罗格列酮预处理减轻肠缺血再灌注损伤

Rosiglitazone Preconditioning Attenuate Intestinal Ischemia-reperfusion Injury

关键词:  罗格列酮  肠缺血再灌注损伤  炎症  JAK2/STAT3

Key words:  rosiglitazone  intestinal ischemia reperfusion injury  inflammation  JAK2/ STAT3

摘要:

目的 探讨罗格列酮(rosiglitazone，RGZ)对大鼠肠缺血再灌注损伤的作用及其机制。方法 30只SD大鼠，♂，随机分成假手术组、缺血再灌注损伤组(IRI组)和罗格列酮预处理组(RGZ组)。罗格列酮预处理组在手术前1 h静脉注射罗格列酮(0.3 mg·kg^-1)，假手术组和IRI组在手术前1 h静脉注射等量生理盐水。手术分离肠系膜上动脉，通过夹闭45 min、再灌注4 h诱导缺血再灌注损伤。PAS染色观察肠道黏膜病理学形态学变化，RT-PCR和ELISA检测白介素6(IL-6)、干扰素(IFN-γ)和肿瘤坏死因子(TNF-α)。Western blot检测PPAR-γ，p-PPAR-γ，JAK2，p-JAK2，STAT3和p-STAT3的表达。结果 与假手术组相比，IRI组肠黏膜损伤明显增加，ELISA和RT-PCR显示IL-6，IFN-γ和TNF-α也明显上调，Western blot检测结果显示，表达p-PPAR-γ，p-JAK2，p-STAT3明显增加，但PPAR-γ，JAK2和STAT3无明显变化。与IRI组相比，RGZ组小肠黏膜损伤明显减少、IL-6、IFN-γ和TNF-α表达降低，但p-PPAR-γ，p-JAK2和p-STAT3表达进一步增加，而PPAR-γ，JAK2和STAT3表达差异仍无统计学意义。结论 罗格列酮预处理可通过激活JAK2/STAT3信号通路抑制炎症反应，从而减轻肠缺血再灌注损伤。

Abstract:

OBJECTIVE To investigate the effect of rosiglitazone on intestinal ischemia reperfusion injury and its potential mechanism. METHODS Thirty rats were randomly divided into sham operation group, ischemia reperfusion injury group(IRI group) and IR plus rosiglitazone preconditioning group(RGZ group). RGZ group were administered by intravenous injection (0.3?mg·kg^-1) 60 min prior to operation in RGZ group, and the equal volume of saline was administered in the other 2 groups. The intestinal IR injury was induced in IRI group and RGZ group using bulldog clamps on superior mesenteric artery by 45 min of ischemia followed by 4 h of reperfusion. The pathology of intestinal tissues was observed according to PAS staining. The expression level of IL-6, TNF-α and IFN-γ were measured by PCR and ELISA. The expression of p-PPAR-γ, PPAR-γ, JAK2, p-JAK2, STAT3 and p-STAT3 were measured by Western blot. RESULTS Compared with the sham operation group, the level of mesenteric injuries in IRI group was significantly higher. Moreover, the expression level of IL-6, TNF-α, IFN-γ, p-PPAR-γ, p-JAK2 and p-STAT3 were all higher than the sham operation group, but the expression level of PPAR-γ, JAK2 and STAT3 had no difference. Compared with the IRI group, the level of mesenteric injuries, the expression level of IL-6, TNF-α and IFN-γ in the RGZ group were significantly reduced, but the expression of p-PPAR-γ, p-JAK2 and p-STAT3 were further increased and the expression level of PPAR-g, JAK2 and STAT3 still had no difference between IRI and RGZ groups. CONCLUSION Rosiglitazone preconditioning can protects rats against intestinal ischemia-reperfusion injury by activating JAK2/STAT3 signal pathway to attenuate inflammation.