地佐环平对糖尿病伴抑郁大鼠抑郁样行为及海马神经元损伤的作用  

Effects of MK801 on the depression-like behaviors and damaged hippocampus in diabetes with de-pression rats

作　　者：杨蕙[1] 刘林[1] 杜青[2] 李薇[1] 赵洪庆[2] 刘检[1] 孟盼[2] 王宇红[1] 

机构地区：[1]湖南中医药大学第一附属医院中心实验室,长沙410007 [2]湖南中医药大学湖南省中药粉体与创新药物省部共建国家重点实验室培育基地,长沙410007

出　　处：《中华行为医学与脑科学杂志》2017年第8期684-688,共5页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：基金项目：国家自然科学基金项目（81403379,81573965,81603604）;湖南省中药粉体与创新药物省部共建国家重点实验室培育基地开放基金项目（ZYFT201502）

摘　　要：目的探讨地佐环平（dizocilpine，MK801）对糖尿病并发抑郁症大鼠抑郁样行为及海马神经元损伤的影响。方法建立糖尿病并发抑郁症大鼠模型，并采用随机数字表将其随机分为2组：模型组、MK801组，以健康SD大鼠为正常对照组，每组6只。采用旷场实验检测大鼠行为学，采用HE染色检查大鼠海马病理损伤；采用尼氏染色，检测大鼠海马神经元中的凋亡小体数目；采用TUNEL染色，观察大鼠海马神经元凋亡；采用免疫荧光法，测定Bax、Bcl-2凋亡蛋白的表达。结果与正常组比较，模型组大鼠海马活动次数显著减少，海马神经元空泡、尼氏小体减少、凋亡细胞增多，凋亡蛋白Bax表达显著增加（94．57±7．97，30．08±5．73，P〈0．01）而Bcl-2表达减少（24．65±5．26，57．93±7．85，P〈0．01）。与模型组比较，地佐环平组大鼠活动次数显著增加[（12．50±4．42）次，（5．17±2．04）次，P〈0．01]，海马病理损伤减轻，尼氏小体表达显著增加（133．55±16．74，67．51±19．32，P〈0．01）而凋亡细胞数量显著减少（22．50±6．35，42．00±6．20，P〈0．01），凋亡蛋白Bax表达减少而Bcl-2表达增加（33．00±4．57，24．65±5．26，P〈0．01）。结论地佐环平可能通过影响凋亡蛋白的表达，发挥保护糖尿病并发抑郁症大鼠海马神经元损伤的作用。Objective To investigate the effects of dizocilpine（ MK801 ） on depressive-like behav- iors and damaged hippocampus in rats with diabetes-related depression.Methods The animal models of dia- betes-related depression were established and they were randomly divided into two groups based on random number table： model group and MK801 group,while 6 rats were included in each group. And another six health rats were regarded as control group. The Open-field test was used to detect the activities. The damage of hippocampus was valued by HE staining, Nissl staining, and Tunel staining. The protein expressions of Bax, Bcl-2 in hippocampus were detected by Western blot.Results The number of activities was significant decreased in Open-field test in model group when compared with control. Hippocampal neurons vacuoles, Nissl bodies were decreased and apoptotic cells were increased in hippocampus in model group as well. Fur- thermore,the expression of Bax was significant up-regulated（94.57±7.97 ,P〈0.01）, while the Bcl-2 was de- clined（24.65±5.26,P〈0.01 ）. Compared with the model group, the animals in MK801 group exhibited in- creased activities （ 12.50±4.42, P〈0.01 ）, which accompany with an increased Nissl body （ 133.55 ± 16.74, P〈 0.01） and a decreased apoptosis（22.50±6.35,P〈0.01）. Moreover,the expression of Bax was decreased andthe Bcl-2 was increased in MK801 group when they were contrasted to model（33.00±4.57,P〈0.01 ）. Conclusion MK801 is a significant element to regulate the expression of apoptosis protein including Bax, Bcl-2, and to protecte the hippocampal neuron in rats with diabetes-related depression effectively.

关 键 词：糖尿病并发抑郁症 地佐环平 海马 凋亡 

分 类 号：R587.1[医药卫生—内分泌] R749.4[医药卫生—内科学]