorrhage in alveolar wall were found. The amount of PMN and albumin in BALF of grounp A、B and D was significantly increased(P<0.01). Compared with control grounp,the arterial blood oxygen pressures decreased significantly in group A、B and D(P<0.01).The ratio of wet to dry in group B and D were significantly higher than those in group A and control grounp(P<0.01). CONCLUSIONS The expression ofα1-antitrypsin mRNA in local lung tissues of rats in ALI induced by oleic aicd,was significantly increased.α1-antitrypsin mRNA which were expressed in local lung tissues participated in the pathogenesis of acute lung injury.
目的:观察油酸诱导的ALI大鼠肺组织中AATmRNA的表达情况,探讨肺组织局部表达的AATmRNA在ALI中的作用。
方法:SD大鼠32只,随机分为:对照组及油酸致ALI4小时组(A组)、8小时组(B组)、16小时组(D组),每组8只。对照组予以生理盐水0.20ml/kg尾静脉注射, 4小时抽取主动脉血后处死动物取标本。油酸致ALI各组予以油酸0.20ml/kg尾静脉注射,分别在注射油酸后4、8、16小时,自腹主动脉抽血用于血PaO2检测,并计算氧合指数。剪断腹主动脉放血处死动物,取左肺中部肺组织,采用RT-PCR检测肺组织AATmRNA;取左肺上部组织制作切片,光镜观察;取左肺下部组织测湿/干重比(W/D);取右肺行支气管肺泡灌洗,测定支气管肺泡灌洗液(BALF)中的中性粒细胞数百分比及白蛋白含量。
结果:光镜观察大鼠肺组织切片结果显示:对照组大鼠肺组织结构正常,肺泡壁薄,未见明显炎症细胞侵润及出血水肿。A组、B组、D组大鼠肺组织结构破坏,肺泡壁增厚,可见大量炎症细胞侵润及肺泡出血。肺组织W/D最大的是D组,与对照组比较差异有显著性(P<0.01),与B组比较差异有显著性(P<0.05);A组较对照组升高,差异有显著性(P<0.01)。A组、B组、D组BALF中白蛋白含量与对照组比较差异均有显著性(P<0.01),三组间结果比较差异无显著性(P>0.05)。BALF中性粒细胞数百分比:A组、B组、D组均显著高于对照组(P<0.01),其中A组与D组比较差异有显著性(P<0.05)。对照组氧合指数正常,油酸致ALI各组氧合指数均降低,4小时氧合指数为291±7.95,与对照组(451.79±5.93)比较,差异具有显著性(P<0.01);至8～16小时氧合指数下降更为显著(B组及D组与对照组比较差异有显著性,P<0.01;两组间比较差异有显著性,P<0.05)。油酸致ALI大鼠肺组织AATmRNA的表达自4小时开始呈线性升高,与对照组比较差异具有显著性(P<0.01);并于16小时达峰值,与对照组比较差异具有显著性(P<0.01)。
结论:油酸致ALI时,大鼠肺组织AATmRNA的表达上调;肺组织局部表达的AATmRNA参与了ALI的病理过程。
OBJECTIVE To observe the expression ofα1-antitrypsin mRNA in lung tissues of acute lung injury induced by oleic aicd in SD rats,and to investigate the function ofα1-antitrypsin mRNA expressed in local lung tissues of rats in acute lung injury.
METHODS Models of acute lung injury in rats were induced by oleic aicd(oleic aicd,0.20ml/kg,iv). A total of 32 SD rats were randomly divided into 4 groups (n=8 each)as follows:the control group , the acute lung injury groups induced by oleic aicd ,4 hours group(group A), 8 hours group (group B)and 16 hours group(group D).We infused normal saline via the tail vein for control group,and oleic aicd for group A , group B and group D.The rats were sacrificed by bleeding at 4h、8 h and 16h after intravenous oleic aicd administration,and at 4h after intravenous normal saline administration.As the meantime arterial blood gases were analysed.Then the lungs were removed,the middle lobes of the left lungs were obtained forα1-antitrypsin mRNA analyse by RT-PCR and the lower lobes of the left lungs for detecting the ratio of wet to dry as well as the top lobes for pathological section analyzing .Cells in right bronchoalvenar lavage fluid (BALF) were counted and the percentage of PMN were classified in sediment film,and albumin concentration of BALF were measured.
RESULT The expression ofα1-antitrypsin mRNA which was very low in control group,however significantly increased in ALI group induced by oleic aicd at 4 hours(P<0.01);the increase inα1-antitrypsin mRNA was linear from 4 h until 16 h after intravenous oleic aicd administration ;and reached peak at 16 hours (P<0.01). As compared to the control grounp , the structures of pulmonary alveoli in group A、B and D were demolished,and infiltration of polymorphologic cells , widen alveolar wall and local hemorrhage in alveolar wall were found. The amount of PMN and albumin in BALF of grounp A、B and D was significantly increased(P<0.01). Compared with control grounp,the arterial blood oxygen pressures decreased significantly in group A、B and D(P<0.01).The ratio of wet to dry in group B and D were significantly higher than those in group A and control grounp(P<0.01). CONCLUSIONS The expression ofα1-antitrypsin mRNA in local lung tissues of rats in ALI induced by oleic aicd,was significantly increased.α1-antitrypsin mRNA which were expressed in local lung tissues participated in the pathogenesis of acute lung injury.
引文
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