香菇多糖联合依地酸钙钠对铅中毒小鼠学习记忆功能及胆碱能神经功能的影响

The Influence of Combined Application of Lentinan and Calcium Disodium Edetate on Learning,Memory Ability and the Function of the Central Cholinergic System in Lead Poisoning Mice

目的:研究香菇多糖联合依地酸钙钠对铅中毒小鼠学习记忆功能的影响,并初步探讨其作用机制。方法:将50只昆明种小鼠随机分为5组,即正常对照组、模型对照组、阳性对照依地酸钙钠组、香菇多糖低剂量联合依地酸钙钠组、香菇多糖高剂量联合依地酸钙钠组。正常对照组ip等量生理盐水,每日1次,其他组ip质量分数为2%的Pb(Ac)2溶液70 mg·kg-1,每日1次,连续给药8 d,复制铅中毒模型。然后正常对照组、模型对照组ip等量生理盐水,共7 d,其他组ip依地酸钙钠80 mg·kg-1,共3 d。同时香菇多糖低剂量联合依地酸钙钠组、香菇多糖高剂量联合依地酸钙钠组分别ip依地酸钙钠和香菇多糖1.5,3.0 mg·kg-1,共7 d。采用小鼠跳台法、Morris水迷宫法检测小鼠学习记忆功能,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,HE染色观察海马组织形态学改变。结果:香菇多糖高剂量联合依地酸钙钠组能显著改善铅中毒所致的学习记忆障碍。与模型对照组相比,香菇多糖高剂量联合依地酸钙钠组逃离潜伏期明显缩短(P<0.01),停留潜伏期明显延长(P<0.01),错误数减少(P<0.01),TChE活力显著降低(P<0.01),ChAT活力显著增高(P<0.01),并显著改善了海马神经元的变性、脱落。与依地酸钙钠80 mg·kg-1组相比,香菇多糖高剂量联合依地酸钙钠组逃离潜伏期明显缩短(P<0.05),停留潜伏期明显延长(P<0.01),错误数减少(P<0.01),TChE活力显著降低(P<0.01),ChAT活力显著增高(P<0.01),且优于香菇多糖低剂量联合依地酸钙钠组。结论:香菇多糖联合依地酸钙钠能改善铅中毒小鼠的学习记忆功能,其作用机制可能与降低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 study the effect of learning and memory ability on lead poisoning mice treated by lentinan and calcium disodium edetate, and to explore the mechanism preliminarily. Method： Fifty mice were randomly divided into five groups, control group, model group, positive control group, lentinan low dose group and high dose group. The mice in the control group were given intraperitoneal injection of saline at the same dosage, and the mice in other groups were given intraperitoneal injection of 2%Pb（Ac）2 solution （70 mg· kg^ -1） for 8 days. Then the mice in the control group and model group were given intraperitoneal injection of saline at the same dosage for seven days, and the mice in other groups were given intraperitoneal injection of calcium disodium edetate （80 mg· kg^ -1 ） for three days, at the same time the mice in lentinan low dose group and high dose group were given intraperitoneal injection of lentinan （1.5 mg· kg^ -1 and 3.0 mg· kg-1） for Seven days. Step-down test and Morris water maze were used to monitor the learning and memory ability. In the mean time, the activity of choline acetyhransferase （CHAT） and ture choline esterase （TChE） was measured by biochemical methods. And the alterations in hippocampus slices morphology were assessed using microscope. Result： The learning and memory ability of lead poisoning mice could be markedly improved by lentinan high dose group. Compared with model group, the escape latency of mice in lentinan high dose group was markedly shortened （P 〈 0.01 ） , and the retention latency of mice was markedly lengthened （P 〈 0. 01 ）, and the fault numbers were markedly reduced （P 〈 0.01 ）. The activity of ChAT was markedly decreased （P 〈 0.01 ） and TChE was markedly increased （P 〈 0.01 ）. The degenerative changes of neuron in hippocampus slices were improved. Compared with positive control group, the escape latency of mice in lentinan high dose group was shortened （P 〈 0.05 ） , and the retention latency of mice was markedly lengthened （P 〈 0.01 ） , and the fault numbers were markedly reduced （P 〈 0.01 ）. The activity of ChAT was markedly decreased （P 〈 0.01 ） and TChE was markedly increased （P 〈 0.01 ）. Conclusion： The combined application of lentinan and calcium disodium edetate could improve the learning and memory ability in lead poisoning mice. The mechanism may be related to increasing the activity of ChAT and decreasing the activity of TChE and the improvement of the function of the central cholinergic system.