雷公藤红素对肝叶部分切除老年小鼠术后认知功能及海马Tau蛋白磷酸化的影响

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (8): 841-846.

• 基础研究 • 下一篇

雷公藤红素对肝叶部分切除老年小鼠术后认知功能及海马Tau蛋白磷酸化的影响

葛叶盈¹, 万燕杰², 徐静², 孟凡珍³

¹宁波市第六医院麻醉科,宁波 315040,浙江;
²上海市浦东新区公利医院麻醉科,浦东 200135,上海;
³连云港市第二医院麻醉科,连云港 222001,江苏

收稿日期:2010-05-24 修回日期:2010-08-12 出版日期:2010-08-26 发布日期:2020-09-17
通讯作者: 万燕杰,男,主任医师,硕士生导师,研究方向:术后认知功能障碍。Tel: 021-58517146 E-mail: yanjie.wan@yahoo.com.cn
作者简介:葛叶盈,女,硕士,副主任医师,研究方向:术后认知功能障碍。Tel: 136065846928 E-mail: geyeying59198@163.com
基金资助:
上海市浦东新区科委重点学科资助项目(PWZXK2007-11);上海市浦东新区社发局科研资助项目(PW2007A-13)

Effect of Celastrol on cognitive function and Tau hyperphosphorylation in eldly mice hippocampus after partial hepatectomy

GE Ye-ying¹, WAN Yan-jie², XU Jing², MENG Fan-zhen³

¹Department of Anesthesia, Ningbo 6^th Hospital, Ningbo 315040, Zhejiang,China;
²Department of Anesthesiology, Gongli Hospital, Pudong, Shanghai 200135, China;
³Department of Anesthesia, Lianyungang 2^nd Hospital, Lianyungang 222001, Jiangsu,China

Received:2010-05-24 Revised:2010-08-12 Online:2010-08-26 Published:2020-09-17

摘要/Abstract

摘要： 目的: 观察肝叶部分切除术后老年小鼠认知功能的变化及海马内Tau蛋白磷酸化位点Ser396、Ser199/202的变化和雷公藤红素对老年小鼠术后认知功能障碍时的神经保护作用。方法: C57BL/6老年小鼠随机分为3组(n =48):假手术组 (S组) 、肝叶部分切除术组 (O组)和肝叶部分切除术加雷公藤红素组(C组)。每组再根据不同时间点分为 12 h、1 d、3 d 和7 d 4 个亚组,每个时间点12只动物。三组小鼠采用Morris水迷宫检测小鼠认知功能,免疫组织化学法和Western blotting方法检测各组小鼠海马Tau蛋白磷酸化的变化。结果: 与S组同时点比较,O组术后3 d和7 d时水迷宫成绩下降( P<0.05);C组术后 3 d 和 7 d 水迷宫成绩好于O组(P<0.05),而与S组接近(P>0.05)。免疫组织化学染色阳性数和Western blotting显示O组Tau蛋白磷酸化位点Ser396、Ser199/202表达多于S组(P<0.01 ),而C组表达少于O组 (P<0.01),与S组接近(P>0.05)。结论: 雷公藤红素对老年小鼠肝叶部分切除术造成的认知功能障碍具有明显的保护作用,其机制可能与抑制Tau蛋白异常磷酸化有关。

关键词: 肝叶部分切除术, Tau蛋白, 磷酸化, 认知功能, 雷公藤红素

Abstract: AIM: To observe the expression of Tau phosphorylation in hippocampus and cognitive function deficit on eldly mice induced by partial hepatectomy. As well as the neuroprotective effect of Celastrol on postoperative cognitive dysfunction.METHODS: The C57BL/6 eldly mice were randomly assigned to three groups (n =48): Sham operation group (group S),operation group (group O) underwent partial hepatectomy and the Celastrol treatment was given to the operation group (group C). According to the different time point,each group(n=12) was divided 12 h,1,3 and 7 d,respectively. The cognitive function in three groups was detected by Morris water maze test;the changes of Tau phosphorylation were measured by immunocytochemistry/Western blotting.RESULTS: Compared with the Group S, the results of the Morris water maze test were significantly decreased in Group O at 3, 7 d (P<0.05); compared with Group O,the results of the Morris water maze test in Group C were obviously increased (P<0.05), approached the Group S (P>0.05). Compared with Group S,the immunochemistry staining of brain slice and Western blotting showed that the expressions of Tau pSer404, pSer199/202 in Group O were markedly increased (P<0.01). The level of Tau hyperphosphorylation in Group C was markedly decreased comparing to those in Group O (P<0.01) and approached the Group S (P>0.05).CONCLUSION: Celastrol can improve cognitive dysfunction induced by partial hepatectomy in eldly mice, the mechanism is correlated with Tau hyperphosphorylation inhibited.

Key words: Partial hepatectomy, Tau protein, Phosphorylation, Cognitive function, Celastrol

中图分类号:

R965.2

葛叶盈, 万燕杰, 徐静, 孟凡珍. 雷公藤红素对肝叶部分切除老年小鼠术后认知功能及海马Tau蛋白磷酸化的影响[J]. 中国临床药理学与治疗学, 2010, 15(8): 841-846.

GE Ye-ying, WAN Yan-jie, XU Jing, MENG Fan-zhen. Effect of Celastrol on cognitive function and Tau hyperphosphorylation in eldly mice hippocampus after partial hepatectomy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(8): 841-846.

参考文献

[1] Guillozet AL,Weintraub S,Mash DC,et al.Neurofibrillary tangles.amyloid,and memory in aging and mild cognitive impairment[J].Arch Neurol,2003,60(5):729-736.
[2] Hyo WJ,Yoo SC,Yoon SK,et al.Celastrol inhibits production of nitric oxide and proinflammatory cytokines through MAPK signal transduction and NF-κB in LPS-stimulated BV-2 microglial cells[J]. Exp Mol Med,2007,39(6):715-721.
[3] 张艳,贾丹辉,刘宗文,等.雷公藤对大鼠局灶性脑缺血再灌注损伤的保护作用[J].中国新药与临床杂志,2005,24(5):862-864.
[4] 吴周全,万燕杰,曾因明,等.肝部分切除术后大鼠认知功能及β淀粉样蛋白的变化[J].中华麻醉学杂志,2008,28(4):334-336.
[5] Tian Q,Wang J. Role of serine/threonine protein phosphatase in Alzheimer's disease[J]. Neurosignals,2002,11(5):262-269.
[6] Wan YJ,Xu J,Ma DQ,et al. Postoprative impairment of cognitive function in rats-Apossible role for cytokine-mediated inflammation in the hippocampus[J]. Anesthesiology,2007,107(5):436-443.
[7] 段立晖,周国庆,夏树开,等.β淀粉样蛋白诱导大鼠海马神经元Tau蛋白异常磷酸化及雌激素的保护作用[J].医学研究生学报,2008,21(5):486-490.
[8] Tuppoa EE,Ariasb HR.The role of inflammation in Alzheimerps disease[J].Int J Biochem Cell Biol,2005,37(5):289-305.
[9] Li YK,Liu L,Barger SW,et al.Interleukin-1 mediates pathological effects of microglia on Tau phosphorylation and on synap tophysin synthesis in cortical neurons through a p38-MAPK pathway[J].J Neurosci,2003,23(5):1605-1611.
[10] 黄秀旺,许建华,陈元仲.雷公藤内酯醇在大鼠体内的组织分布[J].中国临床药理学与治疗学,2008,13(7):764-767.
[11] Allison AC,Cacabelos R,Lombardi VR,et al. Celastrol,a potent antioxidant andanti-inflammatory drug, as a possible treatment for Alzheimer's disease[J]. Prog Neuropsychopharmacol Biol Psychiatry,2001,25(7):1341-1357.
[12] Liu SJ,Zhang AH,Li HL,et al.Overactivation of glycogen synthase kinase-3 by inhibition of phosphoinositol-3 kinase and protein kinase C leads to hyperphosphorylation of Tau and impairment of spatial memory[J].Neurochem,2003,87(6):1333-1344.
[13] Sandy DW,Joshua DB,Bessie NA,et al. Celastrols as inducers of the heat shock response and cytoprotection[J]. J Biol Chem,2004,279(53):56053-56060.
[14] Ari MC,Ian R.Induction of heat shock proteins in differentiated human and rodent neurons by celastrol[J].Cell Stress Society Internation,2007,12(3):237-244.
[15] Trott A,James DW,Sandy DW,et al.Activation of heat shock and antioxidant responses by the natural product celastrol: transcriptional signaturesof a thiol-targeted molecule[J]. Mol Biol Cell,2008,19(3):1104-1112.

雷公藤红素对肝叶部分切除老年小鼠术后认知功能及海马Tau蛋白磷酸化的影响

Effect of Celastrol on cognitive function and Tau hyperphosphorylation in eldly mice hippocampus after partial hepatectomy

PDF (PC)

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	刘兆丰, 李玲, 那淑芳, 乐江, 叶啟发. 法尼酯X受体翻译后修饰调控机制研究进展[J]. 中国临床药理学与治疗学, 2023, 28(11): 1292-1298.
[2]	杨丽, 柏虎虎, 贺沙沙, 金月, 刘成松. TRPM3的酪氨酸磷酸化参与糖尿病诱发的热痛觉过敏[J]. 中国临床药理学与治疗学, 2022, 27(9): 971-976.
[3]	陈健, 兰宇, 吴勇, 沈伯雄. 肠道菌群紊乱对吸入麻醉患者术后认知功能障碍的影响[J]. 中国临床药理学与治疗学, 2022, 27(6): 639-644.
[4]	厉永亮, 林海燕, 张玲玲, 董伊隆. 地佐辛自控镇痛泵术前应用对老年下肢骨折患者应激反应及认知功能的影响[J]. 中国临床药理学与治疗学, 2022, 27(3): 302-306.
[5]	倪渊博, 张昕, 李仪, 刘存明. 麻醉及镇痛药物与认知功能[J]. 中国临床药理学与治疗学, 2022, 27(12): 1365-1374.
[6]	周敏敏, 余露, 韩超, 顾达民, 雷道赟. 人类胆固醇酯转移蛋白rs5882基因多态性与围术期神经认知功能紊乱的相关性[J]. 中国临床药理学与治疗学, 2021, 26(7): 768-774.
[7]	尹子毅，王峰，赵梦，张铁，王丕琳. 卡培他滨为基础一线方案治疗Her2阴性转移性乳腺癌的单中心回顾性研究及TYMP基因多态性分析[J]. 中国临床药理学与治疗学, 2019, 24(9): 1002-1008.
[8]	俞陈陈，刘树群，刘建龙，曹红，刘雪娇，蔡茜茜. 姜黄素对高血压病大鼠全脑缺血再灌注时海马神经元损伤及皮质酮、SGK1表达的影响[J]. 中国临床药理学与治疗学, 2019, 24(7): 737-743.
[9]	张睿. 右美托咪定改善缺血性脑血管病患者术后认知功能障碍和注意网络功能的临床研究[J]. 中国临床药理学与治疗学, 2019, 24(7): 815-820.
[10]	严洁萍，章水均，张国兵，胡颖，罗丹，江红娟，李敏静. 丁苯酞对S-亚硝基化谷胱甘肽诱导脑微血管内皮细胞损伤的保护作用及机制研究[J]. 中国临床药理学与治疗学, 2019, 24(5): 517-522.
[11]	胡德凤，王轶虎，龙小宇，王广水. 甘麦大枣汤加减方联合认知行为干预对精神分裂症超高危人群的干预作用及对认知功能、生活质量及血清5-HT、MT、TSH水平的影响[J]. 中国临床药理学与治疗学, 2019, 24(5): 546-553.
[12]	官俏兵，韩晨阳，储志远，杨毅，张晓玲. 丁苯酞通过激动cAMP/CREB/BDNF信号通路改善小鼠缺血再灌注后认知障碍的作用机制[J]. 中国临床药理学与治疗学, 2019, 24(2): 152-157.
[13]	陈娟燕，宋水江，徐冬娟，徐琼，李鸿飞. 法舒地尔联合瑞舒伐他汀治疗血管性痴呆对认知功能、C-反应蛋白及氧化应激的影响[J]. 中国临床药理学与治疗学, 2018, 23(10): 1153-1158.
[14]	莫亚莉，夏泳，刘义，陶云海，金曼. 石杉碱甲联合艾司西酞普兰对抑郁症临床疗效及认知功能的影响[J]. 中国临床药理学与治疗学, 2017, 22(9): 1040-1044.
[15]	钟树志，裴东，晁杲，周静，洪宗元. 复元活血汤对大鼠损伤坐骨神经组织p-Src、p-Erk表达的影响[J]. 中国临床药理学与治疗学, 2017, 22(7): 731-737.