目的 探讨补阳还五汤对卒中后抑郁大鼠海马区细胞周期蛋白1(Cyclin D1)、细胞周期蛋白依赖性激酶2(Cdk2)的影响.方法 运用大脑中动脉局灶性永久性线栓法结合慢性不可预见温和应激及孤养法制备大鼠卒中后抑郁模型,将实验动物随机分为五组:假手术组、缺血性脑卒中组、卒中后抑郁组、卒中后抑郁±氟西汀组(以下简称氟西汀组)和卒中后抑郁±补阳还五汤组(以下简称补阳还五汤组),分别给予不同的处理,在7d,14d,21d不同时间点处死动物,观察海马区神经细胞的形态改变,并运用免疫组织化学方法检测Cyclin D1、Cdk2的表达.结果 缺血性脑卒中组和模型组大鼠与假手术组相比,海马区神经细胞出现退化、变性、坏死等病理改变,细胞凋亡数量增加;在正常大鼠海马区神经细胞内,处理后7、14、21 d Cyclin D1的表达阳性率分别为(1.16±0.34)%、(1.62±0.29)%和(1.60±0.24)%,Cdk2在各时间点的表达阳性率分别为(1.52±0.26)%、(1.85±0.23)%和(1.97±0.10)%;卒中后抑郁组海马区Cyclin D1和Cdk2表达均上调,Cyclin D1在各时间点分别是(49.69±5.68)%、(58.17±2.89)%和(50.87±2.48)%,Cdk 2在各时间点分别是(50.63±2.93)%、(70.34±1.47)%和(61.35±3.04)%;而与模型组比较,氟西汀组、补阳还五汤组表达则下调,氟西汀组Cyclin D1在各时间点分别是(16.62±4.27)%、(29.66±5.24)%和(26.71±1.32)%,氟西汀组Cdk2在各时间点分别是(18.05±2.26)%、(33.84±3.12)%和(24.51±2.66)%,补阳还五汤组Cyclin D1在各时间点分别是(14.62±2.06)%、(26.89±3.41)%和(23.68±2.01)%,补阳还五汤组Cdk2在各时间点分别是(16.60±2.42)%、(20.09±3.45)%和(22.19±1.70)%.结论 脑缺血性卒中后抑郁Cyclin D1和Cdk2的异常表达可能诱发了神经细胞的死亡,补阳还五汤可能是通过抑制Cycli
Objective To observe the effects of Buyang Huanwu decoction(BYHW) on the expression of Cyclin D1 and Cdk2 in rats with post-stroke depression(PSD).Methods The rats model of focal cerebral ischemia was established by means of middle cerebral artery occlusion(MCAO).Then three weeks of salute-living and chronic unpredictable mild stress(CUMS) was given to the animal after cerebral stroke to induce the post-stoke depression animal model.The rats were divided into 5 groups:the sham operated group,the midge cerebral artery occlusion(MCAO) group,the PSD group,the fluoxetine group and the BYHWD group.The rats were subjected to left MCAO rebuilding in consistent focal cerebral ischemia,followed by an 21-day exposure to chronic mild stress (CMS)and single housing to induce PSD animal model.All rats were killed in 7,14 and 21 day after operation.The expressions of Cyclin D1 and Cdk2 were measured by immunohistochemical staining.Results Pathological changes such as hippocampal nerve cell regression,degeneration and necrosis were observed in the model rats compare with the sham operated group.The expression of Cyclin D1 in normal hippocampus in 7,14 or 21 day after operation was (1.16±0.34)%,(1.62±0.29)% and (1.60±0.24)% respectively,and Cdk2 was (1.52±0.26)%,(1.85±0.23)% and (1.97±0.10)%.After PSD the expression of Cyclin D1 was (49.69±5.68)%,(58.17± 2.89) % and (50.87 ± 2.48) % respectively,and Cdk2 was (50.63 ± 2.93) %,(70.34± 1.47) % and (61.35 ± 3.04) %.Compared with model group,Fluoxetine and BYHW significantly reduced the numbers of Cyclin D1 and Cdk2 positive cells,the expression of Cyclin D1 was (16.62±4.27)%,(29.66±5.24)% and (26.71±1.32)% at fluoxetine group,and Cdk2 was (18.05±2.26) %,(33.84±3.12) % and (24.51±2.66) %.The expression of Cvclin D1 was (14.62±2.06)%,(26.89±3.41)% and (23.68±2.01)% at BYHWD group,and Cdk2 was (16.60± 2.42) %,(20.09±3.45) % and (22.19± 1.70)