Intervention research of estrogen receptor antagonist on cerebral neuroprotective effect of Zuoguiwan Decoction in MCAO rats

Hong LIU; Lili ZHONG; Yuwei ZHANG; Jing YANG; Qiaomei DAI; Ji LI

doi:10.16305/j.1007-1334.2021.2004061

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Intervention research of estrogen receptor antagonist on cerebral neuroprotective effect of Zuoguiwan Decoction in MCAO rats

更新时间：2022-08-03

- Intervention research of estrogen receptor antagonist on cerebral neuroprotective effect of Zuoguiwan Decoction in MCAO rats
- Shanghai Journal of Traditional Chinese Medicine Vol. 55, Issue 11, Pages: 66-73(2021)
- 作者机构：
  
  1.黑龙江中医药大学基础医学院病理教研室（黑龙江　哈尔滨　150040）
  2.黑龙江中医药大学博士后流动站（黑龙江　哈尔滨　150040）
  3.黑龙江中医药大学附属第一医院病理科（黑龙江　哈尔滨　150040）
  4.黑龙江中医药大学基础医学院生理教研室（黑龙江　哈尔滨　150040）
  5.黑龙江中医药大学基础医学院方剂教研室（黑龙江哈尔滨　150040）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2021.2004061
  CLC：
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Hong LIU, Lili ZHONG, Yuwei ZHANG, et al. Intervention research of estrogen receptor antagonist on cerebral neuroprotective effect of Zuoguiwan Decoction in MCAO rats. [J]. Shanghai Journal of Traditional Chinese Medicine 55(11):66-73(2021)
DOI：

Hong LIU, Lili ZHONG, Yuwei ZHANG, et al. Intervention research of estrogen receptor antagonist on cerebral neuroprotective effect of Zuoguiwan Decoction in MCAO rats. [J]. Shanghai Journal of Traditional Chinese Medicine 55(11):66-73(2021) DOI： 10.16305/j.1007-1334.2021.2004061.

摘要

目的,2,观察雌激素受体拮抗剂对左归丸脑神经元保护作用的影响，初步探索中医学“肾脑相关”理论的物质基础。,方法,2,雌性SD大鼠108只，被随机分为6组，分别为假手术组（a组）、单纯脑缺血组（b组）、惊恐伤肾组（c组）、补肾中药组（d组）、雌激素受体拮抗剂组（e组）、脑复康组（f组），每组18只大鼠。除假手术组外，其余各组均用线栓法制备大鼠大脑中动脉阻塞（MCAO）模型。惊恐伤肾组、补肾中药组、雌激素受体拮抗剂组、脑复康组于MCAO手术前10 d进行高台恐吓，补肾中药组、雌激素受体拮抗剂组于MCAO前3 d开始分别给予左归丸汤剂1.62 g/kg灌胃，每日1次，连续给药10 d。脑复康组于MCAO前3 d开始分别给予脑复康悬液0.324 g/kg 灌胃，每日1次，连续给药10 d。雌激素受体拮抗剂组于MCAO手术前3 d同时给予雌激素受体阻断剂ICI182780 5 mg/kg腹腔注射，每日1次，连续给药10 d。采用平横木法检测各组大鼠的运动能力，新奇物认知法及跳台实验检测大鼠的记忆力，HE染色法观察大鼠脑组织形态学变化。,结果,2,与假手术组比较，单纯脑缺血组大鼠运动能力及记忆力均明显下降（,P,<,0.01）；与单纯脑缺血组比较，惊恐伤肾组大鼠运动能力及记忆力明显下降（,P,<,0.05）；与惊恐伤肾组比较，补肾中药组大鼠运动能力及记忆力明显提高（,P,<,0.05）；与补肾中药组比较，雌激素受体拮抗剂组大鼠运动能力及记忆力明显下降（,P,<,0.05）；与补肾中药组比较，脑复康组大鼠运动能力及记忆力无明显差异（,P,>,0.05）。,结论,2,左归丸的脑神经元保护作用可以被雌激素受体拮抗剂阻断，提示左归丸通过雌激素及其受体对脑产生影响，“肾→雌激素及其受体→脑”可能是“肾通于脑”的关键通路之一。

Abstract

Objective,2,To observe the effect of estrogen receptor antagonist on the neuroprotective effect of Zuoguiwan Decoction, and explore the material basis of the theory of "kidney-brain connection" in traditional Chinese medicine.,Methods,2,A total of 108 female SD rats were randomly divided into 6 groups: sham operation group (group a), simple cerebral ischemia group (group b), panic injuring kidney group (group c), Chinese medicine kidney-tonifying group (group d), estrogen receptor antagonist group (group e), Naofukang group (group f), with 18 rats in each group. The middle cerebral artery occlusion (MCAO) model of rats was established by thread occlusion in all groups except sham operation group. Rats in group c, group d, group e and group f were threatened by high platform 10 days before MCAO. Rats in group d and group e were administered with Zuoguiwan Decoction 1.62 g/kg by gavage 3 days before MCAO, once a day for 10 consecutive days. Rats in group f were administered with Naofukang suspension 0.324 g/kg by gavage 3 days before MCAO, once a day for 10 consecutive days. Rats in group e were also administered with the estrogen receptor blocker ICI182780 5 mg/kg intraperitoneally 3 days before MCAO, once a day for 10 consecutive days. The motor ability of rats in each group was measured by a horizontal beam method, the memory of rats was measured by a novel cognition method and platform jumping test, and the morphological changes of brain tissue were observed by HE staining method.,Results,2,Compared with group a, there was a significant decrease of the motor ability and memory of rats in group b (,P,<,0.01); compared with group b, there was a significant decrease of the motor ability and memory of rats in group c (,P,<,0.05); compared with group c, there was a significant improvement of the motor ability and memory of rats in group d (,P,<,0.05); compared with group d, there was a significant decrease of the motor ability and memory of rats in group e (,P,<,0.05); compared with group d, there was no significant difference of the motor ability and memory of rats in group f (,P,>,0.05).,Conclusion,2,The protective effect of Zuoguiwan Decoction on brain can be blocked by estrogen receptor antagonists, suggesting that Zuoguiwan Decoction can affect brain through estrogen and its receptors, and "kidney-estrogen and its receptors-brain" may be one of the key pathways of "kidney communicating with the brain" .

关键词

肾脑相关雌激素左归丸大脑中动脉阻塞雌激素受体拮抗剂模型大鼠中药研究

Keywords

kidney-brain connectionestrogenZuoguiwan DecoctionMCAOestrogen receptor antagonistmodel ratstraditional Chinese herbal medicine research

references

史菘. 灵枢经[M]. 北京：人民卫生出版社，2012.

柴立民. 从益髓生血颗粒调控β-珠蛋白及相关基因表达探讨肾生髓理论的分子机制[D]. 北京：中国中医研究院，2005.

李红梅，张俊龙，陈乃宏. 补肾方对PC12细胞增殖能力及突起形成的影响[J]. 山西中医，2008, 24(6): 42-44.

左占国. 补肾通络畅气法防治脑痴呆[C]//络病学基础与临床研究（3）：中华中医药学会络病分会会议论文集. 北京：中国科技出版社，2007.

冯新玲，杨立娜. 肾脑相关理论的研究进展[J]. 中医药导报，2006, 12(6): 96-98.

刘宏，郝迪，黄树明，等. 补肾方药对中枢神经系统作用的研究进展[J].中医药信息，2014, 31(2): 122-124.

张介宾. 景岳全书集要[M]. 沈阳：辽宁科学技术出版社，2007.

詹青，管强，余敏，等. 左归丸对慢性脑缺血大鼠模型氧化应激损伤的保护作用及其机制[J]. 中华实验外科杂志，2013, 30(9): 1856-1858.

刘宏，刘学伟，张雨薇，等.左归丸对卵巢摘除MCAO模型大鼠BDNF的影响[J]. 黑龙江科技信息，2014, 22(8): 16-17.

刘宏，贾彦，孙世晓，等. 左归丸改善惊恐伤肾脑缺血大鼠记忆力的实验研究[J]. 中国临床药理学杂志，2015, 31(16): 1618-1621.

刘宏，贾彦，仲丽丽，等. 左归丸对惊恐伤肾 MCAO大鼠 BDNF及其受体的影响[J]. 中医药信息，2015, 32(4): 10-14.

刘宏，仲丽丽，张雨薇，等. 左归丸对卵巢摘除MCAO模型大鼠CREB的影响[J]. 上海中医药杂志，2015, 49(12): 67-70.

宋亚琼，赵平. 雌激素与神经保护的研究进展[J]. 国际眼科杂志，2010,10(3): 523-536.

吴乐，陈文军. 雌激素的神经保护作用及其机理[J]. 神经解剖学杂志，2005, 21(1): 95-97.

刘娅迪，陆瑞婷，王迪芬. 雌激素对脑缺血再灌注损伤自由基代谢及神经保护作用研究[J]. 创伤与急危重病医学，2019, 7(5): 295-297.

LONGA E Z, WEINSTEIN P R, CARLSON S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1): 84-91.

LEE J Y, CHOI S Y, OH T H, et al. 17β-Estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting RhoA-JNK3 activation after spinal cord injury[J]. Endocrinology, 2012, 153(8): 3815-3827.

刘宏，仲丽丽，张雨薇，等. 基于左归丸治疗脑缺血再灌注损伤的肾通于脑理论生物学实质探讨[J]. 时珍国医国药，2020, 31(10): 2316-2321.

FEENEY D M, GONZALEZ A, LAW W A. Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury[J]. Science, 1982, 217(4562): 855-857.

TANG Y P, SHIMIZU E, DUBE G R, et al. Genetic enhancement of learning and memory in mice[J]. Nature, 1999, 401(6748): 63-69

张慧敏，朱文烽，庞晓平，等. 不同剂量多奈哌齐对APP/PS1-AD 转基因小鼠学习记忆功能的改善作用[J]. 浙江医学，2019, 41(12): 1286-1289.

陈奕安. 六味地黄汤对先天不足鼠脑发育的影响[D]. 长沙：湖南中医药大学，2011.

李红梅，张庞龙，陈乃宏，等. 补肾方对PC12细胞增殖能力及突起形成的影响[J]. 山西中医，2008, 24(6): 42-44.

唐璐，孙塑伦，高颖，等. 地黄饮子加减方对MCAO模型大鼠HPA轴影响的实验研究[J]. 中国中医基础医学杂志，2011, 17(3): 273-275.

常静玲，刘剑，高颖. 论中风后失语从肾论治的理论渊源及现代生物学基础研究[J]. 中华中医药杂志，2012, 27(7): 1904-1907.

王米渠. 试论“肾通于脑”的信息神经观[J]. 长春中医学院学报，1997, 13(6): 1-2.

冯晓芬. 滋补肾精方对雌性小鼠生殖内分泌及免疫功能调节作用的实验研究[D]. 兰州：兰州大学，2010.

李莉，孙竹春. 左归丸治疗更年期综合征72例[J]. 上海中医药杂志，2001, 35(3): 26-27.

林源泉. 左归丸加味治疗肾阴虚型更年期综合征的临床研究[D]. 广州：广州中医药大学，2007.

叶晓平，段恒. 左归丸对大鼠生殖器官发育与雌激素水平影响的实验研究[J]. 河南中医，2014, 34(6): 1050-1051.

李红梅，苗竹林，王奇玲，等. 左归丸对免疫性卵巢早衰小鼠性激素的影响[J]. 中国现代应用药学，2010, 27 (13): 1161-1164.

黄焕. 绝经女性性激素与脑梗死关系研究[J]. 现代实用医学，2009, 21(7): 758-758.

张雪花，周德生. 性激素与脑梗死相关性研究进展[J]. 中医药导报，2006, 12(3): 72-74.

彭钢，李耀华. 雌激素对雌性大鼠缺血性卒中的神经保护作用[J]. 齐齐哈尔医学院学报，2003, 24(9): 961-965.

孟祥君，张茂林，杨志甫. 雌激素及其受体的脑保护作用[J]. 北方药学，2011, 8(1): 52-54.

徐杰，邵正仁，戴忠辉，等. 雌二醇对缺血性脑损伤的保护作用[J]. 解剖学研究，2000, 22(1): 35-36.

杨丽娟. 雌激素对脑缺血再灌注损伤神经元的保护作用及机制探讨[D]. 长沙：中南大学，2012.

AGUIRRE C C, BAUDRY M. Progesterone reverses 17 beta-estradiol-mediated neuroprotection and BDNF induction in cultured hippocampal slices[J]. Eur J Neurosci, 2009, 29(3): 447-454.

朱加应，张广云，王建怡，等. 雌激素及雌激素受体α 减轻谷氨酸对神经细胞的损伤[J].中国病理生理杂志，2013, 30(1): 121-127.

KUNZLER J, YOUMANS K L, YU C, et al. APOE modulates the effect of estrogen therapy on Aβ accumulation EFAD-Tg mice[J]. Neurosci Lett, 2014(560): 131-136.

KITAMURA N, ARAYA R, KUDOH M, et al. Beneficial effects of estrogen in a mouse model of cerebrovascular insufficiency[J]. PLoS One, 2009, 4(4): e5159.

BEYER C. Estrogen and the developing mammalian brain[J]. Anat Embryol (Berl), 1999, 199(5): 379-390.

SHAO B, CHENG Y, JIN K. Estrogen, neuroprotection and neurogenesis after ischemic stroke[J]. Curr Drug Targets, 2012, 13(2): 188-198.

LI R, SHEN Y. Estrogen and brain: synthesis, function and diseases[J]. Front Biosci, 2005 (10): 257-267.

KOERNER I P, ZHANG W, CHENG J, et al. Soluble epoxide hydrolase: regulation by estrogen and role in the inflammatory response to cerebral ischemia[J]. Front Biosci, 2008 (13): 2833-2841.

STRÓZYŃSKA E, FISZER U. Relationship between stroke and hormonal changes in various periods of life time[J]. Neurol Neurochir Pol, 2003, 37(4): 889-901.

刘爽. 引火汤含药血清对Aβ25-35诱导PC12 细胞损伤的抑制作用[D]. 哈尔滨：黑龙江中医药大学，2013.

DONOVAN N J, KENDALL D L, HEATON S C, et al. Conceptualizing functional cognition in stroke[J]. Neurorehabil Neural Repair, 2008, 22(2): 122-135.

LIN R, LIN Y, TAO J, et al. Electroacupuncture ameliorates learning and memory in rats with cerebral ischemia-reperfusion injury by inhibiting oxidative stress and promoting p-CREB expression in the hippocampus[J]. Mol Med Rep, 2015, 12(5): 6807-6814.

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