川芎嗪对三氯化铝致阿尔茨海默病模型小鼠学习记忆能力的影响

Effects of tetramethylpyrazine on learning and memory in aluminium trichloride induced Alzheimer＇ s disease mice

目的观察川芎嗪（TMP）对阿尔茨海默病（AD）模型小鼠学习记忆能力的改善作用及其机制。方法采用AlCl3灌胃方法建立AD模型小鼠，灌胃给予TMP（200mg·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1）TMP可使AlCl3、诱导的AD模型鼠的逃避潜伏期显著缩短（P〈0．05）；2）TMP可使AlCl3诱导的AD模型鼠脑组织中AChE活性降低19％[（1．37±0．13）U·mgpro^-1，（1．69±0．27）U-mgpro^-1，P=0．016]；使SOD活性提高39％[（55．81±10．25）U·mgprot^-1，（40．04±13．06）U·mgprot^-1，P=0．026]；使MDA含量降低34％[（43．63±13．27）nmol·mgprot^-1，（28．59±8．52）nmol·mgprot^-1，P=0．023]；3）TMP可明显降低AD模型鼠脑组织中Aβ、NF—KB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，可能机制与提高SOD活陛、降低MDA含量、降低AChE活性、降低脑组织中Aβ、NF—κB的表达等相关。

Objective To discuss the effects and mechanisms of tetramethylpyrazine （TMP） on learning and memory abilities of Alzheimer＇ s disease （AD） mice. Methods The animal models of AD were induced by aluminium trichloride （AlCl3） intragastriely for forty days. Then,TMP was intragastricly administered for twenty days. The escape latency of the mice in water maze test was recorded ; and AChE and SOD activities and MDA levels in the brain were detected by chemieal colorimetric method. The expressions of Aβ and NF-κB in the cerebral cortex were measured by innnunohistochemistry method. Results 1 ） TMP has markedly decreased escape latency in AlCl3 induced AD mice（P 〈 0.05）. 2） In the brain of AlCl3 induced AD mice,TMP reduced AChE activity 19%[（1.37±0. 13） U·mgpro^-1 vs （ 1.69 ±0.27） U · mgprot^-1, P=0.016 ],decreased MDA levels 34% [ （43.63 ±27） nmol. mgprot ^-1 vs （28.59 ±8.52 ） nmol · mgprot^-1 , P= 0. 0231 and increased SOD activity 39%[（55.81 ± 10.25 ） U · mgprot^-1 vs （40.04±13.06）U · mgprot^-1,P=0.0261,respectively.These resuits showed significant difference with model mice group （P〈 0.05 ）. 3） TMP also decreased Aβ and NF-κB expressions in the eerebral cortex of AD mice models （P〈 0.05）. Conclusion In AlCl3 induced AD mice,TMP can remarkably enhance the learning and memory abilities, presumably in relation to raise the aetivity of SOD, reduce the activity of AChE,the levels of MDA and the expressions of Aβ and NF-κB in the brain.