川芎嗪对阿尔采末病模型小鼠学习记忆能力的影响及其机制初探

目的观察川芎嗪(tetramethylpyrazine,TMP)对AD模型小鼠学习记忆能力的改善作用及其机制。方法采用D-gal与NaNO2联合腹腔注射和AlCl3灌胃两种造模方法建立AD模型小鼠,灌胃给予TMP(100mg.kg-1)观察疗效,检测各组小鼠的逃避潜伏期、脑组织AChE、SOD活性、MDA含量及大脑皮层Aβ、NF-κB表达的变化。结果TMP可使D-gal与NaNO2联合诱导的AD模型鼠与AlCl3诱导的AD模型鼠的逃避潜伏期缩短(P<0.05);②TMP可使D-gal与NaNO2联合诱导的AD模型鼠与AlCl3诱导的AD模型鼠脑组织中,AChE活性分别降低16%和19%;使SOD活性分别提高50%和39%;使MDA含量分别降低27%和34%;上述检测结果与对照组比较差异均有显著性(P<0.05);③TMP可明显降低两种AD模型鼠脑组织中Aβ、NF-κB的表达(P<0.05)。结论TMP可改善化学诱导的AD模型小鼠学习记忆能力障碍,可能与提高SOD活性、降低MDA含量、降低AChE活性、降低脑组织中Aβ、NF-κB的表达等有关。

The effects of tetramethylpyrazine on learning and memory abilities of mice with Alzheimer disease and its possible mechanism

Aim To discuss the effects and mechanisms of tetramethylpyrazine(TMP)on learning and memory abilities of Alzheimer disease(AD)mice.Methods The animal models of AD were induced by two methods:one was intraperitoneally injected D-galactose(D-gal)and sodium nitrite(NaNO2)for thirty days,and another one was intragastricly administered aluminium trichloride(AlCl3)for forty days.TMP was intragastricly administered the two AD mice for twenty days,respectively.The escape latency of the mice in water maze test was recorded;AChE and SOD activities and MDA levels in the brain were detected by chemical colorimetric method;The expressions of Aβ and NF-κB in the cerebral cortex were measured by immunohistochemistry method.Results ① TMP has markedly decreased escape latency in D-gal and NaNO2 induced AD mice and AlCl3 induced AD mice,respectively(P<0.05).② In the brain of D-gal and NaNO2 induced AD mice,TMP reduced AChE activity 16%,decreased MDA levels 27% and increased SOD activity 50%,respectively;In the brain of AlCl3 induced AD mice,TMP reduced AChE activity 19%,decreased MDA levels 34% and increased SOD activity 39%,respectively;these results showed significant difference compared with model mice group(P<0.05).③ TMP also decreased Aβ and NF-κB expressions in the cerebral cortex of two AD mice models(P<0.05).Conclusions In D-gal and NaNO2 induced AD mice and AlCl3 induced AD mice,TMP can remarkably enhance the learning and memory abilities,presumably in relation to raising the activity of SOD,reducing the activity of AChE,the levels of MDA and the expressions of Aβ and NF-κB in the brain.