
头部亚低温对新生儿缺氧缺血性脑病半胱氨酸蛋白酶-3和白介素-18的影响
刘翠青, 夏耀方, 袁玉肖, 李莉, 邱向利
中国当代儿科杂志 ›› 2010, Vol. 12 ›› Issue (09) : 690-692.
头部亚低温对新生儿缺氧缺血性脑病半胱氨酸蛋白酶-3和白介素-18的影响
Effects of selective head cooling with mild hypothermia on serum levels of caspase-3 and IL-18 in neonates with hypoxic-ischemic encephalopathy
目的:探讨选择性头部亚低温治疗新生儿缺氧缺血性脑病(HIE)半胱氨酸蛋白酶-3(caspase-3)和白介素-18(IL-18)的变化,以了解头部亚低温治疗HIE的神经保护机制。方法:33例中、重度HIE患儿随机分为亚低温治疗组(n=16)和常规治疗组(n=17)。应用ELISA法检测0 h、24 h、48 h、72 h和5 d的外周血清中caspase-3和IL-18 的浓度。结果:亚低温组在治疗后24 h及48 h血浆caspase-3浓度分别为3.8±1.9和2.6±1.2 ng/mL,明显低于常规组的6.1±2.3和7.2±3.1 ng/mL,P<0.01。亚低温组血浆IL-8浓度在治疗后24 h、48 h及72 h亦出现明显下降,分别为119±30、76±33和71±40 ng/mL,与常规组的138±28、156±60和182±54 ng/mL相比,差异有统计学意义(P<0.01)。结论:应用头部亚低温治疗可抑制患儿血清中caspase-3和IL-18浓度的过度升高,揭示了头部亚低温治疗HIE的部分神经保护机制。[中国当代儿科杂志,2010,12(9):690-692]
OBJECTIVE: The study examined the changes of serum caspase-3 and IL-8 levels following selective head cooling with mild hypothermia (SHC) treatment in neonates with hypoxic-ischemic encephalopathy (HIE) in order to explore the mechanism of neuroprotection of SHC against HIE. METHODS: Thirty-three neonates with moderate or severe HIE were randomly assigned to two groups: SHC treatment (n=16)and conventional treatment (n=17). Serum levels of caspase-3 and IL-18 were measured using ELISA before treatment and 24 hrs, 48 hrs, 72 hrs and 5 days after treatment. RESULTS: Serum caspase-3 levels in the SHC group decreased 24 and 48 hrs after treatment (3.8±1.9 and 2.6±1.2 ng/mL, respectively) compared with 6.1±2.3 ng/mL at 24 hrs and 7.2±3.1 ng/mL at 48 hrs in the conventional treatment group (P<0.05). Serum IL18 levels in the SHC group decreased 24 hrs, 48 hrs and 72 hrs after treatment (119±30, 76±33 and 71±40 ng/mL, respectively) compared with those in the conventional treatment group (138±28 ng/mL at 24 hrs, 156±60 ng/mL at 48 hrs and 182±54 ng/mL at 72 hrs; P<0.01). CONCLUSIONS: SHC treatment can inhibit the release of caspase-3 and the expression of IL-18 in neonates with moderate or severe HIE. This may contribute to the neuroprotection of SHC against HIE.[Chin J Contemp Pediatr, 2010, 12 (9):690-692]
亚低温 / 缺氧缺血性脑病 / 半胱氨酸蛋白酶-3 / 白介素-18 / 新生儿
Mild hypothermia / Hypoxic-ischemic encephalopathy / Caspase-3 / IL-18 / Neonate
[1]Gluckman P, Wyatt J, Azzopardi D, Ballard R, Edwards A, Ferrieroet D, et al.Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial[J]. Lancet, 2005, 365(9460):663-670.
[2]中华医学会儿科学分会新生儿学组,新生儿缺氧缺血性脑病诊断标准[J].中国当代儿科杂志, 2005, 7(1):97-98.
[3]Northington FJ, Graham EM, Martin LJ.Apoptosis in perinatal hypoxic-ischemic brain injury: how important is it and should it be inhibited?[J].Brain Res Rev, 2005, 50(2):244-257.
[4]Rami A, Jansen S, Giesser I, Winckler J. Post-ischemic activation of caspase-3 in the rat hippocampus:evidence of an axonal and dendritic localisation[J]. J Neurochem Int, 2003, 43(3):211-223.
[5]Zhu C, Wang X, Hagberg H, Blomgren K. Correlation between caspase-3 activation and three different markers of DNA damage in neonatal cerebral hypoxia-ischemia[J]. J Neurochem, 2000, 75(2):819-829.
[6]Xu L, Yenari A, Steinberg K, Giffa G. Mild hypothermia reduces apoptosis of mouse neurons in vitro early in the cascade[J].Cereb Blood Flow Metab, 2002, 22(1): 21-28.
[7]Galasso JM, Liu Y, Szaflarski J, Warren S, Silverstein S. Monocyte chemoattractant piotein-1 is a mediator of acute excitotoxic injury in neonatal rat brain[J]. Neuroscience, 2000, 101(3):737-744.
[8]Hedtj-rn M, Leverin AL, Eriksson K, Blomgren K, Mallard C, Hagberg H. Interleukin-18 involvement in hypoxic-ischemic brain injury[J]. J Neurosci, 2002, 22(14): 5910-5919.
[9]Si QS, Nakamura Y, Kataoka K. Hypothermic suppression of microglial activation in culture:inhibition of cell proliferation and production of nitric oxide and superoxide[J]. Neuroscience, 1997, 81(1):223-229.
[10]Gunn AJ, Thoresen M. Hypothermic neuroprotection[J].NeuroRx, 2006, 3(2): 154-169.