Expression Of MiRNA In Plasma Of Moderate Or Severe Neonatal Hypoxic Ischemic Encephalopathy

Objective To screen the moderate or severe hypoxic ischemic encephalopathy(HIE)newborn associated micro RNAs,and analyze it's expression in different degree of multiple organ damage as well as before and after the treatment,to observe micro RNAs' clinical significance in diagnosis,treatment and prognosis of HIE combined multiple organ injury.Methods A total of 117 neonates with HIE,who were admitted to the Neonatal Intensive Care Unit of The second hospital of Jiaxing,from July 2013 to April2016,were divided into mild group(n=69),moderate or severe group(n=48)according to the conditions,48 neonates served as case group.30 healthy full term neonates were healthy controls.According to the diagnostic criteria of multiple organ dysfunction syndrome,the case group was further divided into three groups of one organ injury group,more than two organs injury group and no organ injury group.The expression profile of mi RNA in healthy controls and HIE group was examined using mi RNA chip,5 mi RNAs were chosen for further verification by realtime fluorescence quantitative Polymerase Chain Reaction(PCR).We then compared mi RNA expressions among these groups and analyzed the relationship between mi RNA expressions and diagnosis,treatment and prognosis of HIE.T tests and Chi-square tests and orthers were used for statistical analysis.Results Mi RNA microarray showed that there were 55 mi RNAs expressing differently in HIE group,29 mi RNAs were up-regulated while 26 mi RNAs were down-regulated.Through real-time PCR,three mi RNAs,mi R-4472,mi R-5195-3P and mi R-6794-5P are significantly up-regulated in moderate or severe HIE group contrast to healthy controls,and these three mi RNAs are lower than which before the treatment(all P < 0.05).In addition these mi RNAs were chosen for futher research in HIE group combined with organ injury,the result is the same as that.It revealed that the expression level of mir-4472,mir-5195-3p and mir-6794-5p in moderate or severe HIE group with organ injury was significantly increased(all P < 0.05),besides,the more organs injured,the greater difference in mi RNA expression profile it showed.We also found that there is obvious difference after treatment in these groups,expression level of mir-4472,mir-5195-3p and mir-6794-5p in moderate or severe HIE group with organ injury are up-regulated.And in moderate or severe HIE group combined viscera damage,the expression mi R-4472,mi R-5195-3p and mi R-6794-5p was decreased after successful treatment.Receiver operating characteristic curve showed that the area under the curve(AUC)of these 3 mi RNAs in moderate or severe HIE with MODS groups were 0.9294,0.9412,and 0.9118,respectively,all>0.9,the biggest is mi R-5195-3p.Conclusions Mi R-4472,mi R-5195-3p,mi R-6794-5p were obviously up-regulated in moderate or severe HIE group,also in moderate or severe HIE groups with organ injury.Mi R-4472,mi R-5195-3p and mi R-6794-5p are involved in the pathogenesis of HIE process,which can be used as a kind of biological marker of HIE combined multiple organ dysfunction syndrome,especially mi R-5195-3p.The detection of relevant mi RNAs is conductive to the diagnosis and treatment of HIE,we can predict the possible existence HIE with organ injury,for early intervention;Mi R-4472,mi R-5195-3p and mi R6794-5p may be new therapeutic targets in HIE.