| Objective: To observe the dynamic changes of serum growth factor and growth hormone(growth hormone,GH)in chronic cerebral ischemia rats and the effects of rhGH on serum growth factor and learning,memory in vascular dementia model rats induced by chronic cerebral ischemia rats.To explore the brain protection action mechanism of recombinant human growth hormone.Method: 1,Morris water maze was used to selecte 143 male SD rats with normal learning and memory ability,these rats distribute to the experimental groups randomly,then established VD rats model induced by chronic cerebral ischemia.After surgery,the subcutaneous neck injection way to give rhGH of treatment groups and observed the learning and memory ability by water maze experiment when finish the injection after 28 days;2,After cerebral ischemia,selecteing 8 rats in each group at the corresponding point of time,ELISA was used to assay the levels of vascular endothelial growth factor(VEGF),insulin-like growth factor-1(IGF-1)and growth hormone(GH)in serum,cortex and hippocampus homogenate.Another part of rats isolate brains,the brains can be fixed in paraffin section for HE staining and TUNEL apoptosis staining to observe the neuron changes and neuronapoptosis.TUNEL images processing can be used by Image Pro Plus software and then figure out the IOD values.Results:1.With the time of chronic cerebral ischemia,compared with normal control group,the VEGF,IGF-1 and GH levels in serum,cortex and hippocampus of model groups are decreased with significant difference(p<0.05)and the VEGF and IGF-1 in serum,cortex and hippocampus were positive correlated to GH level;The brain tissue of model group in HE staining was observed under light microscope,We found that the number of normal neurous reducing and disordered,cell with irregular shape,nucleus pycnosis,dissolved in hippocampal CA1 region with cerebral ischemia,but there was no change in normal group.2.Water maze experiment,all rats shortened their escape latency following with the increasing of training time.On the place navigation test day of six,the escape latency in normal control group,model group(28d)and rhGH group(28d)were 5.29±3.41 s,23.45±3.58 s and 7.30±5.39 s,the frequency of space probe test were5.87±3.27,1.32±1.19 and 3.14±1.50.We can found that compared with normal group,the model group(28d)learning and memory ability was notablely decreased,and the difference is significant(p < 0.05).rhGH group(28d)and model group(28d)spatial memory ability comparison,there was significant difference(p < 0.05),there was no significant difference between the normal group and the model groups.Compared with model groups,rhGH groups serum,cortex and hippocampus VEGF,IGF-1 and GH levels were significantly increased(p<0.05);the VEGF and IGF-1 in serum,cortex and hippocampus were linear correlation with GH;rhGH groups compared with model groups,positive staining of apoptosis neuron was reduced and distribution density was increased in CA1 region of hippocampal.rhGH groups IOD values reduction compared with model groups,there were significant differences(p <0.05).Conclusion:With the time of chronic cerebral ischemia,the IGF-1,VEGF level in serum,cortex and hippocampus were lower which were found in the chronic cerebral ischemia model and IGF-1,VEGF level have the linear correlation with GH in serum,cortex and hippocampus.rhGH can increase the level of GH and IGF-1,VEGF on the serum,cortex and hippocampus in vascular dementia model rats,improve the learning,memory and cognitive impairment caused by chronic cerebral ischemia.rhGH can relieve the apoptosis of neuron in hippocampus and these results suggest that rhGH plays an important role in protecting chronic cerebral ischemic damage in VD rats. |
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