WO2024168474A1 - 根据p值比较不同药物对抗焦虑效果的分析方法和装置 - Google Patents

根据p值比较不同药物对抗焦虑效果的分析方法和装置 Download PDF

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WO2024168474A1
WO2024168474A1 PCT/CN2023/075706 CN2023075706W WO2024168474A1 WO 2024168474 A1 WO2024168474 A1 WO 2024168474A1 CN 2023075706 W CN2023075706 W CN 2023075706W WO 2024168474 A1 WO2024168474 A1 WO 2024168474A1
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drug
test
group
control group
different drugs
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景晓源
刘欣安
王立平
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Shenzhen Institute of Advanced Technology of CAS
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Shenzhen Institute of Advanced Technology of CAS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo

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  • the present invention relates to the field of bioinformatics, and in particular to an analysis method and device for comparing the antianxiety effects of different drugs according to P values.
  • the existing evaluation of the anti-anxiety effects of different drugs is mostly used in clinical research.
  • the research subjects are patients with anxiety and depression.
  • the effects of patients after taking the drugs are evaluated through questionnaires. Most of them are comparisons before and after the use of a drug or comparisons of the efficacy between two drugs.
  • the present invention provides an analysis method and device for comparing the antianxiety effects of different drugs according to P values.
  • the first aspect of the present invention provides an analytical method for comparing the anti-anxiety effects of different drugs based on P values, the method comprising: S1, determining a stress model; S2, dividing the test samples into a control group and a drug group, and performing at least two behavioral tests after the control group and the drug group are subjected to the stress model, to obtain the test results of the control group and the test results of the drug group; wherein, the test samples in the control group are not administered, and the test samples in the drug group are administered; the types of the drugs to be tested are at least three, and the number of drug groups is at least three; each of the behavioral tests includes at least one behavioral parameter; S3, performing a one-way analysis of variance on the test results of the drug group and the test results of the control group, to obtain the P value of each drug group in each behavioral parameter; S4, marking the P value of each drug group in each behavioral parameter with the same proportion of * numbers for probability degree; S5, counting the total number of * numbers obtained for each drug to be tested, and ranking the drugs to
  • the stress model includes suspending the tails of the test samples in the control group and the drug group for 30 minutes, applying electric shock to the soles of the feet at 0.5 mA ⁇ 2 seconds, for a total of 10 cycles, with an interval of 10 seconds and restraint for 1 hour in each cycle, for four consecutive days;
  • the behavioral tests include open field test, elevated plus maze test, black and white box test, and tail suspension test.
  • test results of the control group and the drug group include the middle zone time, the number of middle entries and the total moving distance in the open field test, the open arm time and the total immobility time in the elevated plus maze test, the white box time, the number of white box/black box crossings, the latency time in the black-white box test and the immobility time in the tail suspension test.
  • the number of the drug groups is consistent with the number of types of the drugs to be tested.
  • the pressure stress model before determining the pressure stress model, it also includes: gavage the test samples of the control group and the drug group for four consecutive weeks; wherein the test samples of the control group are gavaged with physiological saline, and the test samples of the drug group are gavaged with the drug to be tested.
  • a second aspect of the present invention provides an electronic device, comprising: at least one processor; and a memory communicatively connected to the at least one processor; wherein the memory stores instructions executable by the at least one processor, and the instructions are executed by the at least one processor so that the at least one processor can execute the above-mentioned analysis method for comparing the anti-anxiety effects of different drugs based on P values.
  • a third aspect of the present invention provides a computer-readable storage medium storing a computer program, which, when executed by a processor, implements the above-mentioned analysis method for comparing the anti-anxiety effects of different drugs based on P values.
  • the technical solution provided by the present invention has at least the following advantages:
  • the present invention provides an analysis method and device for comparing the antianxiety effects of different drugs according to P values, mainly for evaluating the antianxiety effects of mice as the research object, and provides a method for comprehensively analyzing the antianxiety effects for research that requires multiple behavioral tests.
  • the method can comprehensively analyze the antianxiety effects of three or more drugs, and provide a basis for developing and determining which drug to use.
  • FIG1 shows the results of behavioral tests of the tested drugs 2-FL, Cerebiome+R215 and 2-FL+Cerebiome+R215 in an embodiment of the present invention
  • FIG2 is a summary diagram of behavioral test results for the test drugs 2-FL, Cerebiome+R215 and 2-FL+Cerebiome+R215 according to the P value marked with * in an embodiment of the present invention
  • FIG. 3 is a schematic diagram of the structure of an electronic device provided by the present invention.
  • mice cannot express emotions directly like humans, we can only use a variety of behavioral tests to reflect the emotions of mice.
  • the existing research through one-way analysis of variance only the comparison of the anti-anxiety effects of the two drugs in a specific behavioral parameter was obtained. In this case, there may be differences in the expression of the effects of the drugs in different behaviors, and there is no comprehensive analysis of the effects of different drugs.
  • the present invention aims to comprehensively evaluate the anti-anxiety effects of three or more drugs, obtain a specific drug efficacy ranking, and provide a reference for those in need.
  • the first aspect of the present invention provides an analytical method for comparing the anti-anxiety effects of different drugs based on P values, the method comprising: S1, determining a stress model; S2, dividing the test samples into a control group and a drug group, and performing at least two behavioral tests after the control group and the drug group are subjected to the stress model, to obtain the test results of the control group and the test results of the drug group; wherein, the test samples in the control group are not given medication, and the test samples in the drug group are given medication; the types of the drugs to be tested are at least three, and the number of drug groups is at least three; each of the behavioral tests includes at least one behavioral parameter; S3, performing a one-way analysis of variance on the test results of the drug group and the test results of the control group, to obtain the P value of each drug group in each behavioral parameter; S4, marking the P value of each drug group in each behavioral parameter with the same proportion of * numbers for probability degree; S5, counting the total number of * numbers obtained for each drug to be tested, and ranking the
  • oral gavage and “oral administration” mean that before administration, the experimental animals are generally fasted for 12 to 16 hours, after which the animals are fixed and the drug solution is injected directly into the animal's stomach through the animal's mouth using a syringe and an oral gavage needle.
  • the term "open field test” is also called an open box test. It is a method for evaluating the autonomous behavior, exploratory behavior and tension of experimental animals in a new and strange environment. The frequency and duration of certain behaviors of experimental animals in a new and strange environment reflect the autonomous behavior and exploratory behavior of experimental animals in unfamiliar environments.
  • the open field test observes and studies the neuropsychiatric changes of experimental animals and various behaviors after entering an open environment. For example, animals are afraid of new open environments and mainly move in the peripheral areas, and are less active in the central area, but the exploratory characteristics of animals prompt them to move in the central area. The motivation for domain activities can also be observed, and the anxiety caused by it can also be observed. Central nervous system stimulants can significantly increase autonomous activities and reduce exploratory behaviors. A certain dose of antipsychotic drugs can reduce exploratory behaviors without affecting autonomous activities.
  • the terms "elevated plus maze test” and “elevated plus maze” refer to the use of animals' exploratory characteristics of novel environments and their fear of high-hanging open arms to form conflicting behaviors to examine the anxiety state of animals.
  • the elevated plus maze has a pair of open arms and a pair of closed arms. Rodents tend to move in the closed arms due to their dark preference, but they will move in the open arms out of curiosity and exploratory nature.
  • animals simultaneously have the urge to explore and fear, which creates conflicting behaviors of exploration and avoidance, thereby generating anxiety.
  • Anti-anxiety drugs can significantly increase the number and time of entering the open arms.
  • the elevated plus maze is widely used in scientific research and computer-assisted teaching in multiple disciplines such as new drug development/screening/evaluation, pharmacology, toxicology, preventive medicine, neurobiology, animal psychology and behavioral biology. It is a classic experiment for conducting behavioral research, especially anxiety and depression research.
  • black and white box experiment or "light and dark box” refers to a light and dark box in which mice or rats prefer to move in the dark box (black box), but the animal's exploratory habits prompt it to try to explore the light box (white box). However, the bright light stimulation of the light box inhibits the animal's exploratory activities in the light box. Anti-anxiety can remove this inhibitory effect.
  • tail suspension test is a classic method that can quickly evaluate the efficacy of antidepressants, stimulants, and sedatives.
  • the principle is to use the fact that mice attempt to escape after being suspended by their tails but cannot escape, so they give up struggling and enter a unique state of depression and immobility. During the experiment, the immobility time of the animals is recorded to reflect the depressive state. Antidepressants and stimulants can significantly shorten and change their state.
  • the model animal used in the present invention is mouse, and mice with abnormal indicators during the test are eliminated (i.e., those marked as abnormal values in FIG. 1 ) to enhance the integrity of the experiment.
  • test drugs 2-FL, Cerebiome+R215 and 2-FL+Cerebiome+R215 were tested by open field test, elevated plus maze test, black-white box test and tail suspension test. The test results are shown in Figures 1 and 2.
  • Open field experiment After the four-day stress modeling, the mice were placed in the open field laboratory at 8:00 a.m. one day to adapt for 1 hour. The experimental environment was kept quiet, and the temperature and humidity were the same as those in the mouse breeding room. The mice were then placed in the center of the bottom of a 35cm ⁇ 35cm ⁇ 30cm transparent box, and video and timing were performed at the same time. The video equipment was set up 2m above the reaction box, and its field of view could cover the entire open field. The total distance the mice moved in the open field and the time they stayed in the central area were recorded using visuTrack software, and video and recording were stopped after 10 minutes of observation. The mice were taken out and the inner wall and bottom of the reaction box were cleaned, and 75% alcohol was sprayed to remove the odor so that they could be used again in the next experiment.
  • Elevated plus maze test Before the experiment, the mice were placed in the open field to adapt for 15 minutes, and then the mice to be tested were gently placed in the center of the cross, and video and recording were performed at the same time. Each mouse was observed for about 7 minutes, and the visuTrack software was used to record the mice's movements in the open arms. After the experiment, the mice were taken out and the open and closed arms were cleaned with 75% alcohol so that they could be used in the next experiment.
  • Black and white box experiment The black and white box (45cm ⁇ 27cm ⁇ 27cm) has a dark box occupying half, with a cover on the top; the light box occupies half, with bright light illumination, and there is a 7.5cm ⁇ 7.5cm doorway in the partition wall between the two boxes for animals to pass through.
  • the light and dark boxes are placed on the Animex activity counter, which can simultaneously record the animal's motor activity. The animal is placed in the center of the light box for a certain period of time after drug administration, and the number of box crossings within 5 minutes, the residence time in the light box, and the latency period of entering the dark box from the light box for the first time are recorded.
  • Tail suspension test Use a special tail suspension tester to fix the tail of the animal so that its head hangs downward, and record a series of parameters during the process of the animal in this environment producing a desperate immobile state.
  • Method 1 Fix the back 1/3 of the mouse's tail with tape, hang it on a bracket, and keep the head 15 cm away from the table. Take a video. The video background is in sharp contrast with the mouse's fur color. White mice use a black background. Stop the timing after 6 minutes, and use the small animal behavior analysis software: visuTrack software to count the immobility time of the mouse in the last five minutes (1 to 6 minutes).
  • the drug administered to drug group A was 2-FL
  • the drug administered to drug group B was Cerebiome+R215
  • the drug administered to drug group C was 2-FL+Cerebiome+R215.
  • Figure 1 the results of the open field, elevated plus maze, black-and-white box, and tail suspension tests were analyzed by one-way ANOVA and Tukey multiple comparisons using Graphpadprism8 software.
  • the 2-FL+Stress group and the 2-FL+Cerebiome+R215+Stress group significantly increased the time in the middle zone and the number of entries to the middle zone compared with the VEH+Stress group
  • the Cerebiome+R215+Stress group significantly increased the time in the middle zone compared with the VEH+Stress group.
  • the 2-FL+Stress group and the Cerebiome+R215+Stress group significantly increased the time in the white box compared with the VEH+Stress group.
  • the 2-FL+Stress group, Cerebiome+R215+Stress group, and 2-FL+Cerebiome+R215+Stress group significantly reduced the immobility time compared with the VEH+Stress group.
  • the middle zone time of Cerebiome+R215 group (i.e. drug B group) in the open field test was counted as *, and in the black and white box test The time in the white box was counted as *, the time spent still in the tail suspension test was counted as ***, and the total * was 5.
  • the time in the middle zone of the drug 2-FL+Cerebiome+R215 group (i.e., drug group C) in the open field test was counted as **, the number of middle entries was counted as *, and the immobility time in the tail suspension test was counted as ***, with a total of 6.
  • the present invention has been tested, simulated and used to prove the effectiveness of the analysis method.
  • the results show that the present invention can comprehensively analyze and rank the efficacy of different drugs.
  • another embodiment of the present invention provides an electronic device, including: at least one processor 110; and a memory 111 communicatively connected to the at least one processor; wherein the memory 111 stores instructions executable by the at least one processor 110, and the instructions are executed by the at least one processor 110 so that the at least one processor 110 can execute any of the above method embodiments.
  • the memory 111 and the processor 110 are connected in a bus manner, and the bus may include any number of interconnected buses and bridges, and the bus connects various circuits of one or more processors 110 and the memory 111 together.
  • the bus can also connect various other circuits such as peripheral devices, voltage regulators, and power management circuits, which are all well known in the art, so they are not further described in this article.
  • the bus interface provides an interface between the bus and the transceiver.
  • the transceiver can be one element or multiple elements, such as multiple receivers and transmitters, providing a unit for communicating with various other devices on a transmission medium.
  • the data processed by the processor 110 is transmitted on a wireless medium through an antenna, and further, the antenna also receives data and transmits the data to the processor 110.
  • the processor 110 is responsible for managing the bus and general processing, and may also provide various functions, including timing, peripheral interfaces, voltage regulation, power management, and other control functions.
  • the memory 111 may be used to store data used by the processor 110 when performing operations.
  • Another embodiment of the present invention relates to a computer-readable storage medium storing a computer program, which implements the above method embodiment when executed by a processor.
  • the aforementioned storage medium includes: U disk, mobile hard disk, read-only memory (ROM, Read-Only Memory), random access memory (RAM, Random Access Memory), disk or optical disk and other media that can store program codes.

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Abstract

一种根据P值比较不同药物对抗焦虑效果的分析方法和装置，该方法包括：S1、确定压力应激模型；S2、将测试样本分为对照组和药物组，在接受压力应激后进行至少两种行为测试，得到对照组测试结果和药物组测试结果；其中，药物组的组数为至少三组；每个测试方法包括至少一个行为参数；S3、将药物组的测试结果与对照组测试结果进行单因素方差分析，获得每组药物组在每个行为参数中的P值；S4、对每组药物组在每个行为参数中的P值，以同比例的*号个数进行概率程度标记；S5、统计每种待测药物获得的*号总数，并对待测药物进行抗焦虑效果排序。

Description

根据P值比较不同药物对抗焦虑效果的分析方法和装置 技术领域
本发明涉及生物信息技术领域，具体涉及一种根据P值比较不同药物对抗焦虑效果的分析方法和装置。
背景技术
现有对不同药物抗焦虑效果的评价多用于临床研究，研究对象为焦虑抑郁症患者，通过问卷调查的方式评估患者在服用药物后的效果，多为一种药物使用前后比较或两种药物之间药效的比较。对于研究对象是小鼠的实验，通常为一个是主要探究药物，另一个作为阳性对照存在，在使用单因素方差后，两两比较药物间是否存在显著差异。
但现有的研究通过单因素方差分析后，只得到了在某个具体的行为参数中，两种药物抗焦虑效果的比较，这种情况就可能存在不同行为中药物的效果表达存在差异，没有综合的分析不同药物的效果。
发明内容
为解决上述技术问题，本发明提供一种根据P值比较不同药物对抗焦虑效果的分析方法和装置。
为实现上述目的，本发明采用的技术方案如下：
本发明第一方面提供一种根据P值比较不同药物对抗焦虑效果的分析方法，该方法包括：S1、确定压力应激模型；S2、将测试样本分为对照组和药物组，并在所述对照组和药物组接受所述压力应激模型后进行至少两种行为学测试，得到对照组测试结果和药物组测试结果；其中，位于所述对照组的测试样本不给药，位于所述药物组的测试样本给药；所述待测药物的种类为至少三种，所述药物组的组数为至少三组；每个所述行为学测试包括至少一个行为参数；S3、将所述药物组的测试结果与对照组测试结果进行单因素方差分析，获得所述每组所述药物组在每个行为参数中的P值；S4、对所述每组所述药物组在每个行为参数中的P值，以同比例的*号个数进行概率程度标记；S5、统计每种待测药物获得的*号总数，并对所述待测药物进行抗焦虑效果排序。
进一步的，在P<0.05的情况下，计为*；在P<0.01的情况下，计为**；在P<0.001的情况下，计为***。
进一步的，在所述确定压力应激模型中，所述压力应激模型包括将所述对照组和药物组中的测试样本悬尾30min、足底电击0.5mA×2s，一共10个循环，每个循环间隔10s和束缚1h，连续四天；所述行为学测试包括旷场实验、高架十字迷宫实验、黑白箱实验、悬尾实验。
进一步的，所述对照组测试结果和药物组测试结果包括在旷场实验的中间区时间、中间进入次数和总移动距离，在高架十字迷宫实验中的开放臂时间、总静止时间，在黑白箱实验中的白箱时间、白箱/黑箱穿越次数、潜伏时间以及在悬尾实验中的静止时间。
进一步的，所述药物组的数量与所述待测药物的种类数量一致。
进一步的，在所述确定压力应激模型之前，还包括：对所述对照组和药物组的测试样本进行连续四周灌胃；其中，所述对照组的测试样本灌胃所用的是生理盐水，所述药物组的测试样本灌胃所用的是待测药物。
本发明第二方面提供一种电子设备，包括：至少一个处理器；以及，与所述至少一个处理器通信连接的存储器；其中，所述存储器存储有可被所述至少一个处理器执行的指令，所述指令被所述至少一个处理器执行，以使所述至少一个处理器能够执行如上述的根据P值比较不同药物对抗焦虑效果的分析方法。
本发明第三方面提供一种计算机可读存储介质，存储有计算机程序，所述计算机程序被处理器执行时实现上述的根据P值比较不同药物对抗焦虑效果的分析方法。
相较于现有技术，本发明提供的技术方案至少具有以下优点：
本发明提供一种根据P值比较不同药物对抗焦虑效果的分析方法和装置，主要针对研究对象为小鼠的抗焦虑效果进行评价，对要进行多种行为学测试的研究提供一种综合分析抗焦虑效果的方法，该方法可以综合分析3种及3种以上药物的抗焦虑效果，为开发和确定使用哪一种药物提供基础。
附图说明
图1为本发明实施例以行为学测试中对待测药物2-FL、Cerebiome+R215和2-FL+Cerebiome+R215的结果；
图2为本发明实施例以行为测试结果对待测药物2-FL、Cerebiome+R215和2-FL+Cerebiome+R215根据P值标注*号的汇总图；
图3为本发明提供的一种电子设备的结构示意图。
具体实施方式
发明人发现，目前的临床研究，由于研究对象是人类，采用的调查问卷的方式，所得的抗焦虑效果只能提供参考，因为我们大多数的实验还是主要围绕小鼠进行。而现有的动物实验研究中，由于小鼠无法像人类一样直接表达情绪，所以我们只能采取多种行为测试，反应小鼠的情绪。但现有的研究通过单因素方差分析后，只得到了在某个具体的行为参数中，两种药物抗焦虑效果的比较，这种情况就可能存在不同行为中药物的效果表达存在差异，没有综合的分析不同药物的效果。
本发明旨在综合评估三种及三种以上药物的抗焦虑效果，获得一个具体的药效排名，为需要的人提供参考。
本发明第一方面提供一种根据P值比较不同药物对抗焦虑效果的分析方法，该方法包括：S1、确定压力应激模型；S2、将测试样本分为对照组和药物组，并在所述对照组和药物组接受所述压力应激模型后进行至少两种行为学测试，得到对照组测试结果和药物组测试结果；其中，位于所述对照组的测试样本不给药，位于所述药物组的测试样本给药；所述待测药物的种类为至少三种，所述药物组的组数为至少三组；每个所述行为学测试包括至少一个行为参数；S3、将所述药物组的测试结果与对照组测试结果进行单因素方差分析，获得所述每组所述药物组在每个行为参数中的P值；S4、对所述每组所述药物组在每个行为参数中的P值，以同比例的*号个数进行概率程度标记；S5、统计每种待测药物获得的*号总数，并对所述待测药物进行抗焦虑效果排序。
以下介绍本发明的优选实施例，使其技术内容更加清楚和便于理解。本发明可以通过许多不同形式的实施例来得以体现，本发明的保护范围并非仅限于文中提到的实施例。
在本发明中使用了很多术语，除非另有说明，否则本文中使用的科学和技术名词具有本领域技术人员所通常理解的含义。为了更清楚一致地理解本发明，下面提供相关术语的定义和解释。
如本文所使用的术语“灌胃”、“灌胃给药”是指一般给药前，实验动物禁食12h～16h，之后将动物固定，使用注射器和灌胃针，将药液由动物口直接注入到动物胃中。
如本文所使用的术语“旷场实验”、“open field test”又称敞箱实验，是评价实验动物在新异环境中自主行为、探究行为与紧张度的一种方法。以实验动物在新异环境之中某些行为的发生频率和持续时间等，反应实验动物在陌生环境中的自主行为与探究行为。旷场实验观察研究实验动物神经精神变化、进入开阔环境后的各种行为，例如动物对新开阔环境的恐惧而主要在周边区域活动，在中央区域活动较少，但动物的探究特性又促使其产生在中央区 域活动的动机，也可观察由此而产生的焦虑心理。中枢兴奋药物可以明显增加自主的活动而减少探究行为，一定剂量的抗精神病药物可以减少探究行为而不影响自主活动。
如本文所使用的术语“高架十字迷宫实验”、“elevatedplus maze”是指利用动物对新异环境的探究特性和对高悬敞开臂的恐惧形成矛盾冲突行为来考察动物的焦虑状态。高架十字迷宫具有一对开放臂和一对闭合臂，啮齿类动物由于嗜暗性会倾向于在闭合臂中活动，但出于好奇心和探究性又会在开放臂中活动。在面对新奇刺激时,动物同时产生探究的冲动与恐惧，这就造成了探究与回避的冲突行为，从而产生焦虑心理。而抗焦虑药物能明显增加进入开臂的次数与时间。高架十字迷宫被广泛应用于新药开发/筛选/评价、药理学、毒理学、预防医学、神经生物学、动物心理学及行为生物学等多个学科的科学-研究和计算机辅助教学等领域，是开展行为学研究尤其是焦虑抑郁研究的经典实验。
如本文所使用的术语“黑白箱实验”、“light and darkbox”是指在明暗箱中，小鼠或大鼠喜欢在暗箱(黑箱)活动，但动物的探究习性促使其试图去探究明箱(白箱)。然而，明箱的亮光刺激又抑制动物在明箱的探究活动。抗焦虑可解除这种抑制作用。
如本文所使用的术语“悬尾实验”，“Tail suspension test”是一种经典而又能快速评价抗抑郁药物、兴奋药物、镇静药物药效的方法。其原理是利用小鼠悬尾后企图逃脱但又无法逃脱，从而放弃挣扎，进入特有的抑郁不动状态，实验过程中记录动物不动时间来反映抑郁状态，抗抑郁药物、兴奋药物能明显地缩短改变其状态。
本发明使用的模式动物为小鼠，并将测试过程中指标异常小鼠剔除(即图1中标注为异常值的)，以加强实验的完整性。
以下将通过具体实施例对本发明进行进一步阐述。
以2-FL、Cerebiome+R215和2-FL+Cerebiome+R215为例。
通过旷场实验、高架十字迷宫实验、黑白箱实验和悬尾实验对待测药物2-FL、Cerebiome+R215和2-FL+Cerebiome+R215进行测试，测试结果如图1和图2所示。
旷场实验：持续四天的压力应激造模结束后一天早8:00将小鼠放入旷场实验室适应1h，保持实验环境安静，其温度湿度与小鼠饲养房间相同。然后将小鼠置于35cm×35cm×30cm的透明箱底面中心位置，同时进行摄像和计时。摄像装备架设在反应箱正上方2m处，其视野可覆盖整个旷场内部。用visuTrack软件对小鼠在旷场内移动的总距离与在中心区域停留时间进行记录，观察10min后停止摄像与记录。将小鼠取出并清洁反应箱内壁及底面，喷75％酒精去除气味，以便下次实验继续使用。
高架十字迷宫实验：实验前将小鼠放入旷场中适应15min，然后把待测小鼠轻柔的放入十字中心，同时进行摄像和记录。每只鼠观察约7min，用visuTrack软件记录小鼠在开放臂 停留的时间。实验结束后将小鼠取出并用75％酒精清洁开放臂及闭合臂，以便下次实验继续使用。
黑白箱实验：黑白箱(45cm×27cm×27cm)中暗箱占二分之一，顶部加盖；明箱占二分之一，亮光照明，两箱之间的隔墙有一个7.5cm×7.5cm的门洞供动物穿过。明暗箱置于Animex活动计数仪上，可同时记录动物的运动活性。动物给药后一定时间置于明箱中央，记录5min内穿箱次数及分布在明箱滞留时间和由明箱首次进入暗箱的潜伏期。
悬尾实验：使用专门的悬尾测试仪，通过固定动物尾部使其头向下悬挂，记录处于该环境的动物产生绝望的不动状态过程中的一系列参数。方法之一：将小鼠尾部后1/3处用胶带固定，悬挂于支架上，头部距离台面15cm，进行摄像，摄像背景与小鼠毛色呈明显反差，白色小鼠采用黑色背景。计时6min后停止，利用小动物行为学分析软件：用visuTrack软件对小鼠后五分钟(1～6min)的静止时间进行统计。
实验过程中我们先进行连续4周的灌胃，对照组灌胃的是生理盐水，小鼠分组：药物A组(A+Stress)、药物B组(B+Stress)、药物C组(C+Stress)和Stress组(VEH+Stress)。待4周灌胃结束后进行压力应激造模，之后进行旷场、高架十字迷宫、黑白箱和悬尾实验。使用Graphpadprism8软件进行单因素方差，Tukey多重比较分析。根据在每一个行为参数中的P值，进行标记，*P<0.05、**P<0.01、***P<0.001。统计不同药物获得*的总数，然后进行排序。
药物A组(A+Stress)的给药药物为2-FL，药物B组(B+Stress)的给药药物为Cerebiome+R215，药物C组(C+Stress)的给药药物为2-FL+Cerebiome+R215。如图1所示，对旷场、高架十字迷宫、黑白箱和悬尾测试结果使用Graphpadprism8软件进行单因素方差，Tukey多重比较分析。在旷场测试中，2-FL+Stress组和2-FL+Cerebiome+R215+Stress组与VEH+Stress组相比，显著增加了中间区时间和中间区进入次数，Cerebiome+R215+Stress组与VEH+Stress组相比，显著增加了中间区时间。在黑白箱测试中，2-FL+Stress组和Cerebiome+R215+Stress组与VEH+Stress组相比，显著增加了白箱时间。在悬尾测试中，2-FL+Stress组、Cerebiome+R215+Stress组和2-FL+Cerebiome+R215+Stress组与VEH+Stress组相比，显著降低了静止时间。
如图2所示，2-FL组(即药物A组)在旷场实验中的中间区时间计为*、中间进入次数计为**，在黑白箱实验中的白箱时间计为*，在悬尾实验中的静止时间计为***，合计*总数为7。
Cerebiome+R215组(即药物B组)在旷场实验中的中间区时间计为*，在黑白箱实验中 的白箱时间计为*，在悬尾实验中的静止时间计为***，合计*总数为5。
药物2-FL+Cerebiome+R215组(即药物C组)在旷场实验中的中间区时间计为**、中间进入次数计为*，在悬尾实验中的静止时间计为***，合计*总数为6。
可以看出，上述待测药物的抗焦虑效果排序：2-FL>2-FL+Cerebiome+R215>Cerebiome+R215。
本发明经过了实验、模拟、使用，证明了分析方法的有效性。结果证明该发明可以综合分析得出不同药物药效的排名。
参考图3，本发明另一实施例提供了一种电子设备，包括：至少一个处理器110；以及，与至少一个处理器通信连接的存储器111；其中，存储器111存储有可被至少一个处理器110执行的指令，指令被至少一个处理器110执行，以使至少一个处理器110能够执行上述任一方法实施例。
其中，存储器111和处理器110采用总线方式连接，总线可以包括任意数量的互联的总线和桥，总线将一个或多个处理器110和存储器111的各种电路连接在一起。总线还可以将诸如外围设备、稳压器和功率管理电路等之类的各种其他电路连接在一起，这些都是本领域所公知的，因此，本文不再对其进行进一步描述。总线接口在总线和收发机之间提供接口。收发机可以是一个元件，也可以是多个元件，比如多个接收器和发送器，提供用于在传输介质上与各种其他装置通信的单元。经处理器110处理的数据通过天线在无线介质上进行传输，进一步，天线还接收数据并将数据传送给处理器110。
处理器110负责管理总线和通常的处理，还可以提供各种功能，包括定时，外围接口，电压调节、电源管理以及其他控制功能。而存储器111可以被用于存储处理器110在执行操作时所使用的数据。
本发明另一实施例涉及一种计算机可读存储介质，存储有计算机程序。计算机程序被处理器执行时实现上述方法实施例。
即，本领域技术人员可以理解，实现上述实施例方法中的全部或部分步骤是可以通过程序来指令相关的硬件来完成，该程序存储在一个存储介质中，包括若干指令用以使得一个设备(可以是单片机，芯片等)或处理器(processor)执行本申请各个实施例上述方法的全部或部分步骤。而前述的存储介质包括：U盘、移动硬盘、只读存储器(ROM，Read-Only Memory)、随机存取存储器(RAM，Random Access Memory)、磁碟或者光盘等各种可以存储程序代码的介质。
本领域的普通技术人员可以理解，上述各实施方式是实现本申请的具体实施例，而在实际应用中，可以在形式上和细节上对其作各种改变，而不偏离本申请的精神和范围。任何本领域技术人员，在不脱离本申请的精神和范围内，均可作各自更动与修改，因此本申请的保护范围应当以权利要求限定的范围为准。

Claims (8)

  1. 一种根据P值比较不同药物对抗焦虑效果的分析方法，其特征在于，该方法包括：
    S1、确定压力应激模型；
    S2、将测试样本分为对照组和药物组，并在所述对照组和药物组接受所述压力应激模型后进行至少两种行为学测试，得到对照组测试结果和药物组测试结果；其中，位于所述对照组的测试样本不给药，位于所述药物组的测试样本给药；所述待测药物的种类为至少三种，所述药物组的组数为至少三组；每个所述行为学测试包括至少一个行为参数；
    S3、将所述药物组的测试结果与对照组测试结果进行单因素方差分析，获得所述每组所述药物组在每个行为参数中的P值；
    S4、对所述每组所述药物组在每个行为参数中的P值，以同比例的*号个数进行概率程度标记；
    S5、统计每种待测药物获得的*号总数，并对所述待测药物进行抗焦虑效果排序。
  2. 根据权利要求1所述的根据P值比较不同药物对抗焦虑效果的分析方法，其特征在于，在P<0.05的情况下，计为*；
    在P<0.01的情况下，计为**；
    在P<0.001的情况下，计为***。
  3. 根据权利要求1所述的根据P值比较不同药物对抗焦虑效果的分析方法，其特征在于，在所述确定压力应激模型中，所述压力应激模型包括将所述对照组和药物组中的测试样本悬尾30min、足底电击0.5mA×2s，一共10个循环，每个循环间隔10s和束缚1h，连续四天；
    所述行为学测试包括旷场实验、高架十字迷宫实验、黑白箱实验、悬尾实验。
  4. 根据权利要求3所述的根据P值比较不同药物对抗焦虑效果的分析方法，其特征在于，所述对照组测试结果和药物组测试结果包括在旷场实验的中间区时间、中间进入次数和总移动距离，在高架十字迷宫实验中的开放臂时间、总静止时间，在黑白箱实验中的白箱时间、白箱/黑箱穿越次数、潜伏时间以及在悬尾实验中的静止时间。
  5. 根据权利要求1所述的根据P值比较不同药物对抗焦虑效果的分析方法，其特征在于，所述药物组的数量与所述待测药物的种类数量一致。
  6. 根据权利要求1所述的根据P值比较不同药物对抗焦虑效果的分析方法，其特征在于，在所述确定压力应激模型之前，还包括：对位于所述对照组和药物组的测试样本进行四周灌胃；其中，所述对照组的测试样本灌胃所用的是生理盐水，所述药物组的测试样本灌胃所用 的是待测药物。
  7. 一种电子设备，其特征在于，包括：
    至少一个处理器；以及，
    与所述至少一个处理器通信连接的存储器；其中，所述存储器存储有可被所述至少一个处理器执行的指令，所述指令被所述至少一个处理器执行，以使所述至少一个处理器能够执行如权利要求1至6中任一所述的根据P值比较不同药物对抗焦虑效果的分析方法。
  8. 一种计算机可读存储介质，存储有计算机程序，其特征在于，所述计算机程序被处理器执行时实现权利要求1至6中任一所述的根据P值比较不同药物对抗焦虑效果的分析方法。
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