DEX联合KTM对产后出血致多器官功能障碍大鼠IFN-γ和IL-4释放的作用

Dexmedetomidine combined ketamine reduced IFN-γ and IL-4 release in postpartum bleeding induced multiple organs dysfunction syndrome rats

目的观察右美托咪定(DEX)和氯胺酮(KTM)对产后出血致多器官功能障碍综合征大鼠IFN-γ和IL-4释放的影响。方法将80只产后24 h的SD大鼠随机分成4组(n=20):模型组(M组)进行失血性休克45 min+肠系膜上动脉夹闭40 min;右美托咪定组(DEX组)预注右美托咪定1μg/kg,持续注射右美托咪定4 h(2.5μg/kg/h),失血性休克45 min+肠系膜上动脉夹闭40 min;右美托咪定+氯胺酮组(DEX+KTM组)操作与DEX组完全相同,持续注射浓度为2.5μg/kg/h、1 mg/kg/h的DEX、KTM,维持4 h;对照组(C组)只进行麻醉,不进行任何操作。运用免疫组化技术检测造模后24 h大鼠免疫器官脾脏、肠系膜淋巴结、胸腺IFN-γ、IL-4的变化。结果脾脏、胸腺和肠系膜淋巴结均有IFN-γ和IL-4表达,M组、DEX组和DEX+KTM组脾脏、胸腺、肠系膜淋巴结IFN-γ、IL-4明显高于C组(P<0.05);DEX组和DEX+KTM组脾脏、胸腺、肠系膜淋巴结IFN-γ、IL-4明显低于M组(P<0.05);DEX+KTM组脾脏、胸腺、肠系膜淋巴结IFN-γ、IL-4明显低于DEX组(P<0.05)。结论右美托咪定联合氯胺酮能明显减少产后出血致多器官功能障碍综合征大鼠免疫器官炎症因子IL-4和IFN-γ的释放,比单纯应用右美托咪定或氯胺酮的效果更加明显,值得临床推广应用。

Objective To observe the effects of dexmedetomidine （DEX） combined ketamine （KTM） in reducing IFN-γ and IL-4 release in postpartum bleeding induced multiple organs dysfunction syndrome （MODS） rats. Methods 80 postpartum rats assigned randomly into four groups（n=20）. C group： The catheters placed in femoral artery and femoral vein and no other operation; M group： Based on C group, rats were induced hypotension for a period of 45 min and clamping of the superior mesenteric artery for a period of 40 min; DEX group： administration of DEX （2.5 μg/kg/h） for a period of 4 h to M group;DEX＋KTM group：administration of DEX＋KTM（2.5 μg/kg/h＋l mg/kg/h） for a period of 4 h to M group. All rats were killed 24 h at the end of experiment. Thymus, spleen, mesenteric lymph node tissue were collected for immunohistochemistry （IHC） measuring the expression of IFN-γ and IL-4. Results IFN-γ and IL-4 expression levels in thymus, spleen and mesenteric lymph nodes were higher in the MODS postpartum rats than those in control rats （P〈0.05）. IFN-γ and IL-4 expression levels were significant decreased in DEX/DEX＋KTM group when compared with those M group （P〈0.05）, and IFN-γ and IL-4 expression levels were lower in DEX＋KTM group than those in DEX group （P〈0.05）. Conclusion Dex combined KTM modulates IL-4 and IFN-γ expression in postpartum bleeding induced multiple organs dysfunction syndrome rats than DEX or KTM alone, indicating that Dex and KTM combined treatment may be better than single drug alone.