白肉灵芝水提物改善衰老大鼠认知功能的作用  

Effect of the aqueous extracts of ganoderma leucocontextum on cognitive function of aging rats

作　　者：王昱[1,2] 秦序 何九军[1,2] 王逸璇 WANG Yu;QIN Xu;HE Jiu-jun;WANG Yi-xuan(Department of Biology,College of Agriculture and Forestry,Gansu Chengxian 742500,China;Center for Research and Development of Longnan Characteristic Agro-Bioresources,Longnan Teachers College,Gansu Chengxian 742500,China;Department of Food Science and Engineering,College of Food Science and Engineering,Gansu Agricultural University,Lanzhou 730070,China)

机构地区：[1]陇南师范高等专科学校农林技术学院生物系,甘肃成县742500 [2]陇南特色农业生物资源研究开发中心,甘肃成县742500 [3]甘肃农业大学食品科学与工程学院食品科学与工程系,兰州730070

出　　处：《解剖学报》2022年第6期711-718,共8页Acta Anatomica Sinica

基　　金：甘肃省高等学校科研基金(2015B-148);甘肃省陇南市科技计划基金(2019-ZD-10);陇南特色农业生物资源研究开发中心基金(LNSZYFZX202102)。

摘　　要：目的 探讨白肉灵芝水提物(GLAE)改善衰老大鼠认知功能的作用及机制。方法 将50只健康大鼠分成对照组、模型组、GLAE低剂量组、GLAE中剂量组和GLAE高剂量组,用D-半乳糖构建衰老SD大鼠模型,同时分别给予不同剂量的(0、50、100和200 mg/kg)GLAE处理,采用新物体认知和跳台实验方法检测大鼠认知功能的改变,甲苯胺蓝、吉姆萨和HE染色进行病理学观察,彗星电泳检测大脑细胞DNA的损伤,ELISA、Western blotting和Real-time PCR法检测大脑组织蛋白激酶A(PKA)/环磷酸腺苷(cAMP)反应元件结合蛋白(CREB)信号通路相关因子表达。结果 与模型组比较,GLAE干预后,大鼠认知功能衰退及大脑皮层病理变化有显著改善,大脑细胞DNA损伤程度显著降低(P<0.05),大脑组织cAMP、脑源性神经生长因子(BDNF)和神经生长因子(NGF)含量显著增高(P<0.01,P<0.05),PKA、BDNF、NGF和CREB mRNA及PKA、BDNF、NGF和CREB蛋白的表达水平显著上升(P<0.01,P<0.05)。结论 GLAE可改善衰老大鼠的认知功能,其机制可能与其激活大脑PKA/CREB信号通路,增加神经营养因子含量,抑制大脑细胞DNA损伤有关。Objective To investigate the effects of the aqueous extracts of ganoderma leucocontextum(GLAE) on cognitive decline of aging rats and possible regulation mechanism. Methods Fifty rats were divided into five groups, control group, model group, GLAE low-dose group, GLAE middle-dose group and GLAE high-dose group. Aging SD rat models were made by D-galactose, and then treated continuously with different doses(0, 50, 100, 200 mg/kg) of GLAE. The novel object recognition and step down test were performed to detect the changes of rats cognitive function. The brain tissue was stained with toluidine blue, Giemsa and HE staining and observed. The cerebral cell DNA damage was detected by comet assay. Expressions of protein kinase A(PKA)/cyclic adenosine monophosphate(cAMP)-response element binding protein(CREB) signaling pathway related factors in brain were respectively detected by ELISA, Western blotting and Real-time PCR. Results Compared with the model group, administration of GLAE could obviously alleviate rats cognitive decline and pathological change. The levels of cell DNA damage reduced markedly(P<0.05). The contents of cAMP, brain derived neurotrophic factor(BDNF) and nerve growth factor(NGF), and also expression levels of mRNA and protein of PKA, BDNF, NGF, CREB in the brain increased significantly in each medicated group(P<0.01, P<0.05). Conclusion GLAE can improve cognitive function, and its mechanism may be related to activation of brain PKA/CREB signaling pathway, increase in neurotrophic factor content and inhibition of cell DNA damage.

关 键 词：白肉灵芝水提物 D-半乳糖 认知功能 蛋白激酶A/环磷酸腺苷反应元件结合蛋白信号通路 免疫印迹法 衰老大鼠 

分 类 号：R741[医药卫生—神经病学与精神病学]