| Objectives:Many patients after successful cardiopulmonary resuscitation (CPR) were threatened to poor long-term outcome due to delayed cerebral damage of different levels. It was suggested that neuronal ischemia-reperfusions injury was related to brain damage after CPR, which represented an important factor leading to death for cardiac arrest (CA) patients. Reactive oxygen species (ROS) is one of current approved mechanism about ischemia-reperfusion injury, which has been a research focus in the resuscitation field in recent years. Tea polyphenols (TP) is found in the leaves of the green tea. Being a kind of antioxidants, TP contains many phenolic groups, so it can effectively inhibit oxygen free radicals, reduce lipid peroxidation and decrease oxidative stress level by various pathways. Previous studies demonstrated that TP could improve outcome in focal cerebral ischemia-reperfusion models, however it was rarely reported that TP could also enable neurons to benefit from systemic ischemia-reperfusion injury due to CA/CPR. This experiment was to observe the impact of TP on long-term survival and neurological function in the CA/CPR rats. The superoxide dismutase (SOD), malondialdehyde (MDA), hippocampal neuron damage and apoptosis after resuscitation were also observed. Therefore, this study was to explore whether TP could reduce the brain injury of CA/CPR rats by the antioxidant mechanism, which might provide new ideas for clinical work.Methods:1.98healthy Sprague Dawley rats were assigned at random to sham control group (n=14), saline group (CPR+saline n=42) and TP group (CPR+TP n=42). The saline group and TP group were anesthetized, intubated, and induced to CA by trans-esophageal cardiac pacing. They were given with intravenous fluid infusion of TP10mg/kg and saline2ml/kg as soon as restoration of spontaneous circulation (ROSC). And then they were kept in cages with vascular ligation after one hour of hemodynamic changes observation. The sham control group was anesthetized, intubated, and monitored the blood pressure, but was not induced to CA. Then they were kept in cages with vascular ligation after one hour of hemodynamic changes observation. The survival rate and neurological deficit score were recorded at different time points (12h,24h,48h,72h) and the total survival time was recorded.2.72healthy Sprague Dawley rats were assigned at random to sham control group (n=24), saline group (CPR+saline n=24) and TP group (CPR+TP n=24). The rats in each group were further subdivided into four groups according to four survival time-point (12h,24h,48h,72h), therefore, there were6rats in each group. The rats were induced to CA, given CPR and drug as the procedure in the first part. Their blood and hippocampus of all the rats that survived were taken out after ROSC (12h,24h,48h,72h) as designed, which were used to determine the SOD activity and MDA content. All the rats’ pathological changes by HE staining at different time points (12h,24h,48h,72h) and cell apoptosis by terminal deoxynucleotidy transferase-mediated dUTP nick end labeling (TUNEL) method in the hippocampal region at48hour point after ROSC were observed, and then apoptotic index(AI) were calculated.Results:1. After25min of restoration of spontaneous circulation (ROSC), the mean arterial pressure of the TP group was significantly higher than the saline group(P <0.01). The TP group had longer survival time compared to the saline group (23.5(18.5-41.5) vs19.25(7-29),(hour), P<0.01). The survival rate of the TP group at12h,48h,72h points were significantly higher than the saline group (92.9%(39/42),54.8%(23/42),45.2%(19/42) vs69%(29/42),28.6%(12/42),23.8%(10/42), P<0.05), however, at24h point, the difference between these two groups were not significant. Neurological deficit scores at each time point demonstrated that the TP group was significantly higher than the saline group (54(51.5-56),60(54-62),66(63-66),68(66-68) vs58(52-60),64(62-66),68(65-70),72(72-74), P<0.05, P<0.01))。2. The MDA levels both in plasma and hippocampal tissue of TP group at each time point were much lower than the saline group (3.42±0.32and4.78±0.4vs3.88±0.25and5.42±0.48,4.12±0.46and5.52±0.49vs4.99±0.44and6.53±0.62,4.87±0.63and6.61±0.61vs6.47±0.54and8.87±1.07,4.34±0.55and5.12±0.61vs5.37±0.66and5.98±0.44,(nmol/mg prot), P<0.05, P<0.01)). The SOD activities in plasma and hippocampus tissue of the TP group were higher than the saline group at12h,24h, and48h time points (190.67±0.17and 183.45±9.24vs172.46±12.17and162.76±15.55,176.4±16.69and163.23±16.12vs153.39±13.11and138.14±18.5,152.4±19.19and140.72±15.79vs122.87±16.2and116.6±13.96,(U/mg prot), P<0.05, P<0.01). At72h time point, the SOD activity in hippocampus tissue of the TP group were higher than the saline group(173.67±15.34vs142.79±16.15,(U/mg prot), P<0.01), however it was not significant in plasma. The pathological changes in the hippocampal region of saline group at12h,24h and48h points were more significant than TP group, but they were not significant at72h time point. The amount of apoptotic cell in the hippocampal region at48h after ROSC of saline group was more significant than TP group. The apoptosis index of two groups was significantly different, which was (4.9±2.2)%in TP group and (27.1±11.9)%in saline group(P<0.01).Conclusion:1. TP administration ameliorated the neurological outcomes, had a prolong survival time and increased the survival rate in CA/CPR rats, which was improved recovery.2. TP administration could decrease the degree of injury and apoptosis in the hippocampal region in CA/CPR rats. Additionally, it could decrease the MDA levels and enhance the SOD activity. Therefore TP administration could reduce the brain injury and had protective effects on neurons in CA/CPR rats by the antioxidant mechanism. |
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