丙戊酸钠对LPS诱导的急性呼吸窘迫综合征小鼠的治疗作用  

Therapeutic Effect of Valproic Acid on Lps-Induced Acute Respiratory Distress Syndrome in Mice

作　　者：刘跃辉[1] 裴红红[2] Liu Yuehui;Pei Honghong(The First Hospital of Yulin,Yulin,718000;The Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an,710004)

机构地区：[1]榆林市第一医院,榆林718000 [2]西安交通大学第二附属医院,西安710004

出　　处：《基因组学与应用生物学》2019年第7期3341-3345,共5页Genomics and Applied Biology

摘　　要：为了探讨丙戊酸钠(valproic acid,VPA)对急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)小鼠治疗作用及分子机制,本研究将30只雌性C57BL/6小鼠分为空白组、LPS组、LPS+VPA组,LPS+VPA组小鼠造模前腹腔预注射VPA,以LPS气管内注射诱导ARDS小鼠模型,6 h后检测各组小鼠肺水肿(湿重/干重),检测各组小鼠血液SOD和MDA水平;通过ELISA检测各组小鼠肺泡灌洗液中TNFα和IL-1β水平,Western blotting检测各组小鼠NF-κB p65和p-H2A.X蛋白表达水平。研究结果表明:与空白组相比,LPS组小鼠肺水肿显著升高,与LPS组比较,LPS+VPA组和阳性组小鼠肺水肿显著降低,差异具有统计学意义(p<0.01)。ELISA结果显示,与空白组比较,LPS组小鼠肺组织TNFα和IL-1β含量显著升高,与LPS组比较,LPS+VPA组小鼠肺组织TNFα和IL-1β含量显著降低,差异具有统计学意义(p<0.01)。与空白组比较,LPS组小鼠血液SOD活性显著降低,MDA含量显著升高,与LPS组比较,LPS+VPA组和阳性组小鼠血液SOD活性显著升高,MDA含量显著降低。Western blotting结果显示,与空白组比较,LPS组小鼠肺NF-κB p65和p-H2A.X蛋白表达显著升高,与LPS组比较,LPS+VPA组和阳性组小鼠肺NF-κB p65和p-H2A.X蛋白表达显著降低,差异具有统计学意义(p<0.01)。本研究初步表明:VPA能够抑制NF-κB通路,抑制小鼠氧化应激和炎症反应,保护ARDS小鼠肺组织。To investigate the therapeutic effect and molecular mechanism of Valproic acid(VPA)on acute respiratory distress syndrome(ARDS)mice,thirty female C57 BL/6 mice were divided into blank group,LPS group,LPS+VPA group.The mice in the LPS+VPA group were pre-injected with VPA before injection,and the ARDS mice model was induced by intratracheal injection of LPS.After 6 hours,the lung edema(wet weight/dry weight)of each group was detected.The levels of SOD and MDA in blood of each group were detected.The levels of TNFαand IL-1βin bronchoalveolar lavage fluid(BALF)of each group were detected by ELISA.The expression levels of NF-κB p65 and p-H2 A.X protein in each group were detected by Western blotting.Compared with the blank group,the lung edema of the LPS group was significantly increased.The results showed,compared with the LPS group,the lung edema of LPS+VPA group was significantly decreased,and the difference was statistically significant(p<0.01).Compared with the blank group,the blood SOD activity of the LPS group was significantly decreased,and the MDA content was significantly increased.Compared with the LPS group,the blood SOD activity of LPS+VPA group was significantly increased,and the MDA content was significantly decreased.The difference was statistically significant(p<0.01).The results of ELISA showed that the levels of TNFαand IL-1βin the BALF of the LPS group were significantly higher than those in the blank group.Compared with the LPS group,the levels of TNFαand IL-1βin the BALF of LPS+VPA group were significantly decreased,and the difference was statistically significant(p<0.01).Western blotting results showed that compared with the blank group,the expression of NF-κB p65 and p-H2A.X protein in the lung tissue of the LPS group was significantly increased.Compared with the LPS group,the expression of NF-κB p65 and p-H2A.X proteins in LPS+VPA group was significantly lower,and the difference was statistically significant(p<0.01).The preliminary results of this study show that VPA inhibits NF-κB p

关 键 词：丙戊酸钠 急性呼吸窘迫综合征 炎症 氧化应激 

分 类 号：R563.8[医药卫生—呼吸系统]