百草枯中毒大鼠肺组织线粒体中电压依赖性阴离子通路及caspase-3、8、9的变化
The effect of paraquat on voltage-dependent anion channel and caspase-3、8、9 in the mitochondria of rat lung
摘要目的 研究不同浓度百草枯(paraquat,PQ)染毒对大鼠肺组织上的线粒体线电压依赖性阴离子通路(voltage-dependent anion channel,VDAC)和caspase家族表达的影响,探讨急性百草枯中毒急性肺损伤的可能机制.方法 选取成年健康Wister大鼠200只,雌雄各半,随机分为对照组及染毒组.其中对照组100只,用1ml生理盐水一次性灌胃;染毒组100只,将PQ按50 mg/kg用生理盐水稀释到1ml,一次性灌胃染毒.分别于灌生理盐水及灌药后1、24、72、120、168 h各取20只大鼠,麻醉下解剖大鼠留取肺组织标本,分离提取线粒体并测定其VDAC及caspase-3、8、9的含量.结果 染毒后的大鼠VDAC及caspase-3、8、9的表达明显高于对照组,差异有统计学意义(P<0.001);染毒后1、24、72、120、168 h可见大鼠肺泡毛细血管内皮细胞、肺泡上皮细胞和肺间质的急性弥漫性损害,广泛肺间质炎性细胞浸润,肺泡结构紊乱,成纤维细胞明显增多等改变.结论 PQ中毒可上调大鼠肺组织线粒体VDAC及caspase-3、8、9的表达,诱导大鼠急性肺损伤的过程.
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abstractsObjective To investigate the effects of different concentrations ofparaquat (PQ) poisoning on the expression of voltage-dependent anion channel (VDAC) and caspase family in the mitochondria of rat lung tissue,and to explore possible mechanisms of acute lung injury induced by acute PQ poisoning.Methods Two hundred healthy adult Wister rats with equal numbers of male and female ones were randomly and equally divided into control group and poisoned group.The control group received one-time gastric lavage with 1 ml of normal saline,and the poisoned group with PQ (50 mg/kg) diluted in 1 ml of normal saline.Twenty rats were collected at 1,24,72,120,and 168 h after lavage with normal saline or PQ and dissected after anesthesia.Mitochondria were separated from rat lung tissue,and the content of VDAC and caspase-3,-8,and-9 were determined.Results The expression of VDAC and caspase-3,-8,and-9 in the poisoned rats were significantly higher than that in the control group (P<0.001).At 1,24,72,120,and 168 h after exposure,acute diffuse damages were found in alveolar capillary endothelial cells,alveolar epithelial cells,and pulmonary interstitial cells.Inflammatory cell infiltration in the pulmonary interstitium,alveolar structural disorder,and substantially increased fibroblasts were also found in rat lung tissue.Conclusion PQ poisoning can up-regulate the expression of VDAC and caspase-3,-8,and-9 in mitochondria of rat lung tissue to induce acute lung injury.
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