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目的研究川芎嗪注射液对铅中毒小鼠学习记忆功能的影响。方法将50只健康4周龄清洁级昆明小鼠按体重随机分为5组,分别为空白对照(生理盐水)组、铅中毒组、阳性对照组和低剂量川芎嗪治疗组、高剂量川芎嗪治疗组,每组10只。除空白组外,其他4组腹腔注射70 mg/kg乙酸铅溶液,染毒容量为14 ml/kg,每日1次,连续注射8 d。铅中毒模型复制完成后恢复3 d,空白组和铅中毒组均连续7 d腹腔注射生理盐水;低、高剂量川芎嗪治疗组分别连续7 d腹腔注射40、80 mg/kg川芎嗪溶液;阳性对照组前3 d腹腔注射80 mg/kg依地酸钙钠溶液,后4 d腹腔注射等量生理盐水;注射容量为20 ml/kg,每日1次。采用Morris水迷宫法检测小鼠学习记忆能力,采用生物化学法检测小鼠大脑组织中乙酰胆碱转移酶(ChAT)及乙酰胆碱酯酶(TChE)的活力,并计算海马细胞坏死率。结果与空白组相比,铅中毒组小鼠逃避潜伏期明显延长,海马细胞坏死率和脑组织中TchE活力明显升高,脑组织中ChAT活力显著降低,差异有统计学意义(P<0.05)。与铅中毒组相比,高剂量川芎嗪治疗组小鼠逃避潜伏期明显缩短,海马细胞坏死率明显下降,脑组织中ChAT活力显著提高,而各剂量川芎嗪治疗组小鼠脑组织中TchE活力明显降低,差异有统计学意义(P<0.05)。且随着川芎嗪溶液染毒剂量的升高,铅中毒小鼠海马细胞坏死率和脑组织中TchE活力呈下降趋势,脑组织中ChAT活力呈上升趋势,逃避潜伏期呈缩短趋势。结论川芎嗪注射液能改善铅中毒小鼠的学习记忆能力,其作用机制可能与其降低小鼠脑组织中TchE活力、提高ChAT活力,增强中枢胆碱能神经系统功能有关。
Objective To investigate the effects of ligustrazine injection on learning and memory in lead poisoning mice. Methods Fifty healthy 4-week-old clean Kunming mice were randomly divided into 5 groups according to body weight. They were blank control (saline) group, lead poisoning group, positive control group and low dose ligustrazine treatment group, high dose ligustrazine Treatment group, 10 in each group. Except for the blank group, the other four groups were injected intraperitoneally with 70 mg / kg lead acetate solution at a dose of 14 ml / kg once daily for 8 days. The model of lead poisoning was resumed 3 days after the replication was completed. The rats in the blank group and the lead poisoning group were given intraperitoneal injection of saline for 7 consecutive days. The rats in the low and high doses of ligustrazine group were injected intraperitoneally with 40 and 80 mg / kg of ligustrazine solution for 7 days respectively. The control group was intraperitoneally injected with 80 mg / kg calcium sodium edetate solution 3 d before, and the same volume of saline was injected intraperitoneally 4 d after injection. The injection volume was 20 ml / kg once daily. The learning and memory abilities of mice were detected by Morris water maze test. The activity of acetylcholinesterase (ChAT) and acetylcholinesterase (TChE) in brain tissue of mice were detected by biochemistry method, and the hippocampal cell necrosis rate was calculated. Results Compared with the blank control group, the escape latency of the mice in lead poisoning group was significantly prolonged. The necrosis rate of hippocampus and TchE activity in brain tissue were significantly increased. The activity of ChAT in brain tissue was significantly decreased (P <0.05). Compared with lead poisoning group, high dose Ligustrazine treatment group mice evidently shortened escape latency, hippocampal cell necrosis decreased significantly, brain activity of ChAT increased significantly, and the dose of ligustrazine treatment group mice brain TchE activity was significantly Reduce, the difference was statistically significant (P <0.05). And with the increase of dose of Ligustrazine injection, the hippocampal cell necrosis rate and TchE activity in brain tissue of lead poisoned mice decreased. The activity of ChAT in brain tissue showed an upward trend and the escape latency shortened. Conclusion Ligustrazine injection can improve the learning and memory abilities of lead poisoning mice. Its mechanism may be related to the decrease of TchE activity, the increase of ChAT activity and the central cholinergic system function in mice.