Name: behavioral and network pharmacology-based analyses for the traditional mongolian medicine zadi-5 in a rat model of depression
Uploaded: 2023-02-24T13:25:00
Description: Watch this Scientific Journal Video about Behavioral and Network Pharmacology-Based Analyses for the Traditional Mongolian Medicine Zadi-5 in a Rat Model of Depression at JoVE.com

我们感谢中国内蒙古医科大学蒙古医学院提供的仪器和实验室。本研究得到了国家自然科学基金（81760762）和内蒙古卫生健康委员会科技计划项目（202201300）的支持。

所有实验方案均经内蒙古医科大学动物实验伦理护理委员会批准，并遵循美国国立卫生研究院动物护理伦理指南。将8周龄（200g±20g）的雄性Sprague Dawley（SD）大鼠饲养在受控温度（22°C±2°C）和湿度（55%±15%）的房间中，在12小时/12小时调节的光/暗循环下，持续1周。网络药理学分析的工作流程见 图1 。
1.大鼠行为测试
<ol><li>建立CUMS大鼠模型...

<ol>
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抑郁症是一种以情绪低落、快感缺乏和精力不足为特征的精神疾病。这种疾病伴有分心、认知功能障碍、社交退缩、失眠、性功能障碍和胃肠道疾病18,19。在抑郁症的研究中，建立动物模型对于理解新药的病理机制和作用至关重要。在这项研究中，通过协议第 2 节和表 1 中描述的刺激建立了 CUMS 诱导的大鼠抑郁模型，以模拟来自社会、家庭?...

抑郁症，也称为重度抑郁症 （MDD），是一种严重的神经精神疾病，导致社会医疗和经济负担日益加重。由于相关的复杂性、发病率和死亡率，已经进行了大量研究以寻找该疾病的补救措施 1,2。根据世界卫生组织的一项心理健康调查，目前全球约有 3.5 亿人患有抑郁症及其相关症状。据预测，到 2030 年，抑郁症将超过癌症和心血管疾病，成为全球疾病负担的主要原因。因此，在不久的将来，抑郁症的预防和治疗将成为全球优先事项3.MDD的发病机制尚未阐明。尽管如此，它通常归因于以下因素：遗传易感性、下丘脑-垂体-肾上腺轴功能障碍、神经递质分泌减少、神经免疫失调诱导的神经炎症、细胞凋亡和细胞增殖减少 4,5。
在这些因素中，神经免疫失调诱导的神经炎症和神经营养因子分泌改变因其在抑郁症和许多其他精神疾病发展中的作用而受到特别关注6。在过去的十年中，学者们已经证明海马体是再生神经功能的主要场所，并参与调节情绪和认知。在这方面，海马神经元被认为是正在开发的抗抑郁药物的新治疗靶点 7,8。此外，据报道，海马体还参与学习和巩固记忆的短期和长期记忆。具体来说，海马CA1区域锥体神经元的缺乏会导致逆行和顺行性遗忘症9。典型的抗抑郁治疗策略旨在增强海马齿状回的细胞增殖和神经发生。基于药物化学技术合成的天然产物衍生化合物和小分子被认为是治疗各种神经精神疾病的创新治疗剂的主要来源。
蒙古族传统药物历史悠久，理论医学体系得到充分支持，是蒙古高原游牧民族的后裔，由于各种药用成分协同作用，产生协同作用，这些药物表现出多靶点和多通路效应。Zadi-5 是此类药物中公认的配方，最早记录在“高石博士的临床经验”中，由一位杰出的蒙古临床医生高石博士（1804-1876 年）撰写。在蒙古，使用这些药丸治疗痛苦、心悸、刺激和心脏刺痛的症状已经是很长一段时间的临床实践10,11。此外，Zadi-5 已被证明可缓解受影响患者的中风后抑郁症12。最近对 CUMS 的实验研究表明，Zadi-5 制剂通过调节中枢神经递质13 来缓解抑郁症;事实上，在 Zadi-5 中，已经检测到脑源性神经营养因子 （BDNF） 和酪氨酸激酶受体 B （TrkB） 水平升高，并与抑郁症大鼠模型中的学习和记忆改善相关14。然而，Zadi-5缓解抑郁症的确切作用机制尚未阐明。
本研究旨在通过行为测试证明Zadi-5对大鼠抑郁症的治疗效果，并使用中医药系统药理学（TCMSP）和瑞士靶点预测法鉴定Zadi-5的成分，以预测蒙古传统药物Zadi-5治疗抑郁症的潜在机制。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Cytoscape software</td>
			<td></td>
			<td>&#160;version 3.7.0</td>
			<td></td>
		</tr>
		<tr>
			<td>Fluoxetine</td>
			<td>Lilly Suzhou Pharmaceutical Co., Ltd</td>
			<td>J20160029</td>
			<td></td>
		</tr>
		<tr>
			<td>Morris water maze video trail analysing system&#160;</td>
			<td>Tai Meng Tech Co., Ltd</td>
			<td>WMT-200</td>
			<td></td>
		</tr>
		<tr>
			<td>Sprague Dawley rats</td>
			<td>Beijing Biotechnology Co., Ltd, China</td>
			<td>&#160;SCXK (JING) 2016-0002</td>
			<td></td>
		</tr>
		<tr>
			<td>&#160;video tracking system</td>
			<td>Tai Meng Tech Co., Ltd</td>
			<td>ZH-ZFT</td>
			<td></td>
		</tr>
		<tr>
			<td>Zadi-5 pill</td>
			<td>Pharmaceutical Preparation Center of International Mongolian Hospital, Inner Mongolia, China</td>
			<td>M1301006</td>
			<td></td>
		</tr>
	</tbody>
</table>

behavioral and network pharmacology-based analyses for the traditional mongolian medicine zadi-5 in a rat model of depression

Zadi-5是一种传统的蒙古药物，广泛用于治疗抑郁症和刺激症状。尽管Zadi-5对抑郁症的治疗作用已在先前报道的临床研究中得到证实，但药物中存在的活性药物化合物的身份和影响尚未完全阐明。本研究使用网络药理学来预测药物成分并鉴定Zadi-5药丸中的治疗活性化合物。在这里，我们建立了慢性不可预测的轻度应激（CUMS）大鼠模型，并进行了开放场试验（OFT）、莫里斯水迷宫（MWM）分析和蔗糖消耗试验（SCT），以研究Zadi-5在抑郁症中的潜在治疗效果。本研究旨在证明 Zadi-5 对抑郁症的治疗效果，并预测 Zadi-5 对抗该疾病的关键途径。氟西汀组（阳性对照）和Zadi-5组的纵横评分（OFT ）、SCT和跨区数显著高于未处理的CUMS组大鼠（P < 0.05）。根据网络药理学分析结果，发现PI3K-AKT通路对Zadi-5的抗抑郁作用至关重要。

动物行为测试 CUMS诱导的大鼠抑郁模型中的行为测试结果 在CUMS刺激前，测试组之间的OFT评分、蔗糖消耗量和MWM分析没有显著差异。建立CUMS模型后，MOD组的纵向和水平得分均低于CON组（P < 0.05）。与MOD组相比，POS组和Zadi-5组的纵向和水平得分显著更高（P < 0.05）（图2A，B）。
第0天，试验组的蔗糖消耗量（%...

Watch this Scientific Journal Video about Behavioral and Network Pharmacology-Based Analyses for the Traditional Mongolian Medicine Zadi-5 in a Rat Model of Depression at JoVE.com

Behavioral and Network Pharmacology-Based Analyses for the Traditional Mongolian Medicine Zadi-5 in a Rat Model of Depression

本方案描述了一种对蒙古传统药物Zadi-5在抑郁症中的治疗效果的行为测试验证和生物信息学预测的方法。

基于行为和网络药理学的蒙古医学Zadi-5在抑郁症大鼠模型中的分析

Zadi-5 is a traditional Mongolian medicine that is widely used for the treatment of depression and symptoms of irritation. Although the therapeutic ...

Zadi-5 治疗抑郁症的疗效可以通过行为测试确定，而网络药理学可以预测其效力背后的潜在机制。网络药理学可以支持对具有复杂作用机制的传统药物的探索，并进一步减少研究所需的时间和费用。在神经系统疾病动物模型中，露天试验、蔗糖消耗试验和莫里斯水迷宫等测试是评估食欲、动机水平、学习能力和记忆力的黄金标准。这些测试是简单、客观、合理的评估方法。建立动物模型对于理解抑郁症研究中新药的病理机制和作用至关重要。为了建立一个良好的抑郁模型，研究人员必须对刺激强度进行适当的排序和调整。首先，将选定的抑郁刺激与隔离相结合，对除对照组以外的所有大鼠施加28天，并将大鼠饲养在单独的笼子中。要执行开放场测试，请将黑匣子划分为九个面积相等的方形区域。为盒子配备视频跟踪分析系统。最后一次管饲后一天，将老鼠放在中心广场上，记录其水平和垂直活动三分钟。然后，将所有停顿时交叉的方格数作为水平活动进行评分，并将站立和梳理作为垂直活动进行评分。每次测试后，用75%的酒精清洁盒子，以去除大鼠的气味，以便进行后续测试。接下来，通过在食用前后称量各自的瓶子来执行蔗糖消耗测试。并使用此公式计算第 0 天、第 7 天、第 14 天、第 21 天和第 28 天的 60 分钟蔗糖偏好率。要执行莫里斯水迷宫测试，请将游泳池分为四个象限。将象限从一到四排序，并将隐藏平台放置在水面以下一厘米的第三象限中。将牛奶添加到池中以获得一定程度的不透明度。然后将大鼠受试者放入不同象限的迷宫中，寻找平台120秒。并使用 Morris Water Maze 视频轨迹分析系统记录延迟时间。将大鼠受试者置于池中的固定位置。如果受试者在 120 秒内找不到隐藏平台，则将延迟记录为 120 秒。接下来，移开平台，将老鼠放入水中，并记录 120 秒的区域穿越次数。浏览中医药体系的药理学网页，在药材名称部分输入肉豆蔻科精液种子、al-glandia-radiks 根和 piperis longi fructus，以获取化学品的名称。将口服生物利用度（OB）的药代动力学指数设置为大于30%，将类药指数设置为大于0.18。在中药药典中搜索活性成分，找出每种成分的化学名称。接下来，在 Pub Chem 中搜索已识别的化学名称，以找到异构体微笑或墨色。使用 SEA、Batman 和 Swiss 靶标预测，用异构微笑或墨色来识别活性成分的靶蛋白，并找到重叠的蛋白。将数据复制到 Excel 文件。接下来，使用 GeneCards、DisGeNET 和 DrugBank 中的关键字 depression and depressive disorder 搜索并确定抑郁症的潜在蛋白质靶点。将数据复制到 Excel 文件。浏览维恩图并上传列表一中的抑郁症目标。然后上传列表二中 Zadi-5 活动组件的目标并提交。获取维恩图并过滤掉重叠的目标候选者。构建一个名为 network 的电子表格。还要构造一个称为 type 的电子表格。将片材导出到Cytoscape构建网络，Zadi-5草药成分疾病靶点。在字符串数据库中设置公共目标以分析它们的交互作用。将蛋白质类型设置为智人。将交互阈值设置为 0.9 以仅选择经过实验验证的类型，并且不显示孤岛节点。打开DAVID工具，将Zadi-5的86个潜在抗抑郁靶点粘贴到起始分析支架中，研究相关的信号通路。下载小桶通路文档。从富集分析中选择PI3k-AKT通路中的基因，并将它们粘贴到电子表格上以构建类型和网络文档。将网络文档类型导出到 Cytoscape 以生成 PI3K-AKT 可视化化合物靶标通路网络。测试动物组在慢性不可预测的轻度应激或CUMS刺激之前没有显着差异。建立CUMS模型后，该组的纵向和水平得分均低于对照组。与模型组相比，阳性对照组和Zadi-5组的纵向和水平得分显著更高。在第0天，测试组在蔗糖消耗量方面没有显着差异。第28天，Zadi-5和阳性对照组高于模型组。在莫里斯水迷宫中，与对照组相比，模型组找到平台的延迟明显更高。阳性对照组和Zadi-5组的潜伏期低于模型组。关于区域交叉计数，模型组显示的交叉次数少于对照组。阳性对照组和 Zadi-5 组比模型组表现出更多的交叉。维恩图分析显示，在1000个抑郁症相关蛋白靶点中，有86个重叠靶点是Zadi-5的关键抑郁症相关靶点。基于这些发现，构建了Zadi-5草本成分疾病靶点，并构建了靶点候选物的蛋白-蛋白相互作用网络分析。根据KEG通路分析，PI3K-AKT信号通路排名第七。它与许多信号通路有关。因此，PI3K-AKT通路被认为比其他富集通路更重要。在尝试此过程时，避免连续几天重复相同类型的刺激至关重要。在在线数据库中对Zadi-5的成分进行分析后，液相色谱、质谱和核磁共振波谱可以保证验证质量。

Research

JoVE Journal

Medicine

Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD

在动物模型揭示神经，血液，创伤后应激障碍和行为相关因素的生物标志物

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for ...

科研

医学

Reduced Complications after Arterial Reconnection in a Rat Model of Orthotopic Liver Transplantation

矫形肝移植大鼠模型中动脉重联后并发症减少

The rat orthotopic liver transplantation (OLT) model is a powerful tool to study acute and chronic rejection. However, it is not a complete representation ...

Acupuncture in a Rat Model of Asthma

哮喘鼠模型中的针灸

A high platform can fix rats without restriction and completely expose the acupoints on the back during acupuncture manipulation. This article describes ...

Establishment of a Simple and Effective Rat Model for Intraoperative Parathyroid Gland Imaging

建立简单有效的术中甲状旁腺成像大鼠模型

Parathyroid gland (PG) identification is a critical unmet need in thyroidectomy. The identification of the PG is challenging in thyroid surgery as it is ...

A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes

一种构建1型糖尿病大鼠伤口模型的方案

A single high dose of streptozotocin injection followed by full-thickness skin excision on the dorsum of rats is a common method for constructing animal ...

Network Pharmacology Prediction and Metabolomics Validation of the Mechanism of Fructus Phyllanthi against Hyperlipidemia

网络药理学预测及代谢组学验证 凤仙花抗高脂血症的机制

Hyperlipidemia has become a leading risk factor for cardiovascular diseases and liver injury worldwide. Fructus Phyllanthi (FP) is an effective drug ...

A Traditional Chinese Medicine Characteristic Therapy for Bronchial Asthma: Moxibustion

支气管哮喘的中医特色疗法：艾灸

Bronchial asthma is a chronic inflammatory disease of the airway which can lead to symptoms such as recurrent wheezing, shortness of breath, chest ...

Comparative Study of Blood Collection Techniques in Rats

Modified Tail Vein and Penile Vein Puncture for Blood Sampling in the Rat Model

Context Dependent Blood Collection Methods in Rats (Video) | JoVE

改良尾静脉和静脉穿刺用于大鼠模型中的血液采样

Blood samples are required in most experimental animal designs to assess various hematological parameters. This paper presents two procedures for blood ...

Standardized Tuina Protocol for Rat DRG Compression Model

Analgesic Effect of Tuina on Rat Models with Compression of the Dorsal Root Ganglion Pain

Analgesic Effect of Tuina on Rat Models with Compression of the Dorsal Root Ganglion Pain (Video) | JoVE 

推拿对大鼠模型的镇痛作用，压迫背根神经节疼痛

Neuropathic pain is a prevalent condition that affects 6.9%-10% of the population and results from nerve damage due to various etiologies, such as lumbar ...

Tuina Therapy for Frozen Shoulders in a Rat Model

Tuina in a Frozen Shoulder Rat Model: An Efficient and Reproducible Protocol

Investigating the Effectiveness of Tuina Therapy for Frozen Shoulder (Video) | JoVE

冻肩大鼠模型中的推拿：一种高效且可重复的方案

Frozen shoulder (FS) is a common condition with no defined optimal therapy. Tuina therapy, a traditional Chinese medicine (TCM) technique used to treat FS ...