通过观察大鼠全脑缺血再灌注后不同时限经侧室注入（INS）对海马CAI区神经元的形态学及大鼠记忆力改变的影响，获取INS对缺血性脑损伤产生中枢直接保护作用的证据及最咽褂檬奔洹Ｒ苑肿由镅Х椒ㄎ侄危芯縄NS与缺血相关神经活性物质及细胞凋亡的关系。探明INS产生中枢直接保护作用的机理。为INS治疗缺血性性脑损伤提供理论依据。

To get the evidance of the neuroprotevtive effect of insulin on brain ischemia and the best time of administration, and to explore the mechanism of neuroprotective of insulin on brain ischemic injury. Method: The global brain ischemic model of rat was established. The light microscope, the electron microscope, the in situ DNA end labeling (ISEL), the immunohistochemical analyse, the RT-PCR, and the HPLC-ED were used to observed the apoptosis of neuron, the express of apoptosis correlation protein and the changes of monoamine neurotransmitters in hippocampal CA1 region of rat post global brain ischemia with intraventricle administrtation of insulin.Result: Insulin, injected within 6 hours after ischemia, has an neuroprotective effect on neurons in hippocampal CA1 region. The best time of administration of insulin was at the time of immdiatelly post re-perfusion, and the best dose is 1.0U; The neuroprotective effect of insulin on rat post global brain ischemia can not only attenuate the delayed neuron death in CA1 region, but also improve the ability of memory deficit.; Intraventricle injection of insulin, following global brain ischemia, can up-regulate the translation of the Bcl-2 and Bcl-xl gene to improve the expression of the Bcl-2 and Bcl-xl protein in CA1 region,; Intraventricle injection of insulin, post global brain ischemia, can change the levels of monoamine neurotransmitters and correct the metabolic disorder by affecting the release and reuptake of monoamine neurotransmitters, adjusting the contents and activities of synthetases and catabolic enzymes. Conclusion: This study demonstrate that insulin has the neuroprotective effect on brain ischemic injury and the mechanism of its protective effect consists in two ways. One is that insulin can improve the expression of the Bcl-2 and Bcl-xl protein in CA1 region by up-regulating the translation of the Bcl-2 and Bcl-xl gene to reduce the apoptosis of neurons in CA1 region post brain ischemia. Another is that insulin can change the levels of monoamine neurotransmitters and correct the metabolic disorder by affecting the release and reuptake of monoamine neurotransmitters, adjusting the contents and activities of synthetases and catabolic enzymes to attenuate the brain ischemic insult.