Changes Of Pathology, ATP Production Rate And ATP Synthase Activity In Hippocampal Cortex Of Neonatal Pigs After Hypoxic-ischemic Brain Damage

Objective: To study the changes of pathology, ATP production rate and ATP synthase activity in hippocampal cortex of neonatal pigs after hypoxic-ischemic brain damage (HIBD).Methods: Forty-eight piglets of one to three days old were randomly assigned to experimental group and control group. Sham operation was performed on the control group which was exposed to normal atmosphere. The experimental group was performed cerebral hypoxic-ischemia(HI) by ligating left common carotid artery and then exposing the group to 8% 02 and 92% N2. After two hours the experimental group was put into normal atmosphere. According to the normal atmosphere exposing time, the experimental group was divided into 0hr, 24hr, 48hr, 72hr, 96hr group and every group has eight newborn pigs. Left hippocampal cortex was taken out from each newborn pigs, then we examined changes in mitochondrial morphology, ATP production rate and ATP synthase hydrolysis activity during the different normal atmosphere exposing time. Results: 1. After HI 2 hours, there had been changes of swell, cristae broken down, degranule in mitochondria. After refusion 24 hours, these changes were the most outstanding. Then they began to restore increasingly. After refusion 96 hours, the mitochondrial morphology was almost normal. 2. After HI hours, ATP production rate (45.42 +1.98) had declined obviously compared with control group (49.48 + 3.20), which showed significantly statistic difference (P<0.05). After refusion 24hours, the decline was the most outstanding (60.28+4.43) with significantly statistic difference (P<0.05). Then it began to restore increasingly. After refusion 96 hours, ATP production rate (48.06 +2.72) almost rearched normal level without statistic difference compared with control group (P>0.05). 3. After HI 2 hours, ATP synthase hydrolysis activity (80.49+ 5.06) had declined obviously compared with control group (100.40+8.18), which showed significantly statistic difference (P<0.05). After refustion 24 hours, the decline was the most outstanding (60.28 +4.43) with significantly statistic difference (P<0.05). Then it began to restore increasingly. After refusion 96 hours, ATP synthase hydrolysis activity (99.50 + 8.07) almost reached normal level without statistic difference compared with control group (P>0.05). 4. Regression and correlation analysis were given to ATP production rate and ATP synthase hydrolysis activity. The result demonstrated a very powerful positive linear relationship between them (r=0.935, P<0.05)Conclusion: Firstly, in early period of HI, changes in mitochondrial morphology and decline in ATP production rate, ATP synthase activity play a key role in pathogenesis of HIBD. Therefore, HIBD should be treated early and the sooner the better, especially, during the period of refusion 24 hours is the key therapeutic time. When treating HIBD, we should protect actively mitochondria from HI and refusion damage and sustain the stability of ATP content in cell. Secondly, ATP synthase is the key enzyme of ATP production, so it will be a new idea of treating HIBD in future that we regulate ATP Production rate by controlling ATP synthase activity. At last, this experiment will provide us with theoretical basis for investigating the effect of a variety of intervention in HIBD in future.