肌苷对阿尔茨海默病模型大鼠认知功能改善作用及机制研究

Effects and mechanism of inosine on cognitive function of Alzheimer＇s disease model in rats

目的研究肌苷对β-淀粉样蛋白1-40（beta—amyloidprotein，Aβ1-40）所致的模拟阿尔茨海默病大鼠神经元凋亡及Bel-2和Bax表达的影响。方法成年健康雄性Wistar大鼠30只，用随机数字表法随机分为对照组、模型组和治疗组各10只，经左侧侧脑室微量注射Aβ1-40建立阿尔茨海默病模型，腹腔注射肌苷（100mg·kg^-1）干预治疗，采用Y型电迷宫检测大鼠学习和记忆功能，HE染色观察神经细胞的结构变化，原位TUNEL法检测神经细胞凋亡，免疫组织化学检法测Bel-2和Bax蛋白表达。结果模型组大鼠认知能力[（79．84±6．46）次，（4．83±3．14）次]较对照组[（59．13±7．52）次，（7．94±2．21）次]明显下降（t=5．67，2．25，P〈0．05），神经细胞结构异常，TUNEL阳性细胞数明显增多、Bcl-2和Bax蛋白表达增加（P〈0．05）。肌苷组大鼠认知能力[（68．54±8．86）次，（7.11±1．13）次]和细胞结构较模型组[（81．22±3．92）次，（4．61±1．61）次]显著改善（t=3．46，4．64，P〈0．05），相对于模型组（20．24±1．32，41．82±3．71，35．51±2．30），肌苷组Bcl-2蛋白表达（33．52±5．68）明显增强、Bax蛋白表达（25．11±2．45）明显减弱、细胞凋亡数量（23．40±7．07）明显减少（t=6．04，9．94，4．30，P〈0．05）。结论肌苷能促进Bel-2表达、抑制Bax表达，降低凋亡率，从而改善阿尔茨海默病大鼠大学习和记忆能力。

Objective To investigate the effect of inosine on the neuronal apoptosis and the expressions of Bcl-2 and Bax in Alzheimer＇ s disease（AD） model in rats induced with beta-amyloid proteinl-40 （Aβ1-40 ） injection,and to explore some mechanism of inosine in improving the capability of learning and memory. Methods Thirty adult healthy male wistar rats were randomly divided into control group （n = 10） ,model group （n = 10） and treated group （n= 10）. The AD models were established by injecting Aβ1-40 stereotactically into the left Lateral ventricle,and treated by injecting inosine （ 100mg.kg^-1 ） intraperitoneally. The learning and memory capacity of rats was evaluated with Y-electric maze. HE staining was used to observe the structure. The neuronal apoptosis was investigated by TUNEL assay. The expressions of Bcl-2 and Bax were determined with immunohistochemistry assay. Results Compared with control group （59.13 ± 7.52,7.94 ± 2.21 ）, the model group rats showed disorder cognitive ability（79.84 ± 6.46,4.83 ± 3.14） and abnormal cell structure （ t = 5.67,2.25 P 〈 0.05 ）. The number of neuronal apoptosis and the expressions of Bcl-2 and Bax protein increased significantly than those in control group （ P 〈 0. 05 ）. Compared with model group （ 81.22 ± 3.92,4.61 ± 1.60 ）, inosine improved strikingly cognitive ability（68.54 ± 8.86,7.14 ±1.13 ） and cell structure （ t = 3.46,4.64, P 〈 0.05 ）. The expressions of Bcl-2 （ 33.52 ± 5.68） increased and Bax （ 25. 11 ± 2.45 ） while the number of neuronal apoptosis （ 23.40 ± 7.07 ） decreased markablely than those（20.24 ± 1.32,41.82 ± 3.71,35.51 ± 2.30） in model group （ t = 6.04,9.94,4.30 P 〈 0.05）. Conclusion Inosine might decrease the neuronal apoptotic rate by enhancing Bcl-2 and inhibiting Bax expressions,which improve learning and memory capacity of AD rats.