竹节参总皂苷通过减轻成纤维细胞生长因子21抵抗改善自然衰老大鼠的认知功能障碍  

Saponins of Panax Japonicus Improve Cognitive Dysfunction in Naturally Aged Rats by Attenuating FGF21 Resistance

作　　者：岳博文 倪露 郑莹 胡凡馨 杨啟巧 袁成福[1] 袁丁[1] 王金娥 周志勇[1] YUE Bowen;NI Lu;ZHENG Ying;HU Fanxin;YANG Qiqiao;YUAN Chengfu;YUAN Ding;WANG Jin’e;ZHOU Zhiyong(Third-grade Pharmacological Laboratory on Traditional Chinese Medicine Approved by State Administration of Traditional Chinese Medicine,Medical College of China Three Gorges University,Yichang 443002 Hubei,China)

机构地区：[1]国家中医药管理局中药药理三级实验室,三峡大学医学院,湖北宜昌443002

出　　处：《中药新药与临床药理》2023年第5期605-612,共8页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：湖北省自然科学基金创新群体项目(2021CFA015)。

摘　　要：目的探讨竹节参总皂苷对自然衰老大鼠认知功能障碍的改善作用及其相关机制。方法将40只18月龄SD雄性大鼠随机分为模型组、竹节参总皂苷低剂量组、竹节参总皂苷高剂量组、亚精胺组,另取10只5月龄雄性SD大鼠作为对照组。竹节参总皂苷低、高剂量组大鼠分别给予含有药物的混合饲料(给药剂量为10、30 mg·kg^(-1)),亚精胺组大鼠自由饮用含亚精胺的饮用水(浓度为1 mmol·L^(-1)),连续给药4个月。采用Morris水迷宫实验评价大鼠认知功能;HE染色法检测皮层及海马神经元的病理变化;Nissl染色法检测皮层及海马神经元尼氏体的变化;透射电镜检测皮层线粒体超微结构的变化;Western Blot法检测皮层及海马组织成纤维细胞生长因子21(FGF21)-FGFR1/β-Klotho信号通路相关蛋白的表达。结果与对照组比较,模型组大鼠的逃避潜伏期显著延长(P<0.01),目标平台穿越次数、目标象限停留时间均显著减少(P<0.01),首次到达目标平台路程显著增加(P<0.01);神经元损伤明显,尼氏体数目降低,神经元线粒体出现空泡化,嵴排布紊乱;大鼠皮层及海马组织中FGF21蛋白表达水平显著升高(P<0.01),FGFR1、β-klotho、P-ERK蛋白表达水平明显降低(P<0.05,P<0.01)。与模型组比较,竹节参总皂苷高剂量组大鼠的逃避潜伏期明显缩短(P<0.05),目标平台穿越次数、目标象限停留时间均显著增加(P<0.01),首次到达目标平台路程显著减少(P<0.01);竹节参总皂苷低、高剂量组大鼠的神经元损伤明显减轻,尼氏体数目增加,线粒体空泡化、嵴排布紊乱现象消失;皮层及海马组织中FGF21蛋白表达水平显著降低(P<0.01),P-ERK、FGFR1、β-klotho蛋白表达水平明显升高(P<0.05,P<0.01)。结论竹节参总皂苷能有效改善自然衰老大鼠的认知功能障碍,可能与通过FGF21-FGFR1/β-klotho信号通路减轻FGF21抵抗,并改善神经元线粒体结构损伤有关。Objective To investigate the effects and related mechanisms of saponins of Panax Japonicus(SPJ)on the improvement of cognitive function in naturally aged rats.Methods Forty 18-month-old male SD rats were randomly divided into the model group,the low-and high-dose of SPJ groups and the spermidine group,and ten 5-month-old male SD rats were taken as the control group.The rats in the low-and high-dose of SPJ groups were given a mixed diet containing the drug(administered at 10 and 30 mg·kg^(-1)),and the rats in the spermidine group were given drinking water containing spermidine(at a concentration of 1 mmol·L^(-1))and libitum for 4 consecutive months.The cognitive functions of the rats were evaluated by Morris water maze test;the pathological changes of cortical and hippocampal neurons were detected by HE staining;the changes of Nissl bodies of cortical and hippocampal neurons were detected by Nissl staining;the ultrastructural changes of mitochondria in the rat cortex were detected by transmission electron microscopy;the expression of FGF21-FGFR1/β-Klotho signaling pathway related proteins in cortex and hippocampus was detected by Western Blot.Results Compared with the control group,the escape latency of the model group was significantly prolonged(P<0.01),the crossing times of the target platform and the stay time in the target quadrant were significantly decreased(P<0.01),and the distance to the target platform for the first time was significantly increased(P<0.01).The neuron damage was obvious,the amount of Nissl bodies decreased,the neuronal mitochondria showed vacuolization and crest arrangement disorder.The protein expression of FGF21 in cortex and hippocampus was significantly increased,while the protein expression levels of FGFR1,β-klotho and P-ERK were significantly decreased(P<0.05,P<0.01).Compared with the model group,the escape latency of rats in the high-dose of SPJ group was significantly shortened(P<0.05),the crossing times of the target platform and the stay time in the target quadrant were signi

关 键 词：竹节参总皂苷 自然衰老 认知功能障碍 FGF21-FGFR1/β-klotho信号通路 成纤维细胞生长因子21抵抗 大鼠 

分 类 号：R285.5[医药卫生—中药学]