褪黑素对危重新生儿免疫功能影响的研究

Effects of melatonin on immunologic function of critically ill newborn.

目的观察危重新生儿免疫功能的改变及褪黑素对危重新生儿免疫功能的影响。方法2005-10—2006-10重庆医科大学儿童医院对50例危重新生儿外周血单个核细胞(PBMC)体外分别经植物血凝素(PHA)及PHA加褪黑素(melatonin,MT)刺激,均培养1h及48h,培养1h后用EMSA法检测细胞中核因子-B寡聚核苷酸(NF-κB)的含量,培养48h后用ELISA法检测IL-4、IFN-γ及TNF-α的含量。25例正常新生儿PBMC为对照(加PHA)。结果与对照组相比,危重新生儿存在NF-κB活性增高及Th1及Th2平衡紊乱,IL-4及TNF-α显著升高,IFN-γ降低;对于危重新生儿,加褪黑素激素NF-κB活性及细胞因子TNF-α降低(P<0.01),但IL-4及IFN-γ无显著变化。结论危重新生儿存在Th1及Th2功能紊乱,Th2相对优势,且NF-κB信号转导通路参与了危重新生儿的发病。MT能通过NF-κB信号转导通路改善患儿的免疫功能,但对Th1及Th2无影响。

Objective To obsevere the immunologic function of critically ill newborn and to study the effects of MT on immunologic function of neonates with severe illness. Methods Blood from 50 critically ill newborn were drawn （ divided into 50 neonatal PHA group and 50 neonatal MT group ） and 25 healthy neonate controls （ only PHA group ） were assessed. After stimulation with PHA （ PHA group ） and PHA ＋ MT （ MT group ） respectively, and cultured in vitro for 1 hours,the levels of NF-κB of peripheral blood mononuclear cells （PBMC） were checked by EMSA; cultured in vitro for 48 hours, the levels Of IFN-γ,IL-4 and TNF-α in the supernatants of PBMC were detected by ELISA respectively. Results Compared with the control, NF-κB of the critically ill neonates were activated and the cytokine were disordered, IL-4 and TNF- α increased,but IFNγ decreased. As to the severe disease of newborn,the levels of NF-κB and TNF-α of MT group were statistically lower（ P 〈 0. 01 ）, while IFN-γ and IL-4 didn t change, compared with PHA group. Conclusion There is dysfunction of Th1/Th2 in newborn with critically illness;the Th2 function prevails over the Thl function;furthermore NF-κB activation involves in the process in infants with critical illness. MT can improve the immunologic function of critically ill newborn through NF-kappaB signal transduction pathway, but MT cant influence the Th1/Th2.