| Objective:Ketamine is one of the most common intravenous anesthetics. The recent study demonstrated Ketamine induced the damage of the developing brain and resulted in the long-term cognitive dysfunction. Propofol is often used in induction and maintaining anesthesia. Several experiments showed Propofol has protective action to neuron, it is promising whether the combination of Propfol and Ketamine may reduce the toxicity of Ketamine and attenuate the long-term cognitive damage on the infant and children. Therefore, in this study, we employed the infant rat receiving anesthesia with different doses of Propfol or/and Ketamine to evaluate the effect of propofol on the hippocampal neurons and cognitive function injuries induced by ketamine anesthesia. Methods:Eighty SD infant rats(7 days post-birth) were divided randomly to NS group (saline), K group (Ketamine 70mg/kg), P group (Propfol 70mg/kg), K+P group (Ketamine 70mg/kg+ Propfol 70mg/kg)(n=20 per group).The medicine was intraperitoneally (i.p.) injected in a volume of 1ml/kg every two hours in a blind fashion respectively. 6h after first injection, the animals in each group were separated randomly to two groups:group A and group B. In group A, the rat was immediately sacrificed and hippocampus tissue was harvested for paraffin section and the neuron apoptosis as well as Bcl-2/Bax protein expression were determined. In group B, the cognitive function of the rats were detected with Morris water maze 3 weeks after anesthesia.Results:1. The apoptosis index (AI) of CA1 neuron in hippocampus in K group was 15.31±6.32%, which elevated significantly compared to that in NS group(3.89±2.97%, P＜0.01); The AI in P group was (5.62±4.89%),It missed the statistic difference from that in NS group (P>0.05). The AI in K+P group was 9.82±6.63%, which was significantly higher than that in NS group (P±0.05), while it was significantly lower compared to that in K group (P<0.05)2. The expression ratio of Bcl-2 protein in hippocampus CA1 neuron in NS group was 0.86±0.61%, which missed the statistical significance compared to that (1.95±1.75%) in K group (P>0.05); The ratio of P group was 9.75±4.03%, which increased significantly compared to that in NS group or in K group (Both P<0.01); The ratio of K+P group was 8.67±5.42%. It was elevated than that in NS group or K group (Both P±0.01),while there was no statistical significance between K+P group and P group.3. The expression ratio of Bax protein in hippocampus CA1 neuron in NS group was 1.09±0.65%, which was significantly lowered than that in K group (8.95±6.24%) (P<0.01); The ratio of Bax protein in P group was 3.83±2.17%, which was elevated significantly than that in NS group (P＜0.05); The ratio in K+P group was 8.26±4.17%, it increased significantly than that in NS group (P＜0.05),while it missed the statistical difference compared to that in K group (P>0.05)4. With the water maze test, the latency period of NS,P,K+P group in the 3rd day were significantly shorter than that in the 1st day (P<0.05), whereas no difference was found in K group. The latency period in the 3rd day in K,P,K+P group was significantly elevated than that in NS group, while the latency period in the 3rd day in P,K+P group was significantly shorter compared to K group. Spatial probe frequency in K,P,K+P decreased significantly compared to NS group(P<0.05) and spatial probe frequency in P,K+P increased significantly compared to K group (P<0.05).Conclusion:1.The neuron apotosis of infant rat could be induced by lasting anesthesia with Ketamine for 6 h, which might be one of the reasons of the infant rat long-term cognitive dysfunction.2.The neuron apoptosis and the long-term cognitive dysfunction could be attenuated by compound anesthesia of Ketamine and Propofol. The Bcl-2 upregulation induced by Propofol might play an important role in the protective mechanism.
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