p38-MAPK在戊乙奎醚保护内毒素致新生大鼠急性肺损伤效应中的作用

发布时间：2018-03-18 22:39

本文选题：盐酸戊乙奎醚　切入点：内毒素　出处：《郑州大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:观察盐酸戊乙奎醚(PHC)预处理对内毒素(细菌脂多糖,LPS)致大鼠急性肺损伤(acute lung injury,ALI)时p38丝裂原活化蛋白激酶(p38-MAPK)表达的影响,探讨盐酸戊乙奎醚对ALI的肺保护机制,为急性肺损伤的预防和治疗提供新思路。方法:本实验分为两部分。第一部分:30只7日龄新生SD大鼠,体重16至22克,随机分为三组(n=10):生理盐水组(A组)、内毒素组(B组)、盐酸戊乙奎醚组(C组)。A组仅腹腔注射生理盐水0.5ml,B组腹腔注射内毒素5mg/kg加生理盐水稀释至5ml造成急性肺损伤模型,C组在腹腔注射内毒素前30min腹腔注射盐酸戊乙奎醚2mg/kg加生理盐水稀释至5ml。造模6h后麻醉下取大鼠肺组织,测量肺组织湿/干重比(W/D)并观察肺组织病理学特点,ELISA法检测肺组织中TNF-α和IL-35的含量,免疫组化法检测肺组织中总p38-MAPK蛋白和磷酸化p38-MAPK蛋白的表达。第二部分:45只7日龄新生SD大鼠,,同样分为A组、B组、C组,每组15只,造模后将幼鼠放入笼子与母鼠共同喂养,观察各组大鼠行为活动的改变并计算24小时存活率。结果:第一部分:相对比A组,B组肺组织病理学损伤严重,肺组织中TNF-α含量高而IL-35的含量低(P0.05),p38-MAPK蛋白和磷酸化p38-MAPK蛋白均呈强阳性表达。C组肺组织病理学损伤稍有改善,p38-MAPK蛋白和磷酸化p38-MAPK蛋白表达较弱,肺组织中TNF-α含量较急性肺损伤组低而IL-35的含量较高(P0.05)。第二部分:腹腔注射内毒素后2小时,B组大鼠开始出现活动减少、呼吸加速的现象,造模后6小时,B组大鼠开始出现呼吸急促、口唇发紫的现象,甚至有些新生大鼠咳出粉红色泡沫痰并出现紫绀的现象;C组大鼠症状较B组大鼠轻;A组活动、进食、反应正常,未出现上述症状。A组、B组、C组24小时存活率分别为100%、66.7%、86.7%。结论:盐酸戊乙奎醚预先给药有明显的肺保护作用,其机制可能与抑制p38-MAPK通路从而减轻大鼠急性肺损伤相关。
[Abstract]:Aim: to observe the effect of pentanethaquine hydrochloride pretreatment on the expression of p38 mitogen-activated protein kinase p38-MAPK in acute lung injury induced by lipopolysaccharide (LPS) in rats, and to explore the protective mechanism of pentenehyclidine hydrochloride on the lung of rats with acute lung injury induced by lipopolysaccharide (LPS). Methods: p38 mitogen-activated protein kinase p38-MAPK was detected in rats with acute lung injury induced by lipopolysaccharide (LPS). Methods: the experiment was divided into two parts. Part one: 30 7 day-old SD rats weighing 16 to 22 g. Three groups were randomly divided into three groups: normal saline group (n = 10), endotoxin group (n = 5), endotoxin group B (n = 5), penehyclidine hydrochloride group C group (n = 3) and group A (n = 5). The acute lung injury model was induced by intraperitoneal injection of endotoxin of 5 mg / kg and saline dilution to 5 ml in group A. Group C was injected intraperitoneally with penehyclidine hydrochloride (2mg / kg) and saline (5ml) 30 minutes before intraperitoneal injection of endotoxin. Lung tissue wet / dry weight ratio (WR) was measured and lung histopathological characteristics were observed. The contents of TNF- 伪 and IL-35 in lung tissue were detected by Elisa. The expression of total p38-MAPK protein and phosphorylated p38-MAPK protein in lung tissue was detected by immunohistochemical method. Part two: 45 7-day-old Sprague-Dawley rats were divided into two groups: group A (n = 15) and group B (n = 15). Results: the first part: compared with group A, group B had severe lung histopathological injury. In group C, the expression of p38-MAPK protein and phosphorylated p38-MAPK protein were slightly improved by pathological injury of lung tissue, and the expression of p38-MAPK protein and phosphorylated p38-MAPK protein was weak. The content of TNF- 伪 in lung tissue was lower than that in acute lung injury group, but the content of IL-35 was higher than that in acute lung injury group. Six hours after modeling, the rats in group B began to appear the phenomenon of shortness of breath, purplish lips, and even some newborn rats coughed up pink foam sputum and cyanosis. The symptoms of group C rats were lighter than those of group B rats. The 24-hour survival rate of group B and C was 100 and 66.7, respectively. Conclusion: Penehyclidine hydrochloride has obvious protective effect on lung, and its mechanism may be related to the inhibition of p38-MAPK pathway and the reduction of acute lung injury in rats. [WT5 "HZ] [WT5" BZ] [WT5 "BZ] [WT5" BZ] [WT5 "BZ] [WT5" BZ] [WT5 "BZ]
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614

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