| Objective: Hypoxic-ischemic encephalopathy (HIE) is a condition characterized by neurologic injury and symptom of cerebropathy caused by perinatal asphyxia. Recent the effective admitted pharmacological neuroprotection to prescribe for hypoxic-ischemic encephalopathy has not been formally addressed. Principal of un-pharmacotherapy is hypothermia.Therapeutic hypothermia is induced hypothermia lowers the core temperature of the brain by 2°C to 6°C for treatment. Recent a number of animal studies show that hypothermia is effective on neonatal animal brain.In terms of mechanisms of protective effect of hypothermia,studies have proposed that hypothermia might reduce energy consumption and anaerobic metabolism of cerebrum, reduce over- releasing and over- activation of extracellular excitotoxic amino acids, inhibit excessive accumulation of intracellular calcium,reduce production oxygen radical and NO,interfere inflammatory responses, attenuate cerebral edema and inhibit apoptosis.Recent investigation and experiment have shown that apoptosis of neurons and inflammatory over-activation play the significant role in the aggravated proceeding of HIE after hypoxic-ischemic(HI).Caspase-3,one of the most significant execute,which is called as cell killer, enzymolysis all or part of key proteinum the during apoptosis execution(activation or inactivation),is reported to play a crucial role. Caspase-3 is the imperative in developing cerebrum,and intimated correlation with acute injure as hypoxia ischemia and reperfusion. Hypoxic-ischemic encephalopathy is all accompanied with immunological reaction.The level of interleukin-18(IL-18)to increase is consequence of organism immunoreaction after hypoxia ischemia.This experiment was for the purpose of observing that treatment of neonatal hypoxic ischaemic encephalopathy with selective head cooling, observing concentration of caspase-3 and IL-18 during and after hypothermia, comprehending the neuroprotection mechanism of therapeutic hypothermia and providing the theory basis for clinical use of therapeutic hypothermia.Methods:1.Experiment objectsThe newborns of the intensive care unit in Hebei Province children hospital were selected, who entered newborn department on January, to December 2008, the embryo age exceed 37 weeks, the body weight exceed 2.5kilograms. HIE conformed to HIE diagnostic criteria in Diagnostic criteria for neonatal hypoxic-ischem ic encephalopathy in November 2004 by The Subspecialty Group of Neonatology, Pediatric Society, Chinese Medical Association.All infants were supplied with conventional therapy(sustain normal blood pressure and blood gas, sustain acid-base balance, confine fluid, control seizures, depress intracranial pressure and provid nutritional support, provid assisted respiration pro re nata).12 healthy full-term newborns borned in the same hospital in the same time were taken to the comparison group.2.The experiment groupsThe HIE infants were divided into the hypothermia group (Group A), and the conventional treatment comparison group (Group B), according to the random digits table, every group were divided into the moderate and severe, Group C for normal group.2.1 Group A of 16 examples, the average birth age 8.95±3.28hours,the embryo age 38.94±1.65weeks, the birth body weight3.34±0.46kg (19 examples were selected, to give up the treatment 1 example, to be rejected 1 example because of newborn scleredema, to be rejected because of sample haemolysis or absence 2examples);2.2 Group B 0f 16 examples, the average birth age 10.38±4.12 hours,the embryo age 39.14±1.67 weeks, the birth body weight 3.41±0.43 kg (21 examples were selected, to give up the treatment 3 example, to be rejected because of sample haemolysis or absence 2examples);2.3 Group C of 8 examples, the average birth age 10.04±4.14 hours,the embryo age 38.58±1.37 weeks, the birth body weight 3.20±0.51 kg, were selected randomly on the same time of the same hospital, who born in 12 hours, and were born in full-term, excepted for infection duration of pregnancy, congenital deformity, congenital metabolism dysfunction, intrauterine infection ,infection before or during delivery, severe intracranial hemorrhage, fracture of skull.。3.Laboratory procedure3.1 Group A and Group B infants of selected accepted the conventional therapy, included providing adequate oxygen and glycose, sustaining normal blood pressure and blood gas, sustaining acid-base balance, confining fluid, controlling seizures, depressing intracranial pressure and providing nutritional support, providing assisted respiration pro re nata. Group A simultaneously accepted the selective head cooling with hypothermia treatment. The entire journey two groups of infants were observed vital sign in whole range. The body temperature, the breath, the blood pressure,the blood routine,the clotting mechanism, seizures,w whether or not scleredema ere observed too.3.2 Group A were taken the venous blood 2ml when the hypothermia treatment (0h) and 24 hours (24h), 72 hours (72h),10days(10d) after therapy. With the 3500r/min centrifugalization 10 minutes, blood serum were accepted and set spare to -70℃refrigerator preservation. Group B were taken the venous blood 2ml when the hospitalization (0h) and 24 hours (24h) ,72 hours (72h) , 10days(10d) after therapy. With the 3500r/min centrifugalization 10 minutes, blood serum were accepted and set spare to -70℃refrigerator preservation. Group C were taken 2ml venous blood when born (0h) and 24hours (24h) ,72 hours (72h) , 10days(10d) after born and separated blood serum too. The blood serum were put into -70℃refrigerator for preservation.4 The experimental technique:caspase-3 and IL-18 concentration were monitored before and after therapy. The Elisa method was used. The reagent kits for caspase-3 and IL-18 Elisa were provided by Adlitteram Diagnostic Laboratories Inc,USA. the examination step and the method carried on according to which the medicine kit showed.5 The statistical analysis SPSS13.0 statistics software was used to carry on statistics processing, P<0.05 had statistical significance.Results:1. There was no statistical difference among the three groups for gestational age, birth weight, postnatal age, delivery mode and sex distribution (P>0.05).2. Compare of the time of caspase-3 and IL-18 concentration of group A: The caspase-3 and IL-18 concentration at 24 hour was higher than the 0 hour, At 72 hour, The caspase-3 and IL-18 concentration showed the tendency of increasing, and achieved the peak.But at 10day, the caspase-3 and IL-18 concentration were cut down, there was significant statistical difference (P<0.05). 3. Compare of the time of caspase-3 and IL-18 concentration of group B: At 0hour,24 hour and 72 hour,,the caspase-3 and IL-18 concentration showed the tendency of increasing, and achieved the peak at 0hour. But at 10day, the caspase-3 and IL-18 concentration were cut down compared with 10day, there was significant statistical difference (P<0.05).4. Compare of the time of caspase-3 and IL-18 concentration of group B:there was no significantly statistical difference between them(P>0.05).5. Compare of caspase-3 and IL-18 concentration of group A, group B and group C: Compare with group C, caspase-3 and IL-18 concentration of group A and group B was higher than group C, and there was significant statistical difference (P<0.05). There was no significant difference of caspase-3 and IL-18 concentration between group A and group B at the 0 hour. With the time changed, at the 24hour,72hour and 10day, the caspase-3 and IL-18 of group A was lower than group B,the peak of caspase-3 and IL-18 of group A was lower than group B, and there was significant statistical difference (P<0.05).Conclusions:1. Hypothermia could inhibit activation of apoptotic pathways ,inhibit release of caspase-3, lessen fragmentation of DNA,and the last reduce apoptosis of neuron.2. Hypothermia can suppresse express of IL-18, inhibit proliferation of microglia, suppresse releasing of IL-18 after insult, inhibit over-activation of inflammatory,show function of inflammatory regulations and neuroprotection, avoid aggravation of inflammatory and brain insult.3. Selective head cooling with hypothermia is effective neuroprotection on hypoxic ischaemic encephalopathy. |
PDF Full Text Request