神经肽P物质对大鼠高氧肺损伤的保护作用

发布时间：2018-02-03 12:38

本文关键词： 高氧肺损伤神经肽P物质 pMAPK　出处：《第三军医大学学报》2014年06期 　论文类型：期刊论文

【摘要】：目的观察p38MAPK信号途径在高氧肺损伤中的表达,探讨神经肽P物质(substance P,SP)在高氧肺损伤中的保护作用及机制。方法将32只早产Sprague-Dawley大鼠按随机数字表法分配给代母鼠并分为4组,每组8只:正常对照组、空气加SP组、高氧加9 g/L盐水组、高氧加SP组。空气加SP组和高氧加SP组动物每天予腹腔注射SP 1×10-6mol·L-1·kg-1,正常对照组和高氧加9 g/L盐水组腹腔注射同等体积的9 g/L盐水。实验7 d后,观察肺组织病理改变;测定肺湿/干质量值(W/D)及肺组织中SP的含量;检测PCNA观察肺组织细胞的凋亡情况;采用免疫组化法检测p38在肺组织中的分布;蛋白免疫印迹法检测p38MAPK蛋白含量。结果与正常对照组相比,高氧各组均有不同程度的肺损伤,但SP干预组肺损伤较高氧加9 g/L盐水组有所减轻。肺W/D在第3、7天高氧肺损伤组明显高于正常对照组,高氧加SP组比高氧加9 g/L盐水组肺W/D在第7天显著降低。空气加SP组和高氧加SP组肺组织中的SP含量与正常对照组相比显著升高。免疫组化显示,高氧加9 g/L盐水组p38阳性表达较正常对照组明显增强;SP干预后p38MAPK阳性细胞较高氧加9 g/L盐水组明显减少。蛋白免疫印迹法显示,高氧加9 g/L盐水组p38MAPK含量明显高于正常对照组,干预后高氧加SP组p38MAPK含量低于高氧加9 g/L盐水组。各组肺W/D值、PCNA组织分布表达与p38MAPK蛋白含量变化趋势一致。结论高氧应激可激活损伤肺组织p38MAPK活性,SP对高氧肺损伤保护作用机制可能是通过下调高氧诱导的p38MAPK的激活实现的。
[Abstract]:Objective to observe the expression of p38 MAPK signal pathway in hyperoxia lung injury and to explore substance P of neuropeptide substance P (NPP). Methods 32 preterm Sprague-Dawley rats were randomly assigned to maternal rats and divided into 4 groups. There were 8 rats in each group: normal control group, air plus SP group, hyperoxia + 9 g / L saline group. Rats in the hyperoxia plus SP group and the air plus SP group and the hyperoxia plus SP group were intraperitoneally injected with SP 1 脳 10 -6 mol 路L -1 路kg-1 daily. Normal control group and hyperoxia + 9 g / L saline group were injected intraperitoneally with the same volume of 9 g / L saline. Lung wet / dry weight value (WR / D) and SP content in lung tissue were measured. PCNA was detected to observe the apoptosis of lung tissue cells. The distribution of p38 in lung tissue was detected by immunohistochemical method. The p38 MAPK protein content was detected by Western blot. Results compared with the normal control group, hyperoxia groups had different degrees of lung injury. However, the lung injury in SP intervention group was less than that in hyperoxia + 9 g / L saline group, and the lung WR / D was significantly higher in hyperoxia lung injury group than that in normal control group on the 7th day. Hyperoxia + SP group vs hyperoxia + 9. Lung W / D in g / L saline group decreased significantly on the 7th day. The SP content in lung tissue of air plus SP group and hyperoxia plus SP group was significantly higher than that of normal control group. Immunohistochemical staining showed that the content of SP in lung tissue was significantly higher than that in control group. The positive expression of p38 in hyperoxia + 9 g / L saline group was significantly higher than that in normal control group. Compared with hyperoxia + 9 g / L saline group, p38 MAPK positive cells were significantly decreased after SP intervention. The content of p38 MAPK in hyperoxia + 9 g / L saline group was significantly higher than that in normal control group. After intervention, p38 MAPK content in hyperoxia + SP group was lower than that in hyperoxia + 9 g / L saline group. The distribution and expression of p38 MAPK in PCNA tissue were consistent with the change trend of p38 MAPK protein content. Conclusion Hyperoxia stress can activate p38 MAPK activity in injured lung tissue. The protective mechanism of SP against hyperoxia lung injury may be by down-regulating the activation of p38 MAPK induced by hyperoxia.
【作者单位】：遵义市第一人民医院儿科;重庆医科大学附属儿童医院儿童重症医学科;
【基金】：贵州省科学技术基金(黔科合J字[2011]2341号)~~
【分类号】：R563.8
【正文快照】： 高氧疗法是抢救早产儿呼吸衰竭最常用的措施,然而长时间持续吸入高浓度氧气后,肺组织中由于持续高氧,细胞产生大量活性氧(reactive oxygen species,ROS),导致细胞内氧化/抗氧化体系失去平衡[1-3],出现肺泡上皮受损,继而引起成纤维细胞增生、细胞外基质沉积,最终引起肺纤维化的

【参考文献】