摘要
目的:探讨PI3K/Akt和JAK2/STAT3信号转导通路在二氧化硫(SO2)抗肢体缺血再灌注(I/R)致急性肺损伤中的作用。方法:应用双大腿根部绑扎止血带复制大鼠双后肢缺血再灌注肺损伤模型。在再灌注前20 min腹腔注射Na2SO3/Na HSO3;在再灌注前1 h静脉注射Stattic或LY294002。应用TUNEL、ELISA、Western blot等方法检测细胞凋亡、细胞因子表达及相关信号通路蛋白表达的情况。结果:与对照组相比,I/R组的MDA及MPO含量、肺系数、细胞凋亡指数、细胞因子表达以及p-STAT3、p-Akt蛋白的水平均显著增高;当应用Na2SO3/Na HSO3后,上述反映肺损伤的各项指标均下降。Western blot检测结果显示I/R后,肺组织中p-STAT3和p-Akt蛋白的水平均明显增加。而应用Na2SO3/Na HSO3后,p-Akt蛋白的水平继续增加,但p-STAT3蛋白的水平却减少(P<0.05)。结论:JAK2/STAT3和PI3K/Akt信号通路都参与了SO2抗肢体缺血再灌注致急性肺损伤的作用。JAK2/STAT3通路的活化,能够使I/R损伤加重;相反,PI3K/Akt信号通路的活化,可以使I/R损伤减弱。此外,JAK2/STAT3和PI3K/Akt信号通路之间存在交互作用。
AIM： To investigate the role of PI3K/Akt and JAK2/STAT3 pathways in the protection of sultur dioxide （SO2 ） against limb ischemia/repeffusion （I/R）-induced acute lung injury （ALI） in rats. METHODS： ALI was induced by limb I/R in the SD rats. Na2SO3 （0. 54 mmol/kg, ip）/NaHSO3 （0. 18 mmol/kg, ip） as SO2 donor was injec- ted at 20 min before reperfusion. The inhibitors of JAK2/STAT3 and PI3K/Akt pathways, Stattic （3 mg/kg, iv） and LY294002 （40 mg/kg, iv）, respectively, were injected at 1 h before reperfusion. Peripheral blood and lung tissues were collected for determining the contents of the eytokines, the protein levels of the molecules related to the signaling pathways, apoptosis and histopathologic changes by EL]SA, TUNEL and Western blot. RESULTS： Compared with control group, the content of MDA, the activity of MPO, lung coefficient, apoptotic index, cytokine expression, and the protein levels of p- Akt and p-STAT3 in I/R group all increased significantly, and administration of Na2SO3/NaHSO3 attenuated the damage in the lung. Besides, the results of Western blot showed that the tat lung tissues expressed p-STAT3 protein and p-Akt pro- rein. After I/R, the protein levels of p-STAT3 and p-Akt were increased. After using NazSO3/NaHSO3 , p-Akt was in- creased, but p-STAT3 was decreased （P 〈 0. 05 ）. CONCLUSION： Both JAK2/STAT3 and PI3K/Akt pathways are like- ly involved in the protective effect of SO2 against limb I/R-induced ALI in rats. The activation of JAK2/STAT3 signaling pathway increases I/R injury. Reversely, the activation of PI3K/Akt signaling pathway reduces I/R injury. Besides, JAK2/STAT3 and PI3K/Akt signaling pathways may have crosstalk during I/R-induced ALI and JAK2/STAT3 pathway may have an impact on the P13K/Akt pathway.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2015年第11期2076-2082,共7页
Chinese Journal of Pathophysiology
基金
北京市自然科学基金资助项目(No.7152061)
