|
|
|
| Effects of 3-n-butylphthalide on memory and Caspase-3 expression in the hippocampal CA1 region of vascular dementia rats |
| MAO Xijing ZHU Bochi YU Tingmin YAO Gang▲ |
| Department of Neurology, the Second Hospital of Jilin University, Jilin Province, Changchun 130041, China |
|
|
|
|
Abstract Objective To study the effects of 3-n-butylphthalide (NBP) on memory and Caspase-3 expression in the hippocampal CA1 region of vascular dementia rats, in order to explore protective effects and mechanisms of NBP on rats with vascular dementia (VD). Methods A total of 80 SPF Wistar rats were divided into vascular dementia models group (VD group), vascular dementia models + NBP injection group (NBP treatment group), sham surgery + NBP injection group (NBP control group), sham surgery group (Sham group), according to random group method. Then each group was divided into four subgroups (n = 5): 1, 2, 4, and 8 weeks after surgery. VD models were established by ligating bilateral common carotid artery. Then the rats in the NBP treatment group and NBP control group were intraperitoneally injected with NBP 5 mg/（kg·d） for 7 consecutive days. The rats in the VD group and Sham group were intraperitoneally injected with saline (0.2 mL/d) for 7 consecutive days. Memory ability of 8 weeks subgroup rats were tested by Morris water maze at 4 and 8 weeks after surgery. At 1, 2, 4, and 8 weeks after surgery, the rats in each group were decapitated. The brains were obtained, and then hippocampus were isolated. Caspase-3 expression in the hippocampal CA1 region were determined by immunohistochemistry. Results Compared with VD group, escape latency in the NBP treatment group were significantly shorter (P < 0.05). At 1, 2, 4 and 8 weeks after surgery, Caspase-3 expression in the VD group and NBP treatment group were significantly increased than those in the Sham group (P < 0.05). Compared with VD group, Caspase-3 expression in the NBP treatment group were significantly lower at 4 and 8 weeks after surgery (P < 0.05). In VD group, Caspase-3 expression at 8 weeks after surgery was significantly higher than at 1 weeks (P < 0.05). Conclusion NBP can improve the memory ability of VD rats, which may be connected with the overexpression of caspase-3 in the hippocampus CA1 region of VD rats.
|
|
|
|
|
|
[1] 朱以诚，崔丽英，高山，等.丁苯酞注射剂治疗急性脑梗死的多中心、随机、双盲双模拟、对照Ⅲ期临床试验[J].中华神经科杂志，2014，2：113-118.
[2] 程文姚，杨健，余新沛.丁苯酞软胶囊与尼莫地平对卒中后血管性痴呆患者的疗效[J].解放军预防医学杂志，2016， 34（4）：516-518.
[3] Huai Y，Dong Y，Xu J，et al. L-3-n-butylphthalide protects against vascular dementia via activation of the Akt kinase pathway [J]. Neural Regen Res，2013，8（19）：1733-1742.
[4] Zhang L，Lü L，Chan WM，et al. Effects of DL-3-n-butylphthalide on vascular dementia and angiogenesis [J]. Neurochem Res，2012，37（5）：911-919.
[5] 赵万红，罗超，龚应霞，等.消旋丁苯酞对慢性脑缺血大鼠认知功能的影响及其生化机制研究[J].中华老年医学杂志，2014，33（4）：412-415.
[6] Sun Zk，Ma XR，Jia YJ，et al. Effects of resveratrol on apoptosis in a rat model of vascular dementia [J]. Exp Ther Med，2014，7（4）：843-848.
[7] Shen Yang，Guangan Zhou，Hong Liu，et al. Protective effects of p38 MAPK inhibitor SB202190 against hippocampal apoptosis and spatial learning and memory deficits in a rat model of vascular dementia [J]. Biomed Res Int，2013， 2013：215798.
[8] 毛德文，陈月桥，王丽，等. Caspase-8及Caspase-3与细胞凋亡[J].辽宁中医药大学学报，2008，10（10）：148-150.
[9] Abdel Shakor AB，Atia M，Alshehri AS，et al. Ceramide generation during curcumin-induced apoptosis is controlled by crosstalk among Bcl-2，Bcl-xL，caspases and glutathione [J]. Cell Signal，2015，27（11）：2220-2230.
[10] Delgado ME，Olsson M，Lincoln FA，et al. Determining the contributions of caspase-2，caspase-8 and effector caspases to intracellular VDVADase activities during apoptosis initiation and execution [J]. Biochim Biophys Acta，2013，1833（10）：2279-2292.
[11] Jia H，Zhang XM，Zhang BA，et al. Dendritic morphology of neurons in medial prefrontal cortex and hippocampus in 2VO rats [J]. Neurol Sci，2012，33（5）：1063-1070.
[12] Cechetti F，Worm PV，Pereira LO，et al. The modified 2VO ischemia protocol causes cognitive impairment similar to that induced by the standard method，but with a better survival rate [J]. Braz J Med Biol Res，2010，43（12）：1178-1183.
[13] Zhong XM，Ren XC，Lou YL，et al. Effects of in-vitro cultured calculus bovis on learning and memory impairments of hyperlipemia vascular dementia rats [J]. J Ethnopharmacol，2016，192：390-397.
[14] Edgington-Mitchell LE，Bogyo M. Detection of active caspases during apoptosis using fluorescent activity-based probes [J]. Methods Mol Biol，2016，1419：27-39.
[15] Lu HF，Chen YS，Yang JS，et al. Gypenosides induced G0/G1 arrest via inhibition of cyclin E and induction of apoptosis via activation of caspases-3 and -9 in human lung cancer A-549 cells [J]. In Vivo，2008，22（2）：215-221.
[16] Hayakawa A，Kawamoto Y，Nakajima H，et al. Bid truncation mediated by caspases-3 and -9 in vinorelbine-induced apoptosis [J]. Apoptosis，2008，13（4）：523-530.
[17] Katunuma N，Ohashi A，Sano E，et al. Catechin derivatives：specific inhibitor for caspases-3，7 and 2，and the prevention of apoptosis at the cell and animal levels [J]. FEBS Lett，2006，580（3）：741-746.
[18] Morales-Cano D，Calvio E，Rubio V，et al. Apoptosis induced by paclitaxel via Bcl-2，Bax and caspases 3 and 9 activation in NB4 human leukaemia cells is not modulated by ERK inhibition [J]. Exp Toxicol Pathol，2013，65（7-8）：1101-1108. |
|
|
|
