临床儿科杂志 ›› 2014, Vol. 32 ›› Issue (5): 480-484.

• 实验研究 • 上一篇    下一篇

褪黑素对新生大鼠缺氧缺血后脑中galectin-3、TNF-α、IL-1β水平变化及长期行为能力的影响

乔丽丽,沈伟勤   

  1. 上海市松江区中心医院儿科(上海 201600)
  • 收稿日期:2013-08-11 出版日期:2014-05-15 发布日期:2014-05-15

The effect of melatonin on galectin-3, TNF-α, and IL-1β in newborn rats brain damage after hypoxia-ischemia and its impact on long-term behavior 

QIAO Lili, SHEN Weiqin    

  1. (The Department of pediatrics, Songjiang Central hospital, Shanghai, China)
  • Received:2013-08-11 Online:2014-05-15 Published:2014-05-15

摘要:

 目的 探讨褪黑素对新生大鼠缺氧缺血性脑损伤(HIBD)的保护作用及其机制。方法 72只5日龄Wistar大鼠随机分成生理盐水(NS)组、褪黑素组、缺氧缺血+生理盐水(HINS)组、缺氧缺血(HI)褪黑素组。各组大鼠分别在HIBD后24 h、72 h、7周处死,取脑经免疫组化染色计数半乳糖凝集素-3(galectin-3)细胞,酶联免疫吸附法测肿瘤坏死因子(TNF)-α和白介素(IL)-1β蛋白水平。HIBD后7周以恐惧测试(fear condition test)和高空十字架测试(elevated plus maze test)评估大鼠记忆能力和抗焦虑能力。结果 HIBD后72 h、7周时,HI褪黑素组皮质区的galectin-3 阳性细胞数明显少于HINS组,差异有统计学意义(P<0.05)。HIBD后24 h、72 h,HI褪黑色素组的TNF-α和IL-1β蛋白表达水平均低于HINS组,差异均有统计学意义(P<0.05)。恐惧测试中,在声音刺激前HI褪黑素组与HINS组的差异无统计学意义(P>0.05);在声音刺激后,HI褪黑素组的恐惧百分数高于HINS组,差异有统计学意义(P<0.05)。高空十字架测试中HI褪黑素组进入开放臂的次数和停留时间百分数均少于HINS组,差异有统计学意义(P<0.05)。结论 褪黑素对HIBD后大脑损伤有短期和长期的保护作用。

Abstract:  Objectives To investigate neuroprotective effect of melatonin on preterm rats brain damage after hypoxia-ischemia (HI). Methods In this study, 5-day-old Wistar rats were divided into four groups: Normal saline ()group, melatonin group, HI+NS group and HI+melatonin group. HI was conducted by unilateral ligation of the left common carotid artery (ischemia) and 50 min of hypoxia. Melatonin was injected at a dose of 5mg/kg intraperitoneally three times: before ischemia, after hypoxia and 24 h after the second dose. The pups were sacrificed at 24 h, 72 h, and 7 w after HI; for galectin-3 cells count at 72 h and 7 w; TNF-α, IL-1β protein were measured in 24 h and 72 h after HI; and fear condition and elevated plus maze were tested in 7 w after HI. Results The number of galectin-3- positive cells was lower after melatonin treatment than vehicle treatment in 72 h and 7 w after HI (all P<0.05). TNF-α protein and IL-1β protein both increased at 24 h and 72 h after HI, and reduced after melatonin treatment (all P<0.05). Melatonin treatment improved memory ability and learning ability, reduced anxiety in 7 w after HI. Conclusion Melatonin has long-term and short-term protective effect on developing brain damage after HI.