CAJ | 학술논문

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Na2 SO3／NaHSO3；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Na2 SO3／NaHSO3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Na2 SO3／NaHSO3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。
목적：탐토PI3K／Akt화JAK2／STAT3신호전도통로재이양화류（SO2）항지체결혈재관주（I／R）치급성폐손상중적작용。방법：응용쌍대퇴근부방찰지혈대복제대서쌍후지결혈재관주폐손상모형。재재관주전20 min복강주사Na2 SO3／NaHSO3；재재관주전1 h정맥주사Stattic혹LY294002。응용TUNEL、ELISA、Western blot등방법검측세포조망、세포인자표체급상관신호통로단백표체적정황。결과：여대조조상비， I／R조적MDA급MPO함량、폐계수、세포조망지수、세포인자표체이급p－STAT3、p－Akt단백적수평균현저증고；당응용Na2 SO3／NaHSO3후，상술반영폐손상적각항지표균하강。 Western blot검측결과현시I／R후，폐조직중p－STAT3화p－Akt단백적수평균명현증가。이응용Na2 SO3／NaHSO3후， p－Akt단백적수평계속증가，단 p－STAT3단백적수평각감소（P＜0．05）。결론： JAK2／STAT3화PI3K／Akt 신호통로도삼여료SO2항지체결혈재관주치급성폐손상적작용。JAK2／STAT3통로적활화，능구사I／R손상가중；상반，PI3K／Akt신호통로적활화，가이사I／R손상감약。차외， JAK2／STAT3화PI3K／Akt신호통로지간존재교호작용。
AIM:To investigate the role of PI3K/Akt and JAK2/STAT3 pathways in the protection of sulfur dioxide (SO2) against limb ischemia/reperfusion (I/R)-induced acute lung injury (ALI) in rats.METHODS:ALI was induced by limb I/R in the SD rats.Na2 SO3 (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 cytokines, the protein levels of the molecules related to the signaling pathways, apoptosis and histopathologic changes by ELISA, 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 Na2 SO3/NaHSO3 attenuated the damage in the lung.Besides, the results of Western blot showed that the rat lung tissues expressed p-STAT3 protein and p-Akt pro-tein.After I/R, the protein levels of p-STAT3 and p-Akt were increased.After using Na2 SO3/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.