瘦素对血管性痴呆大鼠认知功能的改善作用

目的 研究瘦素脑内注射对双侧颈总动脉永久性结扎(2VO)所致血管性痴呆(VaD)大鼠认知功能的改善作用.方法 在缺糖缺氧培养条件下,观察瘦素对体外培养的海马神经元的保护作用,以及Western Blotting检测海马神经元瘦素受体的表达.在大鼠海马区预注射瘦素的基础上,用2VO法制作VaD大鼠模型,Morris水迷宫测试瘦素治疗后认知功能的改善情况,Tunel染色测定各组大鼠海马脑组织内细胞凋亡的变化.结果 体外培养海马神经元上存在着瘦素受体的表达,在缺糖缺氧培养12h后,海马神经元出现大量的细胞凋亡,凋亡率为(72.96±6.25)%,而在瘦素预处理1μg和5μg组,细胞凋亡率分别为(46.33 ±7.85)%和(23.58±5.08)%,与对照组相比,差异有统计学意义(P<0.01).瘦素脑内注射的VaD大鼠,与未予治疗的VaD大鼠组相比,VaD瘦素治疗组大鼠找到平台的潜伏期缩短(P<0.01),找到平台的平均速度加快(P<0.01),与痴呆组相比,瘦素治疗组大鼠脑组织海马区凋亡细胞数明显减少,差异具有统计学意义(P<0.01).结论 瘦索对大鼠体外培养和脑组织内海马神经元具有神经保护作用,脑内注射瘦素可以明显改善VaD大鼠的认知功能.

Cognitive function improvement after administration of leptin into brain of rats with vascular dementia

Objective To study improvement of cognitive function impairment of vascular dementia rats induced by a permanent bilateral ligation of common carotid arteries (2VO) after administration of leptin in brain. Methods Hippocampal neurons was isolated and cultured from SD rats. At oxygen-glucose deprivation condition, protection role of leptin on hippocampal neurons was observed and expression of leptin receptor was detected. Animal model of rats was established by 2VO. Pre-treatment VaD model of leptin was established by administration leptin into hippocampus region. The Morris water test was performed to detect difference in the cognitive function between VaD group and control group. Neuron apoptosis in hippocampus tissue were determined with TUNEL. Results Leptin receptor expression could be seen in hippocampal neurons. After oxygen-glucose deprivation cultured for 12 h , plenty of apoptotic cells were seen in hippocampal neurons, apoptosis rat was up to (72.96 ± 6.25) % , while apoptosis rate was (46.33 ±7.85)% and (23.58 ±5.08)% in 1 ( μg and 5μg leptin treatment group,respectively. Compared leptin treatment group with control group,difference had a statistical significance(P<0.01). Compared with untreated VaD group, latency time was shorter and average velocity was increased in leptin-treat-ment VaD group. Neuron apoptosis in hippocampus tissue of leptin-treated group were different significantly from those of untreated group (P < 0.01). Conclusion Leptin could protect hippocampal neurons from apoptosis in vitro. Cognitive function impairment could be improved by administration of leptin into brain in VaD rats.