Nec-1对铝致小鼠认知能力影响的拮抗作用

Antagonistic Effect of Nec-1 on Cognitive Ability in Aluminum-induced Mice

目的研究Necrostatin-1(Nec-1)对铝致小鼠空间学习和记忆影响的拮抗作用及代谢型谷氨酸受体-1(mGluR1)的表达。方法经Morris水迷宫实验筛选昆明小鼠按体重随机分为4组,即0 mmol Nec-1对照组、2 mmol Nec-1组、4 mmol Nec-1组和8 mmol Nec-1组,每组10只。经侧脑室注射染毒AlCl3和Nec-1,AlCl33μl/d,Nec-1 2μl/d,连续5 d,染毒期结束后从第15天开始用Morris水迷宫实验判断给药后各剂量组小鼠的认知能力;染毒期结束20天后断头取脑组织,用Western-blot的方法检测mGluR1蛋白量;用荧光定量PCR方法检测mGluR1基因表达。结果 Morris水迷宫实验结果显示,随着Nec-1剂量的增加小鼠找到平台的潜伏期较对照组明显缩短(P<0.05),而空间探索实验中目标象限停滞时间明显延长(P<0.05);mGluR1蛋白量随着Nec-1剂量的增加而明显降低(P<0.01)。mGluR1基因总量随着Nec-1剂量的增加而降低,其中8 mmol Nec-1组较对照组明显降低(P<0.05)。结论 Nec-1对铝的神经毒性有抑制作用,减轻铝对小鼠认知能力的影响,且可使与认知能力相关蛋白和mGluR1的表达降低。

Objective To investigate the antagonistic effects of necrostatin-1 （nec-1）on space learning and memory and the expression of metabolic glutamate receptor-subtype 1 （mGluR1）in aluminum-induced mice. Methods After being trained by Morris water maze（MWM）, normal Kunming mice were screened and evenly and randomly divided into 4 groups with 10 in each, i. e. 0 mmol nec-1 as the control group, 2 mmol nec-1 group, 4 mmol nec-1 group and 8 mmol nec-1 group. Every group was exposed to nec-1（2 μl/d）and AlCl3 （3 μl/ d）hy lateral ventricle injection successively for 5 days. Cognitive ability was evaluated by MWM on the 15th day after nec-1 treatment for 5 days. Cerebral cortex was taken from mice on the 20th day after nec-1 treatment for 5 days. The expression of mGluR1 protein in cytoplasm was detectedquantitatively by Western- blot and mGluR1 gene was detected by fluorescence quantitative PCR. Results MWM experiments showed that the latency for mice to find the platform was shortened significantly than that of the control group as nec- 1 dosage increasing in space navigation test（P〈0.05）. The time in goal quadrant increased significantly than that of the control group in exploration space test （P 〈 0.05）. The expression of mGluR1 protein was significantly decreased than that of the control group as nec-1 dosage increasing（P〈0. 01）. The expression of mGluR1 genes decreased than that of the control group as nec-1 dosage increasing and it decreased significantly in 8 mmol nec-1 group than that of the control group（P〈0.05）. Conclusions Nec-1 can inhibit neurotoxicity and relieve the impact on cognitive ability; and could lower the expression of mGluR1 genes and protein.