Objective To observe the effects of recombinant human growth hormone (rhGH) on the ability of learning,memory and space exploration of rats with vascular dementia (VD) and to explore its possible mechanism.Methods Forty-five rats were randomly divided into three groups:the experimental group,model group,and normal group,with 15 rats in each.The VD model was prepared in the experimental group and the model group through bilateral carotid artery ligation at different time points (we ligated the right carotid artery three days after the left carotid artery was ligated).The normal group used the same method to separate the bilateral carotid arteries,but we did not ligate the common carotid artery.At the beginning of the first day after modeling,rhGH (0.2 IU/100 g) was injected into the neck of the rats in the experimental group,while rats of the normal group and model group were given the same amount of normal sodium once a day for 28 days.Water maze test was used to assess the ability of learning and memory and space exploration of rats.ELISA was used to detect the levels of vascular endothelial growth factor (VEGF),insulin-like growth factor 1 (IGF-1) and growth hormone (GH) in the serum,cortex,and hippocampus.TUNEL apoptosis staining was used to observe the status of neuronal apoptosis (IOD value).Results Compared with the normal group,the experimental group from the first to the fourth day and the model group from the first to the sixth day had longer escape latency (P ＜ 0.05).Compared with the model group,the experimental group had shorter escape latency on the 2nd,4th,5th,and 6th days (P ＜0.05).Compared with the model group,the experimental group and the normal group passed the platforms more (P ＜ 0.05).Compared with model group,the levels of VEGF,IGF-1,and GH in the serum,cortex,and hippocampus of the experimental group increased (all P ＜ 0.05).Compared with the normal group,the levels of VEGF,IGF-1,and GH in the serum,cortex,and hippocampus of the model group decreased (all P ＜ 0.05).Compared with the model group,the IOD value of TUNEL apoptosis staining in the hippocampus of the experimental group and the normal group decreased (P ＜ 0.05).Conclusion The rhGH can improve the ability of learning,memory,and space exploration in VD rats by increasing the VEGF and IGF-1 levels in the serum,cortex,and hippocampus.%目的 观察重组人生长激素(rhGH)对血管性痴呆(VD)大鼠学习记忆能力、空间探索能力的影响,并探讨其可能机制.方法 45只大鼠随机分为实验组、模型组、正常组各15只,其中实验组和模型组通过不同时间点双侧颈总动脉结扎法(结扎左侧颈总动脉3d后再结扎右侧颈总动脉)制备VD模型,正常组用同样方法分离双侧颈总动脉,但不结扎颈总动脉;造模后第1天开始,实验组大鼠颈部皮下注射rhGH(0.2 IU/100 g),正常组和模型组给予等量生理盐水,1次/d,连续28 d.采用水迷宫实验评价大鼠学习记忆能力及空间探索能力,ELISA法检测血清、皮质、海马中血管内皮生长因子(VEGF)、胰岛素样生长因子1(IGF-1)、生长激素(GH),TUNEL凋亡染色观察神经元凋亡情况[以积分光密度值(IOD值)表示].结果 与正常组比较,实验组第1～4天及模型组第1～6天逃避潜伏期长(P均＜0.05);与模型组比较,实验组第2、4、5、6天逃避潜伏期短(P均＜0.05).与模型组比较,实验组、正常组经过平台次数多(P均＜0.05).与模型组比较,实验组血清、皮质、海马中VEGF、IGF-1、GH水平升高(P均＜0.05);与正常组比较,模型组血清、皮质、海马中VEGF、IGF-1、GH水平降低(P均＜0.05).与模型组比较,实验组、正常组海马TUNEL凋亡染色IOD值降低(P均＜0.05).结论 rhGH可改善VD大鼠学习记忆能力、空间探索能力,其机制可能与其可增加血清、皮质、海马中VEGF和IGF-1水平有关.
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