| Objects: This study is designed to observe the improvement of exogenous IGF- 1 on spatial learning and memory ability of complete cerebral ischemia rats and the effects on the expression of p-Akt、p-m TOR. To reveal the possible mechanism of how IGF- 1 to improve cognitive impairment.Method: Adult male Wistar rats were randomly divided into five groups :normal control group, sham-operated group, dementia model group,IGF-1 group,IGF-1+PPP group. All groups except the normal control group were embedded micro-injection catheter into the lateral ventricle,After six days, the whole brain ischemia model was constructed except normal control group and sham-operated group by the classics Pulsinelli four vessels complete cerebral ischemia. Rats in the dementia model group received intraperitoneal injection 1ml DSMO(PPP solvent),intracerebroventricular injection NS 10 ul. Rats in the IGF-1 group received intraperitoneal injection 1ml DSMO(PPP solvent),intracerebroventricular injection IGF-1 10ul(0.2ug/ul) Rats in the IGF-1+PPP group received intraperitoneal injection 1ml PPP(20mg/kg, dissolved in 1ml DMSO),intracerebroventricular injection IGF-1 10ul(0.2ug/ul).Rats in the sham-operated group received intraperitoneal injection 1ml DSMO(PPP solvent),intracerebroventricular injection NS 10 ul. Intracerebroventricular injection of all groups was 30 minutes later than intraperitoneal injection.Continuous injecton 7 days and once a day.Morris water maze testing was respectively made before grouping and after the drug intervention. Water maze experiment including navigation test and space exploration. HE staining to observe neurons damage in the hippocampus CA1 area.Immunohistochemical method to detect the expression of p-Akt and p-m TOR protein in the rat hippocampal CA1 region of each group. Using the Image Pro Plus 6.0 software to process immunohistochemical images and calculate the IOD values. Results are processed using SPSS17.0 statistical software.Results:1)Morris water maze testing results: After the seven days drug intervention, the full-time average escape latency of the model group is longer than the normal control group and the sham-operated group(p<0.05), the full-time average escape latency of the IGF-1 group is shorter than the model group(p<0.05), the full-time average escape latency of the IGF-1+PPP group is longer than the IGF-1 group(p<0.05); The spanning platform times of the model group is less than the normal control group and the sham-operated group(p<0.05),the spanning platform times of the IGF-1 group is more than the dementia model group(p<0.05), the spanning platform times of the IGF-1+PPP group is less than IGF-1group(p<0.05); The original platform quadrant swimming time of the model group is shorter than the normal control group and the sham-operated group(p<0.05),the original platform quadrant swimming time of the IGF-1 group is longer than the model group(p<0.05), the original platform quadrant swimming time of the IGF-1+PPP group is shorter than the IGF-1 group(p<0.05).2) HE staining results: the cells were disorder and sparse in hippocampal CA1 regions of the model group compared with the normal group and the control group. At the same time, we can see irregular nucleus in the model group. Compared with the model group, the cells were neat and the structure was clear in hippocampal CA1 regions of the IGF-1 group. In wich the irregular cells decreased. The cells were disorder and sparse in hippocampal CA1 regions of the IGF1+PPP group. We also can see irregular nucleus contracting.3)Immunohistochemical staining results:Positive expression of p-Akt and p-m TOR protein can be seen in each group. However, positive expression of p-Akt and p-m TOR protein in the model group is more than the normal control group and the sham-operated group(p<0.05), positive expression of p-Akt and p-m TOR protein in the IGF-1 group is more than the model group(p<0.05),positive expression of p-Akt and p-m TOR protein in the IGF-1+PPP group is less than the IGF-1 group(p<0.05);the differences of p-Akt and p-m TOR protein positive expression between the model group and the IGF-1+PPP group has no statistical significance.Conclusion:1)IGF-1 can improve the spatial learning and memory ability of the whole cerebral ischemia in rats. With IGF-1 receptor blockers PPP, rats spatial learning and memory ability can not be improved.2) IGF-1 can improve the p- Akt, p- m TOR protein positive expression level in the whole cerebral ischemia rats of hippocampal CA1 region. With IGF-1 receptor blockers PPP,positive expression of p-Akt and p-m TOR protein of the whole brain ischemia rat hippocampal CA1 region in the IGF-1+PPP group is less than the IGF-1 group.So that IGF- 1 is through this way to active PI3K/AKT signaling pathway, promote p- Akt and p- m TOR protein expression, and improve spatial learning and memory ability of cerebral ischemia rats. |
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