摘要:
目的：探讨阿尔茨海默病(AD)与铝中毒的关系及土茯苓治疗的效果的观察。方法：将53只小鼠分为正常组、模型组、治疗1组和治疗2组，除正常组外，造模组用D-半乳糖 + AlCl3混合水溶液腹腔注射60天，建立拟老年痴呆症(阿尔茨海默病)模型。治疗1、2组在铝染毒1个月后同时分别给予中药复方制剂不同剂量灌胃，模型组和正常组用等量体积蒸馏水灌胃，直至实验结束。在实验前、中、后分别进行水迷宫游水试验，并测定血红蛋白；实验结束后取血，分离血清，测定血清生化指标；处死小鼠取脑，制成10%脑匀浆，分别测定脑中乙酰胆碱酯酶(AchE)、乙酰胆碱转移酶(chAT)活力、超氧阴离子自由基清除率、谷胱甘肽等相关生化指标含量；另一部分脑用甲醛处理后作病理检查。结果：正常组、模型组、治1组、治2组依次为，脑铝Al3+含量2.17 ± 0.06、2.41 ± 0.07、1.40 ± 0.49、1.14 ± 0.02 (µmol/L)，各组间比较，p < 0.01，差异有统计学意义；血清Al3+含量，1.81 ± 0.13、2.89 ± 0.26、2.62 ± 0.08、2.41 ± 0.30 (µmol/L)，各组间比较，p < 0.01，差异有统计学意义，正常组小鼠血清铝Al3+含量明显低于其他3组，模型组，治1组明显高于其他二组；脑乙酰胆碱酯酶(AchE)活力：2.22 ± 0.74、1.18 ± 0.35、1.64 ± 0.40、1.76 ± 0.42 (U/mg∙prot)，p < 0.05，差异有统计学意义；模型组明显降低；脑乙酰胆碱转移酶(chAT)活力依次为，59.67 ± 9.73、32.84 ± 13.12、28.23 ± 5.63、25.07 ± 4.89 (U/g组织湿重)，正常组明显差高于其他各组，p < 0.01，差异有统计学意义；造模前、中、后Hb含量，组间比较，实验前：各组无显著性差异；造模后和治疗后，与正常组比较，p < 0.01，差异有统计学意义；超氧阴离子自由基( )组间比较，p < 0.01，差异有统计学意义；谷胱甘肽，组间比较，与正常组比较，治疗1组p < 0.05，与模型组比较，治疗2组p < 0.05，治疗1组p < 0.01，差异有统计学意义；血清甘油三酯(TG)、总胆固醇(TC)、尿素氮各组间比较，p < 0.05，差异有统计学意义；血清谷丙转氨酶(ALP)、脑丙二醛(MDA)浓度(nmol/mg, prot)治疗1组、治疗2组明显低于正常组、模型组；在水迷宫试验中，造模前、造模后(治疗前)水迷宫时间，各组间无明显差异，但模型组、治1组己有延长趋势，治疗后各组间已有明显差异，且前、中、后的水迷宫错误率和失败率都有明显的差异。结论：高铝抑制了(chAT)活性，使乙酰胆碱(Ach)合成减少，导致AchE活性下降，抗氧化能力降低及记忆功能障碍；且本中药复方制剂通过排铝、提高抗氧化能力治疗后对老年认知功能障碍有明显疗效。
Abstract:
Objective: To evaluate the association between aluminum poisoning and Alzheimer’s disease (AD) and observe the therapeutic effect of Smilax glabra. Methods: 53 mice were divided into four groups: control group, model group, treated group 1, treated group 2. Except control group, the rest of groups were made Alzheimer's disease models by IP injection with D-galactose and AlCl3 mixed solution for 60 days. Mice of treated group 1 and treated group 2 were given different doses of traditional Chinese medicine, containing Poria Chinensis, in different doses by gavage after 1 month of aluminum poisoning. The modeled group and the control group were gavaged with the same volume of distilled water until the end of the experiment. The water maze swimming test was made respectively before, during and after the experiment, and the hemoglobin was measured. After the experiment, the blood was taken, the serum was separated, and the serum biochemical indexes were measured. The mice were killed, and the brain homogenate was made. The contents of AchE, scavenging rate of superoxide anion radicals, glutathione and other related biochemical indexes in the brain were determined. The other part of the brain was treated with formaldehyde for pathological examination. Results: The Al3+ content of the brain was 2.17 ± 0.06, 2.41 ± 0.07, 1.40 ± 0.49, 1.14 ± 0.02 (µmol/L) in the control group, the model group, the treated group 1, and the treated group 2 respectively (p < 0.01); and the Al3+ content of the serum was 1.81 ± 0.13, 2.89 ± 0.26, 2.62 ± 0.08, 2.41 ± 0.30 (µmol/L) (p < 0.01) respectively. The difference was statistically significant. The serum Al3+ content of the control group was significantly lower than that of other 3 groups, and that of the model group and the treated group 1 were significantly higher than other 2 groups. The activities of AchE among the control group, the model group, the treated group 1 and the treated group 2 were 2.22 ± 0.74, 1.18 ± 0.35, 1.64 ± 0.40, and 1.76 ± 0.42 (U/mg∙prot); the activity in the modeled group was significantly reduced, with statistical significance, p < 0.05. The activities of chAT were: 59.67 ± 9.73, 32.84 ± 13.12, 28.23 ± 5.63, and 25.07 ± 4.89 (U/g tissue wet weight); the activity in the control group was significantly higher than other groups, p < 0.01. The content of hemoglobin, before, during and after modeling, compared before the experiment, showed no significant difference between groups. After the modeling and the treatment, the modeled group and the two treated groups were significantly different from the normal group, p < 0.01. The comparison between the groups of superoxide anion radicals was statistically significant, p < 0.01. These differences were statistically significant, compared between groups of glutathione, compared with the normal group, treatment group 1 p < 0.05; compared with the model group, p < 0.05 in the treatment group 2 and p < 0.01 in the treatment group 1. Comparing serum triglyceride (TG), total cholesterol (TC), and urea nitrogen between groups, p < 0.05, the difference was statistically significant. In the water maze test, there was no significant difference in the latency time to find the platform before and after the modeling (before the treatment), but the modeled group and the treatment group 1 had a prolonged trend. Nonetheless, there were some differences between each group after the treatments. In addition, there were significant differences in the error rate and failure rate between all groups, before experiment, after modeling, and after treatments. Conclusion: Aluminum can induce atrophy, degeneration and apoptosis of neurons in the brain, resulting in a decrease in AchE activity and a decrease in antioxidative capacity. The extract prepared from traditional Chinese medicine ameliorated the effects on chAT, Ach, AchE, and oxidative capacity in the Alzheimer’s model induced by Al poisoning.