Dynamic Detection And Clinical Significance Of IL-6and NF-κB Of Serum In Premature With White Matter Damage

Objective: Premature is the neonate who is less than37weeks. Alongwith the rapid development of the obstetric and neonatal diagnosis andtreatment technology, more and more premature can be survival, but theincidence of white matter damage in premature also increase significantly.Later in the white matter damage it can lead to cerebral palsy,epilepsy,mentalretardation,behavior anomaly and barrier of hearing,vision and the language,all this make the children life quality drop, aggravating the family and socialburden. According to the new statistics,10percent to30percent prematurehave neurologic sequelae or mental disorders in different degrees[1]. Therefore,to prevent and intervene white matter damage is a hot spot in the clinical andsocial problems.The two of the most common pathological type in white matter damage isintraventricular hemorrhage(IVH) and periventricular leukomalacia(PVL), it isthe main cause of mental retardation and cerebral palsy[2-5]. The mechanism ofwhite matter damage in premature has not been fully elucidated onset, themain interpretation is cerebral vascular development and automatic adjustmentfunction of cerebral blood flow. In recent years epidemiological and animalstudies confirmed that intrauterine infection/inflammatory reaction plays a keyrole in the PVL. Animal experiment through to pregnant mice which LPS isinjected, can successfully establish the cerebral white matter damage model ofpalace infection/inflammatory reaction, and find that the model can activatethe fetal rat and mouse the Thl/Th2immune response, make IL-6,TNF-α rise[6].It fully illustrates that cytokine may be mediated the process of white matterdamage which caused by intrauterine infection.These interactions between cytokines lead to white matter damage inpremature ultimately, but the specific mechanism is still not fully clear. In recent years, cytokines especially nuclear factor and interleukin pay attentionto the release of inflammatory mediators in the mechanism of white matterdamage.NF-κB as a distribution and wide function of range of eukaryotic cellstranscription factors, it has been taken seriously in clinical disease research.The study proves that NF-κB is widespread in the central nervous system,andparticipate in the cerebral ischemia reperfusion and the pathological process ofwhite matter damage[7]. When the body is stimulused by hypoxia and ischemiastress, it can start a series process of inflammatory response and immunerelated genes transcription, induct the high expression of cytokines such asIL-6,IL-1,TNF-α et al. In recent years, cytokines especially IL-6pay atten-tion to the release of inflammatory mediators in the mechanism of Prematureencephalopathy. IL-6is one of the components in complicated cytokinesnetwork, it can combine with its receptor, identify signal transductioncomponents gpl30through the protein phosphorylation signaling pathways,then start the gene expression of a variety of cytokines, adhesion molecule,romote the proliferation of MG, result in the death of oligodendrocytes,influence the myelin formation of the central nervous system, aggravatingwhite matter damage. For IL-6in term of HIE, a lot, multi-angle researcheshave been done. It confirm that the level of IL-6decreases gradually withcourse of HIE, and in acute phase the level of IL-6and the CT value wasnegatively correlated[8]. In addition,combining with NBNA score, we foundthat the score is lower, the greater the brain damage[9].Whether nuclear factor and cytokine play a role in white matter damagethrough the release of inflammatory mediators or not, we do not know.Therefore, this experiment is to detect serum level of IL-6, NF-κB in normalpremature and premature with white matter damage born3rdand10thdays, toinvestigate the role of cytokine in the mechanism of action, provides a newway for prevention and intervention of white matter damage.Methods: From2011September to2012September in neonatology ofHandan maternity and child care centers, fifty premature cases were selectedfrom, who’s the gestational age28-35weeks and weight is1000g-2500g. According to the result of their brain MRI, they are divided into a controlgroup of normal premature and premature with cerebral white matter damagegroup. Normal control group included20cases of premature infants. In linewith their severity, premature with cerebral white matter damage group aredivided into: mild to moderate group and severe group. The diagnosis andgrouping situation of white matter damage as follows.mild to moderate groupwere20cases; severe group contained10cases; There are no statisticallysignificant differences in gestational age, birth weight, gender of each group,P>0.05.All parents agreed with the collection of specimen.Blood of peripheral vein were collected and obtained serum by centrifugefrom50preterm who were born third and10thdays. The levels of serum IL-6and NF-κB were ditected by enzyme-linked immunosorbent assay (ELISA).Combined with comparative analysis of relevant clinical data, a statisticaltreatment was performed.Result:1The change of serum IL-6levels of premature born3rddays in threegroupsSerum IL-6level of normal control group is lower than mild to moderategroup, severe group; Serum IL-6level of mild to moderate group is lower thansevere group, there is a statistically difference (P＜0.05).2The change of serum IL-6levels of premature born10thdays in threegroupsSerum IL-6level of mild to moderate group can compare with normalcontrol group, and there is little difference and not statistically significant(P>0.05); Serum IL-6level of severe group is higher than normal controlgroup and mild to moderate group, and there is a statistically difference (P＜0.05).3The change of serum IL-6levels of three group premature born3rdand10thdaysCompared with normal control group born3rddays, serum IL-6level ofnormal control group born10thdays has some decrease. However, there is little difference and not statistically significant (P>0.05). Compared with mildto moderate group born3rddays, serum IL-6level of mild to moderate groupborn10thdays has obvious decrease, and there is a statistically difference (P＜0.05). Compared with severe group born3rddays, serum IL-6level of severegroup born10thdays has obvious decrease, and there is a statisticallydifference (P＜0.05).4The change of serum NF-κB levels of premature born3rddays in threegroupsSerum NF-κB level of normal control group is lower than mild tomoderate group, severe group; Serum NF-κB level of mild to moderate groupis lower than severe group, there is a statistically difference (P＜0.05).5The change of serum NF-κB levels of premature born10thdays in threegroupsSerum NF-κB level of normal control group is lower than mild tomoderate group, severe group; Serum NF-κB level of mild to moderate groupis lower than severe group, there is a statistically difference (P＜0.05).6The change of serum NF-κB levels of three group premature born3rdand10thdaysCompared with normal control group born3rddays, serum NF-κB level ofnormal control group born10thdays, there is not statistically significant(P>0.05). Compared with mild to moderate group born3rddays, serum NF-κBlevel of mild to moderate group born10thdays has obvious decrease, and thereis a statistically difference (P＜0.05). Compared with severe group born3rddays, serum NF-κB level of severe group born10thdays has obvious decrease,and there is a statistically difference (P＜0.05).Conclusions:1Born3rddays, serum IL-6level of mild to moderate group and severegroup is significantly higher than control group, serum IL-6level of severegroup is significantly higher than mild to moderate group, it prompts that theactivation of IL-6is involved in the occurrence of white matter damage, andIL-6is closely relative to degree of pathological changes, so the monitoring of serum IL-6level for white matter damage which provides the basis for earlydiagnosis and intervention.2Born10thdays, serum IL-6level of mild to moderate group can comparewith control group, and there is no obvious difference. However serum IL-6level of severe group is higher than mild to moderate group and control group.It suggests that high level of serum IL-6can exist for a long time when severewhite matter damage, it still aggravate the white matter damage, so furtherattention and intervention should be pay attention to.3Born3rddays, serum NF-κB level of mild to moderate group and severegroup is significantly higher than control group, From the structure and signaltranscription path of NF–κB，we can speculate: the activation of NF-κB canrapidly induce the transcription of target gene, promote inflammation factorformation,such as IL-6, it can make large number of inflammatory cells linktogether and release more oxygen radical, all this play a role of cytotoxicity,aggravate white matter damage.4Born10thdays, serum NF-κB level of severe group compare with born3rddays, it decrease, but serum NF-κB level of severe group is higher thanserum NF-κB level of mild to moderate group and control group. Meanwhileserum NF-κB level of mild to moderate group is still higher than control group.It suggests that high level of serum NF-κB decrease more slowly, the generegulation of more inflammatory factors such as il-6last a long time, thusfurther aggravate the brain damage.