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目的观察左旋丁苯酞(L-NBP)对慢性脑缺血大鼠认知的改善作用以及对海马β-淀粉样肽(Aβ1-42)水平以及Tau蛋白磷酸化的影响,探讨其作用机制。方法采用结扎双侧颈总动脉建立慢性脑缺血模型,实验分四组:假手术组、模型组、L-NBP 30 mg/kg组和L-NBP 120 mg/kg组。假手术组、模型组予植物油灌胃治疗,L-NBP30 mg/kg组和L-NBP 120 mg/kg组连续给予45 d治疗,用Morris水迷宫检测大鼠的空间学习和记忆能力。采用酶联免疫吸附试验法检测大鼠海马组织中Aβ1-42的含量;采用免疫印迹法检测Tau蛋白的磷酸化水平,HE染色检测海马神经元的形态。结果在水迷宫空间探索实验中,L-NBP 30 mg/kg组和L-NBP 120 mg/kg组大鼠在目标象限时间百分比分别为(26.3±6.4)%和(28.6±5.8)%,与模型组[(15.2±5.2)%]比较,差异均有高度统计学意义(P<0.01);L-NBP明显减少了大鼠海马Aβ1-42含量,L-NBP 30 mg/kg组和L-NBP 120 mg/kg组分别为(1.07±0.30)和(0.99±0.18),L-NBP 120 mg/kg组与模型组(1.36±0.24)比较差异有高度统计学意义(P<0.01);L-NBP 30 mg/kg组及L-NBP 120 mg/kg组大鼠海马组织磷酸化Tau蛋白表达水平[(1.72±0.18)、(1.43±0.35)]较模型组(1.82±0.23)明显降低,L-NBP120 mg/kg组与模型组比较,差异有统计学意义(P<0.05)。HE染色观察到L-NBP可明显改善海马神经元的形态异常。结论 L-NBP改善慢性脑缺血大鼠的学习记忆缺陷,是通过减少海马Aβ1-42的水平,减轻Tau蛋白的磷酸化,改善海马神经元的形态异常,保护了海马神经元。
Objective To observe the effect of L-NBP on cognitive function in chronic cerebralischemia rats and its effect on the level of β-amyloid peptide (Aβ1-42) and phosphorylation of Tau in hippocampus and to explore its mechanism. Methods Chronic cerebral ischemia model was established by ligation of bilateral common carotid arteries in four groups: sham-operation group, model group, L-NBP 30 mg / kg group and L-NBP 120 mg / kg group. The rats in the sham operation group and the model group were given gavage with vegetable oil. The rats in the L-NBP30 mg / kg and L-NBP 120 mg / kg groups were given 45 days of continuous treatment. Morris water maze test was used to detect the spatial learning and memory ability. The content of Aβ1-42 in rat hippocampus was detected by enzyme-linked immunosorbent assay (ELISA). The phosphorylation of Tau protein was detected by Western blotting. The morphology of hippocampal neurons was detected by HE staining. Results In the water maze space exploration experiment, the percentages of time in the target quadrant were (26.3 ± 6.4)% and (28.6 ± 5.8)% in the L-NBP 30 mg / kg and L-NBP 120 mg / L-NBP significantly reduced the content of Aβ1-42 in hippocampus of rats in model group [(15.2 ± 5.2)%], the difference was statistically significant (P <0.01) (1.07 ± 0.30) and (0.99 ± 0.18) respectively in NBP 120 mg / kg group and 1.36 ± 0.24 in L-NBP 120 mg / kg group (P <0.01); L Compared with model group (1.82 ± 0.23), phosphorylated Tau protein expression in hippocampus of rats in NBP 30 mg / kg group and L-NBP 120 mg / kg group [(1.72 ± 0.18), (1.43 ± 0.35) L-NBP120 mg / kg group compared with the model group, the difference was statistically significant (P <0.05). HE staining observed L-NBP can significantly improve the morphological abnormalities of hippocampal neurons. Conclusion L-NBP improves learning and memory deficits in rats with chronic cerebral ischemia by decreasing the level of Aβ1-42 in the hippocampus, alleviating the phosphorylation of Tau protein, improving the morphological abnormality of hippocampal neurons and protecting the hippocampal neurons.