大剂量地塞米松降低缺氧缺血性新生大鼠脑MCP-1蛋白表达

High Dose Dexamethasone Reduces the Expression of MCP-1 Protein in the Brain of Neonatal Rats with Hypoxia-ischemia

摘要:

目的 研究新生大鼠缺氧缺血性脑病 (HIE)时脑组织单核细胞趋化蛋白 - 1(MCP - 1)的表达及地塞米松对其影响。方法 2 5只新生大鼠分为 3组 :HIE模型对照组 (对照组 ) ,大剂量地塞米松治疗组 (大剂量组 ) ,小剂量地塞米松治疗组 (小剂量组 ) ;于造模后腹腔内分别注射生理盐水 10ml/kg ,地塞米松 10mg/kg及地塞米松 0 .5mg/kg ;2 4h后处死后取脑组织 ,免疫组化法检查脑组织MCP - 1蛋白的表达 ,光镜检查脑病理改变情况。结果 对照组、大剂量组、小剂量组的MCP - 1蛋白 ,神经细胞总数及变性 /坏死神经细胞数 ,分别为 7.98±1.37% ,0 .97± 0 .42 % ,7.2 5± 2 .45 % ;15 8.0 7± 14.48个 / 6HP ,2 0 3.2 5± 10 .2 7个 / 6HP ,15 5 .11± 16 .6 1个 / 6HP ,2 2 .86± 3.13个 / 6HP ,17.75± 3.45个 / 6HP ,2 3.89± 4.18个 / 6HP。与对照组相比 ,大剂量组MCP - 1蛋白表达减少 (P <0 .0 1) ,神经细胞总数增加 (P <0 .0 5 )及变性 /坏死神经细胞数减少 (P <0 .0 1) ,而小剂量组改变不明显(P >0 .0 5 )。结论 大剂量地塞米松可能通过降低HIE脑组织中MCP - 1蛋白表达对HIE脑组织损伤产生保护作用。

Abstract:

Objective To investigate the expression of Monocyte Chemoattractant Protein-1 (MCP-1) in the brain of neonatal rats subjected to hypoxia ischemia and the influence of different doses of dexamethasone on the expression of MCP-1 protein and neuropathology. Methods Using a hypoxic ischemic neonatal rat model (n=25), animals received intraperitoneal injections of normal saline (control group), and 0.5 mg/kg and 10 mg/kg of dexamethasone immediately after the hypoxic injury. All animals were killed 24 hours after hypoxia. Immunocytochemistry with a polyclonal goat antirat MCP 1 antibody was used to determine the expression of MPC 1 protein. Total and percentage denatured (necrotic) neurons were determined using light microscopy. Results In the control group, the expression of MCP 1 protein and the total number of neurocytes and denatured (necrotic) neurons were 7.98 ± 1.37% , 158.07 ± 14.48 /6HP and 22.86 ± 3.13 /6HP, respectively, while in the high dose group, they were 0.97 ± 0.42% , 203.25 ± 10.27 /6HP and 17.75 ± 3.45 /6HP, respectively. And in the low dose group, they were 7.25± 2.45% , 155.11 ± 16.61 /6HP and 23.89 ± 4.18 /6HP, respectively. Compared to the control group, the expression of MCP 1 protein was significantly decreased (P< 0.01 ),the total number of neurons increased (P< 0.05 ), and denatured (necrotic) neurons decreased (P<0.01) in the high dose groups, but there were no major histopathological differences between the low dose group and the control group. Conclusions High dose dexamethasone treatment reduces the expression of MCP-1 protein in the brain of neonatal rats with hypoxic ischemic encephalopathy, and might have a neuroprotective role in this disorder. [