骨化三醇对脂多糖炎性大鼠神经保护作用的研究  

Neuroprotective effect of calcitriol in systemic inflammation induced by lipopolysaccharide

作　　者：李薇[1] 张申宁[1] 张仁良[1] 祁小平[2] 陈光辉[1] 

机构地区：[1]南京军区南京总医院神经内科,江苏南京210002 [2]南京军区南京总医院普通外科,江苏南京210002

出　　处：《医学研究生学报》2007年第2期155-159,I0006,共6页Journal of Medical Postgraduates

基　　金：南京军区南京总医院科研基金资助项目(批准号:2006014)

摘　　要：目的:观察骨化三醇对脂多糖(LPS)炎性大鼠脑组织的保护效应及作用机制。方法:健康雄性成年SD大鼠52只,随机分为三组:空白对照组6只、骨化三醇干预组23只[4μg/(kg.d)×14d]、脂肪乳剂(安慰剂)组23只[4ml/(kg.d)×14d],在第14d给药结束后1h,腹腔注射LPS 10mg/kg制造大鼠全身炎症模型,用凝胶电泳迁移率分析(EMSA)方法检测造模后3、6和9h脑组织核因子-κB(NF-κB),用ELISA方法测肿瘤坏死因子α(TN-α)、白细胞介素-10(IL-10),用苏木精-伊红(H-E)染色观察脑组织神经细胞损伤情况。结果:LPS腹腔注射使大鼠脑组织NF-κB活化、TNF-α表达增加,并随时间的延长而增高,伴有散在的大脑皮质浅表区神经元损害。骨化三醇干预能下调各时间点NFκ-B活性,降低TNF-α含量,并促进IL-10表达。骨化三醇干预减轻了神经细胞损伤程度。结论:大鼠腹腔注射LPS诱导的全身炎症状态能引发脑损伤,骨化三醇干预可能通过调节脑内炎性-抗炎因子的平衡而发挥神经保护作用。Objective ：To investigate neuroprotection of calcitriol in LPS-induced rat systemic inflammation and underlying mechanism. Methods：Aduh male Sprague-Dawley rats were randomized into three groups： blank group （6 rats ）, calcitriol group [23 rats, 4 ug/（kg · d） × 14d] and control group [23 rats, fat milk, 4 ml/（ kg · d） × 14 d]. 46 rats were induced systemic inflammation by intraperitoneal injection of LPS （ 10 mg/kg） on day 14 th, 1 hour after the administration. On post-injection 3,6,9 hour, 36 rats were anesthetized to death and obtained rat brain tissue to detect activity of NF-kB by EMSA and to assess TNF-α, IL-10 concentration by ELISA. HE staining was used to determine brain injury. Results ：LPS effectively activated NF-kB, enhanced TNF-α expression, induced sporadic neurons damage in brain in the control group and in time-dependent, compared with blank group rats. Calcitriol significantly down-regulated NF-kB activity, TNF-α expression but enhanced IL-10 expression at all time point evaluated, compared with the control group rats. Conclusion：Intraperitoneal injection of LPS can induce brain damage, Calcitriol modulate the inflammatory-antiinflammatory cytokine balance by downregulating activation of NF-KB, reducing over express of TNF-α and elevating IL-10 concentration.

关 键 词：脂多糖 骨化三醇 神经保护 

分 类 号：R741.02[医药卫生—神经病学与精神病学]