前列腺素E_1对急性肺损伤小鼠水通道蛋白1、5基因表达的影响

Effect of prostaglandin E_1 on expression of aquaporin 1 and aquaporin 5 mRNA in mice with actute injured lung

目的研究急性肺损伤(ALI)小鼠肺组织中水通道蛋白1(AQP1)、水通道蛋白5(AQP5)基因的表达变化,探讨前列腺素E(PGE1)治疗ALI的机制,为临床治疗ALI提供新的选择靶点和方法。方法 32只昆明小鼠随机分成4组(每组8只),即空白对照组(NS组)、造模组(ALI组)、前列腺素E1治疗组(PGE1组)、地塞米松治疗对照组(Dex组),观察6h后测定肺湿干重比值(W/D),并采用HE染色观察炎症变化,RTPCR检测AQP1mRNA、AQP5 mRNA、TNF-αmRNA、IL-1βmRNA的表达变化。结果 ALI组小鼠的肺部炎症反应显著,以中性粒细胞浸润为主,伴明显的肺泡充血、水肿。前列腺素E及地塞米松治疗后,肺组织炎症、充血明显改善,ALI组的W/D的比值与其他3组比较,差异有统计学意义(P均<0.05);与NS组相比,ALI组AQP1mRNA的表达显著降低(P<0.05),而PGE1组、Dex组的AQP1 mRNA的表达显著高于ALI组(P<0.05)。AQP5 mRNA表达的变化与AQP1mRNA的变化相似。与NS组相比,ALI组TNF-αmRNA的表达显著升高(P<0.05),而PGE1组、Dex组的TNF-αmRNA的表达显著低于ALI组(P<0.05)。IL-1βmRNA表达的变化与TNF-αmRNA的变化相似,肺损伤炎症减轻。结论PGE1可通过上调AQP1、AQP5的表达减轻肺损伤时肺水肿。可能是通过抑制炎症因子TNF-α、IL-1β的表达实现的。

Objective To explore the mechanism of prostaglandin E1 （PGE1 ） in the treatment of acute lung injury（ALI） in rats in- duced by lipopolysaccharide by studying changes of expression of aquaporin 1 （ AQPI ） ,aquaporin 5 （ AQP5 ） mRNA, in order to provide a new clinical method to treat ALL Methods Thirty - two kunming - mice were randomly divided into 4 groups; a saline control group （NS） ,a LPS group（ALI） , a prostaglandin EL group（ PGE1 ）and a dexamathasone group（Dex）. Wet/dry mass ratio（W/D） were assayed and lung tissue histopathological changed were observed at six hours. AQP1 mRNA, AQP5 mRNA,TNF -αmRNA and IL - 1βmRNA were assayed by RT - PCR. Results Histological tissue showed that extensive lung inflammation were seen in the ALl group,which manifested by accumlation of significant numbers of neutrophils, accompanied by marked pulmonary edema and hemorrhage. Compared with other groups, the difference of the W/D mass ratio of ALI group was not signficant（P 〈 0. 05 ） ;Compared with NS group, AQPI mRNA expres- sion in ALl group decreased significantly （P 〈 0.05 ） , while AQP1 mRNA expression in PGEl and Dex groups were higher than that in ALl group. The expression of AQP5 mRNA was similar to that of AQP1 mRNA. Compared with NS group, TNF - αmRNA expression in ALl group increased significantly （ P 〈 0.05） , while TNF - αmRNA expression in PGE1 and Dex groups were lower than that in ALl group. The expression of IL - 1βmRNA was similar to that of TNF - ctmRNA. Conlusion PGE1 may have beneficial effects on ALl by regulating AQPI and AQP5 expression in the lungs of rats,which are related to the inhibition of IL- 1βand TNF- α.