现代预防医学

组别	ACE指数	Chao指数	Shannon指数	Simpson指数
SHR雄性组	628.1±108.4	618.8±103.9	3.969±0.310 0	0.072 63±0.023 47
WKY雄性组	675.7±216.0	661.3±205.0	4.133±0.532 9	0.050 22±0.020 84
SHR雌性组	727.7±144.3	718.2±142.2	4.826±0.193 5	0.019 18±0.003 474
WKY雌性组	745.3±141.1	733.6±136.1	4.646±0.433 9	0.033 59±0.026 08

组别	ACE指数	Chao指数	Shannon指数	Simpson指数
SHR雄性组	628.1±108.4	618.8±103.9	3.969±0.310 0	0.072 63±0.023 47
WKY雄性组	675.7±216.0	661.3±205.0	4.133±0.532 9	0.050 22±0.020 84
SHR雌性组	727.7±144.3	718.2±142.2	4.826±0.193 5	0.019 18±0.003 474
WKY雌性组	745.3±141.1	733.6±136.1	4.646±0.433 9	0.033 59±0.026 08

名称	SHR雄性组	WKY雄性组	SHR雌性组	WKY雌性组
Firmicutes	0.840 9±0.123 9	0.558 5±0.088 5^a	0.739 5±0.044 8	0.6344±0.1349^a
Bacteroidota	0.102 7±0.113 8	0.337 5±0.111 4^a	0.214 4±0.064 0	0.280 0±0.129 7
Actinobacteriota	0.044 4±0.040 1	0.073 0±0.055 5	0.032 7±0.017 3	0.052 3±0.028 5
Proteobacteria	0.000 6(0.000 5,0.001 7)	0.000 9(0.000 7,0.001 5)	0.001 6(0.000 8,0.002 4)	0.008 4(0.000 7,0.021 9)
Verrucomicrobiota	0.000 7(0.000 2,0.001 4)	0.001 0(0.000 5,0.001 8)	0.000 3(0.000 0,0.002 1)	0.000 7(0.000 2,0.001 4)
Firmicutes/Bacteroidota（F/B）	11.325 0(7.577 3,45.766 4)	1.320 2^a(1.220 4,1.785 7)	3.099 0(2.922 4,3.672 4)	2.120 3(1.507 0,3.172 1)

名称	SHR雄性组	WKY雄性组	SHR雌性组	WKY雌性组
Firmicutes	0.840 9±0.123 9	0.558 5±0.088 5^a	0.739 5±0.044 8	0.6344±0.1349^a
Bacteroidota	0.102 7±0.113 8	0.337 5±0.111 4^a	0.214 4±0.064 0	0.280 0±0.129 7
Actinobacteriota	0.044 4±0.040 1	0.073 0±0.055 5	0.032 7±0.017 3	0.052 3±0.028 5
Proteobacteria	0.000 6(0.000 5,0.001 7)	0.000 9(0.000 7,0.001 5)	0.001 6(0.000 8,0.002 4)	0.008 4(0.000 7,0.021 9)
Verrucomicrobiota	0.000 7(0.000 2,0.001 4)	0.001 0(0.000 5,0.001 8)	0.000 3(0.000 0,0.002 1)	0.000 7(0.000 2,0.001 4)
Firmicutes/Bacteroidota（F/B）	11.325 0(7.577 3,45.766 4)	1.320 2^a(1.220 4,1.785 7)	3.099 0(2.922 4,3.672 4)	2.120 3(1.507 0,3.172 1)

名称	SHR雄性组	WKY雄性组	SHR雌性组	WKY雌性组
norank_f_Muribaculaceae	0.091 3±0.101 5	0.320 7±0.126 3^a	0.174 7±0.055 8	0.216 4±0.096 0^a
norank_f_norank_o_Clostridia_UCG-014	0.129 3±0.070 0	0.067 3±0.040 9	0.158 3±0.055 5	0.084 5±0.038 0
Lactobacillus	0.099 1±0.071 2	0.013 9±0.008 2	0.055 5±0.031 3^a	0.085 8±0.076 0^b
unclassfied_f_Lachnospiraceae	0.032 5±0.012 6	0.041 1±0.023 5	0.087 6±0.073 5	0.033 7±0.013 8
norank_f_norank_o_RF39	0.036 7±0.024 3	0.036 0±0.014 2	0.057 4±0.030 1	0.021 4±0.015 8^c
Turicibacter	0.206 2(0.169 2,0.252 1)	0.093 9(0.087 1,0.109 6)	0.006 3^a(0.000 7,0.013 8)	0.031 1^a(0.024 6,0.067 6)
Blautia	0.022 5(0.010 6,0.054 9)	0.048 1(0.023 8,0.056 6)	0.074 7(0.055 7,0.098 5)	0.056 1(0.022 6,0.092 1)
Romboutsia	0.104 5(0.085 4,0.127 3)	0.059 9(0.054 4,0.060 5)	0.009 5^a(0.000 8,0.020 6)	0.050 1(0.027 3,0.077 8)
unclassfied_f_Oscillospiraceae	0.035 4(0.032 4,0.049 3)	0.046 9(0.031 1,0.047 5)	0.055 3(0.048 9,0.059 4)	0.027 3(0.022 7,0.065 9)
Bifidobacterium	0.009 5(0.002 6,0.039 4)	0.046 7(0.006 6,0.070 1)	0.000 3(0.000 1,0.001 7)	0.009 0(0.006 4,0.029 8)

名称	SHR雄性组	WKY雄性组	SHR雌性组	WKY雌性组
norank_f_Muribaculaceae	0.091 3±0.101 5	0.320 7±0.126 3^a	0.174 7±0.055 8	0.216 4±0.096 0^a
norank_f_norank_o_Clostridia_UCG-014	0.129 3±0.070 0	0.067 3±0.040 9	0.158 3±0.055 5	0.084 5±0.038 0
Lactobacillus	0.099 1±0.071 2	0.013 9±0.008 2	0.055 5±0.031 3^a	0.085 8±0.076 0^b
unclassfied_f_Lachnospiraceae	0.032 5±0.012 6	0.041 1±0.023 5	0.087 6±0.073 5	0.033 7±0.013 8
norank_f_norank_o_RF39	0.036 7±0.024 3	0.036 0±0.014 2	0.057 4±0.030 1	0.021 4±0.015 8^c
Turicibacter	0.206 2(0.169 2,0.252 1)	0.093 9(0.087 1,0.109 6)	0.006 3^a(0.000 7,0.013 8)	0.031 1^a(0.024 6,0.067 6)
Blautia	0.022 5(0.010 6,0.054 9)	0.048 1(0.023 8,0.056 6)	0.074 7(0.055 7,0.098 5)	0.056 1(0.022 6,0.092 1)
Romboutsia	0.104 5(0.085 4,0.127 3)	0.059 9(0.054 4,0.060 5)	0.009 5^a(0.000 8,0.020 6)	0.050 1(0.027 3,0.077 8)
unclassfied_f_Oscillospiraceae	0.035 4(0.032 4,0.049 3)	0.046 9(0.031 1,0.047 5)	0.055 3(0.048 9,0.059 4)	0.027 3(0.022 7,0.065 9)
Bifidobacterium	0.009 5(0.002 6,0.039 4)	0.046 7(0.006 6,0.070 1)	0.000 3(0.000 1,0.001 7)	0.009 0(0.006 4,0.029 8)

中年期自发性高血压大鼠血压水平、认知功能与肠道菌群特征分析

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柳鉴修 , 杨洋 , 王凯 , 欧阳东岳 , 任磊 , 简蕊霖 , 杨婷 , 沈曦 , 何方 , 程如越

现代预防医学 | 临床与预防 2026,53(4): 753-759

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现代预防医学 |临床与预防 2026 , 53 (4) : 753 -759

中年期自发性高血压大鼠血压水平、认知功能与肠道菌群特征分析

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柳鉴修, 杨洋, 王凯, 欧阳东岳, 任磊, 简蕊霖, 杨婷, 沈曦, 何方, 程如越

作者信息

四川大学华西公共卫生学院/四川大学华西第四医院，四川成都 610041

通讯作者:

程如越，E-mail: ruyuecheng1993@163.com

作者简介:

柳鉴修（2000—），男，硕士在读，研究方向：肠道菌群与健康

Analysis of blood pressure levels, cognitive function, and gutmicrobiota characteristics in SHR rats

Jian-xiu LIU, Yang YANG, Kai WANG, Dong-yue OUYANG, Lei REN, Rui-Lin JIAN, Ting YANG, Xi SHEN, Fang HE, Ru-yue CHENG

Affiliations

West China School of Public Health/West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, China

出版时间: 2026-02-25 doi: 10.20043/j.cnki.MPM.202504210

文章导航

摘要

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目的

探究中年期自发性高血压大鼠（SHR）的血压水平、认知功能和肠道菌群特征。

方法

购入13周龄的SHR及其对照大鼠WKY，随机分为4组，分别为SHR雄性组（n=6），SHR雌性组（n=8），WKY雄性组（n=6），WKY雌性组（n=8），饲养26周后采用尾压法测量大鼠血压水平，采用旷场实验观察大鼠的自主活动能力，采用Morris水迷宫实验观察大鼠的学习与认知功能。实验结束后，收集大鼠粪便，采用16SrRNA测序分析大鼠的肠道菌群特征。

结果

SHR组雄性与雌性大鼠的收缩压均显著高于WKY组（均P<0.01）。旷场实验结果显示，SHR雌鼠的运动平均速度高于WKY雄鼠（P<0.001），而WKY雌鼠的周围区域停留时间高于WKY雄鼠（P<0.05）。水迷宫实验结果显示，SHR训练期的潜伏期时间下降幅度均较WKY大，而WKY雌鼠测试期的潜伏期时间均高于SHR雄鼠和雌鼠（P<0.01;P<0.001）。Beta多样性分析表明四组大鼠的肠道菌群结构存在显著差异（R=0.627 5, P=0.001），且SHR雄鼠呈现出Firmicutes和Turicibacter相对丰度升高的特征，WKY雄鼠呈现出以Bacteroidota、norank_f_Muribaculaceae相对丰度升高的特征（均P<0.05）。相关性分析表明，不同性别的SHR和WKY大鼠的部分肠道菌群相对丰度与血压及行为学指标之间均存在显著关联。

结论

中年期SHR大鼠的血压水平、认知功能和肠道菌群特征具有显著的性别差异，其血压升高、兴奋多动的特点在雌鼠中表现更明显，而肠道菌群组成异常的特点在雄鼠中表现突出，提示性别差异应考虑在高血压与肠道菌群的相关研究中。

关键词

SHR大鼠 / 自发性高血压 / 认知功能 / 肠道菌群 / 性别差异

Abstract

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Objective

To investigate the blood pressure levels, cognitive function, and gut microbiota characteristics of middle-aged spontaneously hypertensive rats (SHR).

Methods

SHR and its control rats WKY aged 13 weeks were purchased and randomly divided into 4 groups, namely SHR male group (n=6), SHR female group (n=8), WKY male group (n=6) and WKY female group (n=8). After 26 weeks of feeding, the blood pressure level of the rats was measured by tail pressure method, and the autonomous activity ability of the rats was observed by open field experiment. The Morris water maze experiment was used to observe the learning and cognitive function of rats. After the experiment, the stool of rats was collected, and the intestinal flora characteristics of rats were analyzed by 16SrRNA sequencing.

Results

The systolic blood pressure of male and female rats in SHR group was significantly higher than that in WKY group (all P<0.01). The results of open field test showed that the average speed of SHR female rats was higher than that of WKY male rats (P<0.001), while the residence time in the surrounding area of WKY female rats was higher than that of WKY male rats (P<0.05). The results of water maze test showed that the latency time of SHR during training decreased more than that of WKY, and the latency time of WKY female rats during testing was higher than that of SHR male and female rats (P<0.01; P<0.001). Beta diversity analysis showed that there were significant differences in the structure of intestinal flora among the four groups of rats (R=0.627 5, P=0.001), and the relative abundance of Firmicutes and Turicibacter was increased in SHR males, while that of Bacteroidota and norank_f_Muribaculaceae was increased in WKY males (all P<0.05). Correlation analysis revealed significant associations between the relative abundance of certain gut microbiota and blood pressure as well as behavioral indicators in SHR and WKY rats of different genders.

Conclusion

There are significant gender differences in blood pressure levels, cognitive function, and gut microbiota characteristics among middle-aged SHR rats. The elevated blood pressure and hyperactivity characteristics are more pronounced in female rats, while the abnormal gut microbiota composition is more prominent in male rats. This suggests that gender differences should be considered in studies related to hypertension and gut microbiota.

Key words

SHR rat / Spontaneous hypertension / Cognitive Function / Gut microbiota / Gender difference

引用本文

柳鉴修, 杨洋, 王凯, 欧阳东岳, 任磊, 简蕊霖, 杨婷, 沈曦, 何方, 程如越. 中年期自发性高血压大鼠血压水平、认知功能与肠道菌群特征分析. 现代预防医学, 2026 , 53 (4) : 753 -759 . DOI: 10.20043/j.cnki.MPM.202504210

Jian-xiu LIU, Yang YANG, Kai WANG, Dong-yue OUYANG, Lei REN, Rui-Lin JIAN, Ting YANG, Xi SHEN, Fang HE, Ru-yue CHENG. Analysis of blood pressure levels, cognitive function, and gutmicrobiota characteristics in SHR rats[J]. Modern Preventive Medicine, 2026 , 53 (4) : 753 -759 . DOI: 10.20043/j.cnki.MPM.202504210

正文

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1　前言

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高血压是全球面临的重要公共卫生问题，是全球疾病负担和全球死亡率的重要因素，其患病率仍不断升高^[1]。高血压的患病率随年龄的增长而加速，中年期属于高发期，受生活行为习惯、膳食、运动、激素等较多因素影响，其患病率存在明显的性别差异^[2-3]。高血压的发病机制较为复杂，较高的收缩压和舒张压对中年人群的情绪和认知功能也存在显著影响，肠道菌群作为新的方向逐渐被重视^[4-7]。研究发现，高血压患者普遍存在肠道菌群紊乱，而肠道菌群本身还存在性别差异，但目前有关高血压患者的肠道菌群、认知功能特征的结论不一致，尤其是在性别方面的差异仍需要进一步探索^[8-13]。

自发性高血压大鼠（Spontaneously Hypertensive Rats，SHR）因其高血压的自发性和高发病率，被广泛用于高血压及其并发症的研究。该动物模型与人类高血压相似，无需其它干预，自发稳定形成高血压，成年时收缩压达200 mmHg。SHR是由Wistar-Kyoto（WKY）选育而来，因而WKY常被选用为SHR的对照品系。此外，SHR还因其在学习和认知功能上的异常，常用于行为和认知方面的研究。

因此，本研究将13周龄的WKY及SHR正常饲养至39周龄，期间不做干预，探究中年期的SHR和WKY的血压水平、行为认知和肠道菌群方面的特征及差异，研究肠道菌群、高血压和认知功能的相关性，同时探讨性别差异在高血压及其并发症防治中的重要意义。

2　材料与方法

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2.1　主要仪器设备

电子天平（赛多利斯科学仪器有限公司）；Morris水迷宫分析系统WMT-100（成都泰盟软件有限公司）；旷场实验分析系统OFT-100（成都泰盟软件有限公司）；medlab大鼠无创血压测量系统（南京卡尔文生物科技有限公司）。

2.2　实验动物及分组

购入13周龄的SHR及其对照大鼠WKY，随机分为4组，分别为SHR雄性组（n=6），SHR雌性组（n=8），WKY雄性组（n=6），WKY雌性组（n=8），所有大鼠购买于维通利华实验动物技术有限公司，总数为28只，所有实验动物遵循国家实验动物保护和使用指南，并通过四川大学华西公共卫生学院/华西第四医院伦理委员会批准（批准号：Gwll2022057）。大鼠饲养于明暗交替12 h/12 h、温度20～22 ℃、相对湿度（50±10）%的无特殊病原体（specific pathogen free, SPF）级动物房，自由摄食、饮水。

2.3　Morris水迷宫实验

Morris水迷宫实验第1~5天为隐匿平台训练，每天进行4次检测，利用摄像机和WMT-100系统记录逃避潜伏期时间和运动轨迹，4次检测的均值记为训练日潜伏期，第6 d采用空间探索实验，撤掉圆形平台将大鼠从NE象限放入水池，记录大鼠首次到达原平台位置的时间，记为测试日的潜伏期，以检测大鼠的空间位置感与空间记忆力。

2.4　旷场实验

使用边长80 cm×80 cm的挡板组装成封闭式旷场，将旷场地划分为9个区域，最中间的为中心区域，角落区域与边缘区域合成为周边区域。采用OFT-100软件记录大鼠的运动总距离及平均速度，每只大鼠旷场实验时间为5 min，在实验结束后，收集粪便，清理旷场并等消毒剂完全干燥后放入下一只。在实验过程中记录静止时间、运动时间、运动距离、中心活动时间及距离、角落活动时间及距离、边缘活动时间及距离、排便次数及排尿次数。

2.5　大鼠血压检测

大鼠血压测量方法选择尾压法（Tail-cuff法）。将传感器套在大鼠尾部，通过充气、放气对尾动脉加压和释压的同时监测血流信号，得出血压值。使用前需提前加热装置对仪器环境加热，保持温热的环境，打开把老鼠固定在特定的保温装置内，尾巴上套上传感器，待脉搏波稳定后，重复测量5次，记录收缩压和舒张压并求均值。

2.6　粪便DNA提取与16 s扩增子测序分析

在行为学实验后用粪便收集器收集各组大鼠新鲜粪便，分装好的样品用无菌塑料袋包装放在干冰上立即运至实验室，存储在-80 ℃超低温冰箱用于DNA高通量测序分析。采用FastPure Stool DNA Isolation Kit（Magnetic bead）（MJYH, shanghai, China）提取大鼠粪便样品的DNA。完成基因组DNA抽提后，利用1%琼脂糖凝胶电泳检测抽提的基因组DNA。将提取的DNA进行PCR扩增和测序文库构建，测序获得的PE reads经样本拆分后，通过质量控制和双端序列拼接生成优化数据，经降噪处理得到ASV代表序列及丰度信息。基于ASV进行α/β多样性分析及门、属水平群落结构分析。粪便DNA提取与16S rRNA测序由上海美吉生物医药科技有限公司完成，数据分析依托其云平台实现。

2.7　统计分析方法

使用SPSS 26.0对数据进行统计分析，Graphpad Prism 9.5绘制图表，Rstudio 4.4.1做相关性分析和绘图。所有计量资料均使用均数±标准差（

）表示。对不服从正态分布的数据以中位数和四分位数间距表示。服从正态分布的数据采用Two-way ANOVA检验，采用Tukey多重比较进行组间的两两分析。不服从正态分布的数据采用Kruskal-Wallis H进行非参数检验，采用Spearman秩相关进行相关性分析。设检验水准α=0.05，所有检验均为双侧检验。

3　结果

收起

3.1　大鼠血压测量结果

各组大鼠的血压测量结果见图1。在雄性和雌性中，SHR组大鼠的SBP值均高于WKY组，差异有统计学意义（F=18.57.P<0.001）；SHR雄性组的DBP值高于SHR雌性组（P<0.05）,差异有统计学意义；SHR组大鼠的DBP值均高于WKY组，但差异无统计学意义（P>0.05）。

3.2　旷场实验结果

各组大鼠的旷场实验结果见图2。各组大鼠的排便数量存在数量差异，但无统计学意义（U=5.50,P>0.05）；SHR雌性组的运动总距离和平均速度高于WKY雄性组（P<0.001），WKY雌性组周围区域运动时间高于WKY雄性组，差异有统计学意义（P<0.05）。

3.3　Morris水迷宫实验结果

水迷宫训练期的实验结果见图3。训练期开展定位航行实验，从Day1到Day5，所有组的逃逸潜伏期时间都有不同程度的下降，Day1各组潜伏期时间差异较小且无统计学意义（F=0.550 9,P>0.05）；Day2到Day5训练期间，SHR雄性和雌性组的潜伏期下降幅度均较WKY组更大，差异具有统计学意义（P<0.05;P<0.01<;P<0.001）。

测试期的空间搜索实验结果见图4。SHR大鼠和WKY大鼠正式训练时间存在差异（F=11.29,P<0.001),SHR雄性组和雌性组的潜伏期时间更短，均低于WKY雌性组，差异具有统计学意义（P<0.01；P<0.001）。

3.4　肠道菌群多样性与群落结构

3.4.1　Alpha多样性

各组大鼠的α多样性指数见表1。各组大鼠在ACE指数、Chao指数、Shannon指数、Simpson指数上存在差异但无统计学意义（P>0.05）。

3.4.2　Beta多样性

PCoA分析结果见图5，四个组菌群结构差异有统计学意义（R=0.627 5，P=0.001），表明各组大鼠肠道菌群的群落聚散程度存在显著不同。

3.4.3　门水平群落物种差异分析

门水平上肠道菌群相对丰度柱状图见图6，组间比较结果见表2。各组的Firmicutes和Bacteroidota均处于主导地位。SHR雄性组Firmicutes相对丰度高于WKY雄性组和WKY雌性组（P<0.05)，Bacteroidota丰度低于WKY雄性组（P<0.05)，Firmicutes与Bacteroidota相对丰度的比值（F/B）显著高于WKY雄性组，差异有统计学意义（P<0.05)。

3.4.4　属水平群落物种差异分析

如图7和表3所示，SHR雄性组的norank_f_Muribaculaceae相对丰度低于WKY雄性组和WKY雌性组（P<0.05)，Lactobacillus相对丰度高于SHR雌性组（P<0.05)，Turicibacter相对丰度高于SHR雌性组和WKY雌性组（P<0.05)，Romboutsia相对丰度高于SHR雌性组（P<0.05)；WKY雄性组的Lactobacillus相对丰度低于WKY雌性组（P<0.05)，SHR雌性组的norank_f_norank_o_RF39相对丰度高于WKY雌性，差异均有统计学意义（P<0.05)。

3.4.5　相关性分析

将SHR和WKY组的雌鼠和雄鼠的肠道菌群门水平和属水平的细菌丰度与SBP、DBP、旷场、水迷宫数据做相关性分析，结果见图8。在SHR雄鼠中，Verrucomicrobiota与DBP呈负相关（P<0.05），norank_f_norank_o_Clostridia_UCG-014、Romboutsia与DBP呈正相关（P<0.05），Firmicutes与Proteobacteria与运动总距离及运动平均速度呈负相关（P<0.05）；在SHR雌鼠中，Proteobacteria、unclassfied_f_Oscillospiraceae与SBP呈负相关（P<0.05；P<0.01），norank_f_norank_o_Clostridia_UCG-014与DBP呈正相关（P<0.01），Blautia与运动总距离和运动平均速度呈负相关（P<0.01）；在WKY雄鼠中，Firmicutes、Bacteroidota、Verrucomicrobiota与SBP呈负相关（P<0.001），Actinobacteriota、Bifidobacterium与DBP呈正相关（P<0.001），Lactobacillus与DBP呈负相关（P<0.05），Bifidobacterium与运动总距离及运动平均速度呈正相关（P<0.05），Firmicutes、Bacteroidota、Verrucomicrobiota、unclassfied_f_Lachnospiraceae与正式实验潜伏期时间呈正相关（P<0.05;P<0.001），norank_f_norank_o_Clostridia_UCG-014与周围区域静止时间呈正相关（P<0.05）；在WKY雌鼠中，Turicibacter、Romboutsia与周围区域静止时间呈正相关（P<0.05;P<0.01），unclassfied_f_Lachnospiraceae与正式实验潜伏期时间呈正相关（P<0.05）。

4　讨论

收起

目前利用SHR大鼠研究干预物改善高血压效果的文献较多，但针对不同性别的SHR和WKY大鼠的血压作系统对比的基础研究仍然较少。本研究发现不同性别SHR大鼠和WKY大鼠的血压值没有显著差异，表明动物品系是影响高血压表型的主要因素。尽管SHR大鼠的收缩压显著高于WKY大鼠，但舒张压与WKY大鼠相比无显著差异。有研究也发现，SHR大鼠与WKY大鼠在舒张压上没有显著差异，这可能与WKY大鼠的遗传不稳定性有关^[14]。此外，尾压法在测量大鼠血压时可能受到温度、大鼠的活跃性等因素影响，对舒张压的检测会存在敏感性偏低的情况^[15-16]。

旷场实验能反映大鼠面对新环境的情绪变化和自主运动能力。有研究表明SHR雄鼠在旷场中的运动路程、平均速度都显著高于WKY大鼠，具有明显的多动和易冲动的特点，这与本研究结果一致。为了探究性别差异，本研究进一步发现SHR和WKY雌鼠的运动能力普遍高于雄鼠，反映出雌性对陌生环境的反应更为敏感，高血压对雌性的情绪影响可能更大。Morris水迷宫实验可以检测大鼠的空间位置感和空间记忆力，该研究也发现SHR雄鼠和WKY雄鼠相比，其水迷宫潜伏期更短^[17]。本研究进一步发现SHR和WKY雌鼠水迷宫潜伏期较雄鼠更短，反映出性别也会影响空间记忆和学习能力，同时表明高血压对学习和认知能力产生了影响，且对雌性影响更大。

研究表明，自发性高血压能造成肠道菌群紊乱，主要体现在F/B值显著增加，同时Firmicutes和产乳酸的菌群相对丰度明显增加，Bacteroidota减少^[18-19]，这些发现与本研究结果一致。此外，本研究发现不同性别大鼠的肠道菌群组成存在明显差异，且SHR雄鼠肠道菌群更具有独特性。以往研究多聚焦肠道菌群与高血压的整体关联，但较少关注性别差异。本研究发现，无论是SHR还是WKY大鼠，雌性和雄性的肠道菌群与血压水平、行为表型的关联性并不完全相同，说明了性别差异在菌群-宿主互作中的关键作用。此外，部分相同菌群在不同性别中与血压或认知相关行为指标的关联方向相反，如WKY中Firmicutes、Bacteroidota与雄鼠和雌鼠SBP、DBP的相关性明显相反，Bifidobacterium与雄鼠和雌鼠的DBP及运动距离和平均速度的相关性明显相反。研究表明，性激素会参与血压、情绪、认知水平的调节^[20-21]，提示未来需要关注性别在高血压与肠道菌群相关研究中的潜在作用。然而，本研究发现，也有一些菌群与血压、行为的相关性不受性别影响，如norank_f_norank_o_Clostridia_UCG-014，在SHR中，与雄鼠和雌鼠的DBP均具有显著的正相关；而在WKY中，与雄鼠和雌鼠的周围区域静止时间均具有显著的正相关；提示该菌在血压与行为方面可能具有较稳定的调节作用。

本研究发现中年期SHR大鼠的血压水平、认知功能和肠道菌群特征以及三者之间的关联均具有显著的性别差异，其血压升高、兴奋多动的特点在雌鼠中表现更明显，而肠道菌群组成异常的特点在雄鼠中表现突出，提示性别差异应考虑在高血压与肠道菌群的相关研究中。但是，由于SHR大鼠是自发性高血压疾病模型，本研究的观察性设计无法区分肠道菌群的改变是高血压及其行为表型的原因，还是其结果，或是一种伴随现象。下一步研究可通过抗生素清除菌群、粪菌移植实验等进一步明确肠道菌群与高血压及其行为障碍的因果关系。

基金

收起

国家自然科学基金青年科学基金(82204037)
中国博士后科学基金(2022M712228)
四川大学专职博士后科研基金(2022SCU12026)

参考文献

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文献

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2026年第53卷第4期

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文章信息

doi: 10.20043/j.cnki.MPM.202504210

接收时间：2025-04-10
首发时间：2026-11-02
出版时间：2026-02-25

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收稿日期：2025-04-10

基金

国家自然科学基金青年科学基金(82204037)

中国博士后科学基金(2022M712228)

四川大学专职博士后科研基金(2022SCU12026)

作者信息

四川大学华西公共卫生学院/四川大学华西第四医院，四川成都 610041

通讯作者:

程如越，E-mail: ruyuecheng1993@163.com

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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组别	ACE指数	Chao指数	Shannon指数	Simpson指数
SHR雄性组	628.1±108.4	618.8±103.9	3.969±0.310 0	0.072 63±0.023 47
WKY雄性组	675.7±216.0	661.3±205.0	4.133±0.532 9	0.050 22±0.020 84
SHR雌性组	727.7±144.3	718.2±142.2	4.826±0.193 5	0.019 18±0.003 474
WKY雌性组	745.3±141.1	733.6±136.1	4.646±0.433 9	0.033 59±0.026 08

组别

ACE指数

Chao指数

Shannon指数

Simpson指数

SHR雄性组

628.1±108.4

618.8±103.9

3.969±0.310 0

0.072 63±0.023 47

WKY雄性组

675.7±216.0

661.3±205.0

4.133±0.532 9

0.050 22±0.020 84

SHR雌性组

727.7±144.3

718.2±142.2

4.826±0.193 5

0.019 18±0.003 474

WKY雌性组

745.3±141.1

733.6±136.1

4.646±0.433 9

0.033 59±0.026 08

名称	SHR雄性组	WKY雄性组	SHR雌性组	WKY雌性组
Firmicutes	0.840 9±0.123 9	0.558 5±0.088 5^a	0.739 5±0.044 8	0.6344±0.1349^a
Bacteroidota	0.102 7±0.113 8	0.337 5±0.111 4^a	0.214 4±0.064 0	0.280 0±0.129 7
Actinobacteriota	0.044 4±0.040 1	0.073 0±0.055 5	0.032 7±0.017 3	0.052 3±0.028 5
Proteobacteria	0.000 6(0.000 5,0.001 7)	0.000 9(0.000 7,0.001 5)	0.001 6(0.000 8,0.002 4)	0.008 4(0.000 7,0.021 9)
Verrucomicrobiota	0.000 7(0.000 2,0.001 4)	0.001 0(0.000 5,0.001 8)	0.000 3(0.000 0,0.002 1)	0.000 7(0.000 2,0.001 4)
Firmicutes/Bacteroidota（F/B）	11.325 0(7.577 3,45.766 4)	1.320 2^a(1.220 4,1.785 7)	3.099 0(2.922 4,3.672 4)	2.120 3(1.507 0,3.172 1)

名称

SHR雄性组

WKY雄性组

SHR雌性组

WKY雌性组

Firmicutes

0.840 9±0.123 9

0.558 5±0.088 5^a

0.739 5±0.044 8

0.6344±0.1349^a

Bacteroidota

0.102 7±0.113 8

0.337 5±0.111 4^a

0.214 4±0.064 0

0.280 0±0.129 7

Actinobacteriota

0.044 4±0.040 1

0.073 0±0.055 5

0.032 7±0.017 3

0.052 3±0.028 5

Proteobacteria

0.000 6(0.000 5,0.001 7)

0.000 9(0.000 7,0.001 5)

0.001 6(0.000 8,0.002 4)

0.008 4(0.000 7,0.021 9)

Verrucomicrobiota

0.000 7(0.000 2,0.001 4)

0.001 0(0.000 5,0.001 8)

0.000 3(0.000 0,0.002 1)

0.000 7(0.000 2,0.001 4)

Firmicutes/Bacteroidota（F/B）

11.325 0(7.577 3,45.766 4)

1.320 2^a(1.220 4,1.785 7)

3.099 0(2.922 4,3.672 4)

2.120 3(1.507 0,3.172 1)

名称	SHR雄性组	WKY雄性组	SHR雌性组	WKY雌性组
norank_f_Muribaculaceae	0.091 3±0.101 5	0.320 7±0.126 3^a	0.174 7±0.055 8	0.216 4±0.096 0^a
norank_f_norank_o_Clostridia_UCG-014	0.129 3±0.070 0	0.067 3±0.040 9	0.158 3±0.055 5	0.084 5±0.038 0
Lactobacillus	0.099 1±0.071 2	0.013 9±0.008 2	0.055 5±0.031 3^a	0.085 8±0.076 0^b
unclassfied_f_Lachnospiraceae	0.032 5±0.012 6	0.041 1±0.023 5	0.087 6±0.073 5	0.033 7±0.013 8
norank_f_norank_o_RF39	0.036 7±0.024 3	0.036 0±0.014 2	0.057 4±0.030 1	0.021 4±0.015 8^c
Turicibacter	0.206 2(0.169 2,0.252 1)	0.093 9(0.087 1,0.109 6)	0.006 3^a(0.000 7,0.013 8)	0.031 1^a(0.024 6,0.067 6)
Blautia	0.022 5(0.010 6,0.054 9)	0.048 1(0.023 8,0.056 6)	0.074 7(0.055 7,0.098 5)	0.056 1(0.022 6,0.092 1)
Romboutsia	0.104 5(0.085 4,0.127 3)	0.059 9(0.054 4,0.060 5)	0.009 5^a(0.000 8,0.020 6)	0.050 1(0.027 3,0.077 8)
unclassfied_f_Oscillospiraceae	0.035 4(0.032 4,0.049 3)	0.046 9(0.031 1,0.047 5)	0.055 3(0.048 9,0.059 4)	0.027 3(0.022 7,0.065 9)
Bifidobacterium	0.009 5(0.002 6,0.039 4)	0.046 7(0.006 6,0.070 1)	0.000 3(0.000 1,0.001 7)	0.009 0(0.006 4,0.029 8)

名称

SHR雄性组

WKY雄性组

SHR雌性组

WKY雌性组

norank_f_Muribaculaceae

0.091 3±0.101 5

0.320 7±0.126 3^a

0.174 7±0.055 8

0.216 4±0.096 0^a

norank_f_norank_o_Clostridia_UCG-014

0.129 3±0.070 0

0.067 3±0.040 9

0.158 3±0.055 5

0.084 5±0.038 0

Lactobacillus

0.099 1±0.071 2

0.013 9±0.008 2

0.055 5±0.031 3^a

0.085 8±0.076 0^b

unclassfied_f_Lachnospiraceae

0.032 5±0.012 6

0.041 1±0.023 5

0.087 6±0.073 5

0.033 7±0.013 8

norank_f_norank_o_RF39

0.036 7±0.024 3

0.036 0±0.014 2

0.057 4±0.030 1

0.021 4±0.015 8^c

Turicibacter

0.206 2(0.169 2,0.252 1)

0.093 9(0.087 1,0.109 6)

0.006 3^a(0.000 7,0.013 8)

0.031 1^a(0.024 6,0.067 6)

Blautia

0.022 5(0.010 6,0.054 9)

0.048 1(0.023 8,0.056 6)

0.074 7(0.055 7,0.098 5)

0.056 1(0.022 6,0.092 1)

Romboutsia

0.104 5(0.085 4,0.127 3)

0.059 9(0.054 4,0.060 5)

0.009 5^a(0.000 8,0.020 6)

0.050 1(0.027 3,0.077 8)

unclassfied_f_Oscillospiraceae

0.035 4(0.032 4,0.049 3)

0.046 9(0.031 1,0.047 5)

0.055 3(0.048 9,0.059 4)

0.027 3(0.022 7,0.065 9)

Bifidobacterium

0.009 5(0.002 6,0.039 4)

0.046 7(0.006 6,0.070 1)

0.000 3(0.000 1,0.001 7)

0.009 0(0.006 4,0.029 8)