细胞因子对缺氧缺血性脑病患儿脑血流动力学的调节作用及其机制

The regulating effect of cytokines on cerebral hemodynamics in neonates with hypoxic-ischemic encephalopathy and its mechanism

目的研究细胞因子对缺氧缺血性脑病(HIE)患儿脑血流动力学的调节作用及其机制。方法HIE患儿与正常对照新生儿各40例,均于生后24h内检测白细胞介素-6(IL-6)、IL-8与肿瘤坏死因子-α(TNFα-)等细胞因子及内皮素-1(ET-1)、降钙素基因相关肽(cGRP)与C型利钠肽(CNP)等血管活性因子,并于取血后即刻使用脉冲多普勒超声检测患儿大脑中动脉血流动力学参数变化。结果HIE患儿血浆IL-6、IL-8降低,TNFα-升高,并且阻力指数(RI)与IL-6呈负相关(r=-0.61,P<0.01),与IL-8、TNFα-呈正相关(r=0.80、0.72,P均<0.01);IL-6与ET-1呈负相关(r=-0.54,P<0.01),与CNP、cGRP呈正相关(r=0.49、0.52,P均<0.01);而IL-8、TNFα-与ET-1呈正相关(r=0.61、0.72,P均<0.01),与CNP、cGRP均呈负相关(r=-0.51^-0.63,P<0.01)。结论新生儿窒息后血浆IL-6、IL-8与TNFα-等细胞因子可能通过调节ET-1、cGRP、CNP等血管活性因子的变化而发挥对脑血流的调节作用,从而参与HIE的发病机制。

Objective To explore the mechanisms of cytokines on cerebral hemodynamic regulation in neonates with hypoxic-ischemic encephalopathy （HIE）. Methods The levels of peripheral blood interleukin-6 （IL-6）, IL-8, tumor necrosis factor-alpha （TNF-α）, endothelin-1 （ ET-1 ）, calcitonin gene-related peptide （cGRP）, C-type natriuretic peptide（CNP） in 40 HIE and 40 healthy neonates were detected on 1st day after birth using radioimmunoassay. Hemodynamic parameters of middle cerebral artery including peak systolic flow velocity （PSFV）, end-diastolic flow velocity （EDFV）, time-average mean velocity （TMFV）, pulsatility index （PI） and resistance index（RI） in two groups were measured by pulse Doppler ultrasound after the blood sam- pies were collected immediately. Results In HIE group plasma rlevels of TNF-α increased, while plasma levels of IL-6 and IL-8 decreased, which were correlated with disturbed cerebral hemodynamies and the changes of plasma levels of ET-1, cGRP, and CNP. Linear correlation analysis showed RI was negatively correlated with IL-6 level （ r = - 0.61, P 〈 0.01）, and positively correlated with IL-8 and TNF-α （ r = 0,80,0.72, P 〈 0.01）. Furthermore, IL-6 had negative correlation with ET-1 （ r = - 0.54, P 〈 0.01）, and positive correla- tion with CNP and cGRP （ r = 0.49,0.52, P 〈 0.01）. While IL-8 and TNF-α were positively correlated with ET- 1 （ r = 0.61,0.72, P 〈 0.01） and negatively correlated with CNP and cGRP （ r = - 0.51- -0.63, P 〈 0.01）. Conclusion The changes of plasma levels of IL-6, IL-8, and TNF-α inneonates with HIE may regulate cerebral hemodynamics by modulating the changes of ET-1, cGRP, and CNP so as to exerting an important role on the pathophysiologic mechanisms of HIE.