楮实提取物改善老年性痴呆复合模型大鼠空间学习记忆能力及机制研究

目的 观察Aβ25-35联合D-半乳糖诱导大鼠新型复合老年性痴呆模型空间学习记忆能力及中药楮实提取物的干预作用;探讨楮实提取物可能的作用机制.方法 双侧海马内一次性注射Aβ25-35,联合长期颁部皮下注射D-半乳糖制作大鼠AD动物模型,手术造模后开始给予中药楮实提取物灌胃干预,连续30d.以Morris水迷宫实验检测大鼠空间学习记忆能力变化,免疫组织化学法检测内质网应激标志蛋白BiP(葡萄糖调节蛋白78-GRP78)、PERK与CHOP表达水平.结果 Aβ25-35联合D-半乳糖诱导大鼠新型复合老年性痴呆模型空间学习记忆能力障碍逃避潜伏期为(20.90±9.16)s,原平台象限比为(11.05±4.43)%],BiP表达水平平均灰度值(139.71±3.47)]降低,PERK及CHOP表达水平平均灰度值分别为(97.96±5.97)、(110.93±4.91)]升高.中药楮实提取物组逃避潜伏期(5.41±3.47)s]缩短,原平台象限比(48.28±7.03)%]增加,BiP表达水平平均灰度值(121.17±4.76)]升高,PERK及CHOP表达水平平均灰度值分别为(122.11±4.73)、(123.34±7.73)]降低,与模型组比较差异显著(P＜0.05～0.01).结论 Aβ25-35联合D-半乳糖可成功诱导建立大鼠复合损伤AD模型,中药楮实提取物对该模型大鼠空间学习记忆能力具有显著改善作用,机制可能与内质网应激及其激活的细胞凋亡通路相关.

Effect of Broussonetia papyrifera ( L. ) Vent aqueous extract on the ability of space learning and memory in the rats complex model of Alzheimer's disease

Objective To observe the effect of aqueous extract of Broussonetia papyrifera ( L. ) Vent on the ability of space learning and memory in the rats with Alzheimer' s disease (AD) induced by Aβ 25-35 and Dgalactose and to explore the mechanisms underlying those improvements. Methods The animal model of AD was established by Aβ 25-35 stereotactic injection into the hippocampus of rats in 5 minutes,while long-term intraperitoneal injection with D-gal. After the injection of Aβ25-35,rats were treated with aqueous extract of Broussonetia papyrifera ( L. ) Vent for the next 30 days. Morris water maze with computer system and the spatial exploration experiments were used to assess the behavior performances of the rats. Immunohistochemical technique was used to detect the expression of BiP, PERK and CHOP. Results The ability of space learning and memory of rats complex model of Alzheimer's disease induced by Aβ25-35 and D-gal was damaged,while escape latency was (20.90± 9.16 ) s,and the proportion of original platform quadrant was ( 11.05 ± 4.43 ) %. The expression level of Bip was reduced ,while the mean gray was ( 139.71 ± 3.47 ). The expression level of PERK and CHOP was increased,while the mean gray were (97.96 ± 5.97 ), ( 110.93±4.91 )separately. The escape latency of rats in the aqueous extract of Broussonetia papyrifera ( L. ) Vent treated groups was ( 5.41 ± 3.47 ) s and shorter than the model group,while the proportion of original platform quadrant was (48.28 ± 7.03 )% and higher than the model group.The expression level of Bip in the treated group was higher than the model group, while the mean gray were ( 121.17 ±4.76). The expression level of PERK and CHOP in the treated group was lower than the model group,while the mean gray were ( 122.11 ± 4.73 ), ( 123.34 ± 7.73 ) separately. Significant differences were observed between model group and aqueous extract of Broussonetia papyrifera ( L. ) Vent treated groups (P＜ 0. 05 ～ 0. 01 ).Conclusion Aqueous extract of Broussonetia papyrifera ( L. ) Vent can improve learning and memory disorders of the model rats induced by Aβ25-35 and D-galactose. ER (endoplasmic reticulum) stress and correlated apoptosis pathway might be involved in the underlying mechanisms.