乌司他丁和Salubrinal对急性百草枯中毒大鼠的肺细胞自噬和凋亡的影响

发布时间：2018-05-28 20:07

  本文选题：百草枯中毒 + 乌司他丁　； 参考：《吉林大学》2013年硕士论文

【摘要】：目的在临床工作中，百草枯中毒患者病死率非常高，其治疗办法很少治疗方向也不明确。本文从实验动物角度去探讨在急性百草枯中毒大鼠经过乌司他丁（UTI）和Sal治疗后，肺细胞中自噬和凋亡的变化。 方法选用由吉林大学实验动物中心提供Wistar大鼠350只，体重(250±10)g，雌雄各半。空白对照组（Con）按雌雄各半原则随机选取。一次性给予1ml生理盐水灌胃，PQ染毒模型一次性给予PQ溶液40mg/kg灌胃造模，造模成功后，按雌雄各半原则随机将大鼠分为6组，每组各50只。治疗方案：Con组每日二次1ml生理盐水腹腔注射；PQ染毒组每日二次给予1ml生理盐水腹腔注射；PQ染毒UTI治疗组大鼠给予UTI（12万iu/kg）日二次腹腔注射；Sal（0.5mg/kg）治疗组大鼠PQ染毒后1、3、5天，每日一次给予Sa（l0.5mg/kg）1ml腹腔注射；PQ染毒Sa（l1.0mg/kg）治疗组大鼠PQ染毒后1、3、5天，每日一次给予Sal（1.0mg/kg）腹腔注射；PQ染毒UTI＋Sal（0.5mg/kg）治疗组，给予UTI（12万iu/kg），每日二次腹腔注射，在1、3、5天给予一次Sal（0.5mg/kg）腹腔注射；PQ染毒UTI＋Sal（1.0mg/kg）治疗组，给予UTI（12万iu/kg），每日二次腹腔注射，， PQ中毒后1、3、5天，每日一次给予Sal（1.0mg/kg）腹腔注射。染毒后第7天留取肺脏组织，行肺部HE染色观察肺组织形态，免疫组织化学法检测肺组织LC-3和Bcl-2的表达， Westernblot检测肺组织中LC-3、Bax、Bcl-2和Caspase3蛋白的表达，行统计学分析。 结果： 1HE染色结果显示：Con组大鼠肺组织形态正常；PQ染毒组肺组织结构部分破坏，部分肺泡壁塌陷，部分肺泡腔扩大，局部炎细胞浸润。可见肺泡隔显著增厚，明显的局部出血；UTI治疗组肺组织结构破坏较轻；其他组别均有不同程度的破坏。 2与PQ组相比，PU组中LC3A/B蛋白含量表达增高有统计学意义（P0.05)，PS5组和PS10组中LC3A/B蛋白含量表达降低有统计学意义（P0.05)，PUS5组和PUS10组中LC3A/B蛋白含量表达无明显变化；PU组、PS5组、 PS10组、PUS5组和PUS10组中Bcl-2/Bax蛋白含量表达增高有统计学意义（P0.05)；与PU组相比，PUS5组和PUS10组中LC3A/B和Bcl-2/Bax蛋白含量表达降低有统计学意义（P0.05)；与PS5相比，PUS5组LC3A/B和Bcl-2/Bax蛋白含量表达增高有统计学意义（P0.05)。与PS10相比，PUS10组LC3A/B和Bcl-2/Bax蛋白含量表达增高有统计学意义（P0.05) 3与Con组相比，PQ组Cleaved-Caspase3蛋白含量表达增高有统计学意义（P0.05)。与PQ组相比，PU组Cleaved-Caspase3蛋白含量表达显著降低有统计学意义（P0.01)， PS5组、PS10组、PUS5组和PUS10组中Cleaved-Caspase3蛋白含量表达降低有统计学意义（P0.05)； 4免疫组化结果显示：与相比Con组相比， PQ组LC3和Bcl-2蛋白表达量明显降低有统计学意义（P0.05）；与PQ组相比， PU组、PS5组、 PS10组、PUS5组和PUS10组LC3和Bcl-2蛋白表达量均有不同程度的改变；结论：急性PQ中毒大鼠肺组织发生内质网应激-自噬。UTI治疗急性PQ中毒时是通过增加肺组织自噬的发生，增加Bcl-2的表达和减少Caspase3依赖途径的凋亡来保护肺组织。而Sal降低了急性PQ中毒大鼠肺组织中细胞自噬的发生，增高了Bcl-2的表达，具体作用机制还有待于探讨。
[Abstract]:Objective in clinical work, the mortality of paraquat poisoning patients is very high, and the treatment methods are not very clear. In this paper, the changes of autophagy and apoptosis in lung cells after acute paraquat poisoning in rats with UTI and Sal were studied in this paper.
Methods 350 Wistar rats were selected from the experimental animal center of Jilin University, the body weight (250 + 10) g and male and female were half. The blank control group (Con) was randomly selected according to the male and female half principle. The 1ml saline was given to the stomach in one time. The PQ poisoning model was given to the PQ solution by 40mg/kg to make the gastric mold at one time. After the model was successful, the rats were randomly selected according to the male and male principle. The rats were divided into 6 groups, 50 in each group. The treatment regimen was treated in group Con two times daily 1ml saline intraperitoneal injection, and 1ml saline was given to PQ in the group of PQ for UTI (120 thousand iu/kg) for two intraperitoneal injection; Sal (0.5mg/kg) group was given 1,3,5 days after PQ poisoning. G) 1ml intraperitoneal injection; PQ infected Sa (l1.0mg/kg) group was given Sal (1.0mg/kg) intraperitoneal injection once a day after PQ exposure; PQ was administered to UTI + Sal (120 thousand) treatment group, given a daily intraperitoneal injection. UTI (120 thousand iu/kg), two times daily intraperitoneal injection, PQ poisoning after 1,3,5 days, Sal (1.0mg/kg) intraperitoneal injection once a day. After seventh days of exposure to lung tissue, lung HE staining observation of lung tissue morphology, immunohistochemical method for detection of lung tissue LC-3 and Bcl-2, Westernblot test LC-3, Bax, Bax, Bax, and eggs in lung tissue White expression, statistical analysis.
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本文编号：1948009