中国中药杂志

基于miR-34a-5p/SIRT1信号通路探究SD大鼠高龄父代对子代学习能力的影响及五子衍宗丸的干预作用

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刘子豪 ¹^,² , 萧闵 ²^,³^,^* , 江晓翠 ²^,³ , 潘琴 ⁵ , 邓朝阳 ²^,⁴ , 祝中意 ¹^,² , 曹继刚 ¹^,²^,^*

中国中药杂志 | 药理 2026,51(1): 250-259

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中国中药杂志 |药理 2026 , 51 (1) : 250 -259

基于miR-34a-5p/SIRT1信号通路探究SD大鼠高龄父代对子代学习能力的影响及五子衍宗丸的干预作用

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刘子豪¹^,², 萧闵²^,³^,^*, 江晓翠²^,³, 潘琴⁵, 邓朝阳²^,⁴, 祝中意¹^,², 曹继刚¹^,²^,^*

作者信息

^1．湖北中医药大学中医学院，湖北武汉 430065

^2．湖北时珍实验室，湖北武汉 430065

^3．湖北中医药大学实验中心，湖北武汉 430065

^4．湖北中医药大学基础医学院，湖北武汉 430065

^5．湖北省妇幼保健院，湖北武汉 430070

通讯作者:

曹继刚，博士，主任医师，教授，博士生导师，主要从事中医藏象理论及其应用、中医泌尿生殖系统理论及其临床研究，E-mail: 774941339@qq.com；

萧闵，博士，副研究员，主要从事动物模型及中西医结合防治不孕不育研究，E-mail: 531637551@qq.com

Influences of aged male parents on learning ability of offspring in SD rats and intervention effect of Wuzi Yanzong Pills based on miR-34a-5p/SIRT1 signaling pathway

Zi-hao LIU¹^,², Min XIAO²^,³^,^*, Xiao-cui JIANG²^,³, Qin PAN⁵, Chao-yang DENG²^,⁴, Zhong-yi ZHU¹^,², Ji-gang CAO¹^,²^,^*

Affiliations

^1.School of Chinese Medicine, Hubei University of Chinese Medicine, Wuhan 430065, China

^2.Hubei Shizhen Laboratory, Wuhan 430065, China

^3.Experimental Center, Hubei University of Chinese Medicine, Wuhan 430065, China

^4.School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China

^5.Maternal and Child Health Hospital of Hubei Province, Wuhan 430070, China

出版时间: 2026-01-01 doi: 10.19540/j.cnki.cjcmm.20250916.801

文章导航

摘要

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为探究高龄父代基于微小RNA-34a-5p（miR-34a-5p）/沉默信息调节因子1（SIRT1）信号通路对子代学习能力的影响及五子衍宗丸的干预作用。因此使用32只15月龄SD雄鼠，随机分为高龄模型组、高龄模型+五子衍宗丸高剂量组、高龄模型+五子衍宗丸低剂量组、高龄模型+维生素C组，每组8只，另设8只3月龄SD雄鼠为低龄对照组，五子衍宗丸低、高剂量组分别给予五子衍宗丸2、8 g·kg^-1饲料喂养，维生素C组给予维生素C（100 mg·kg^-1）饲料，低龄对照组和高龄模型组给予普通饮食，连续饲养12周后，与3月龄雌鼠，1∶1合笼5 d，完成后统计受精率，全自动精子分析仪检测高龄大鼠精子活力及数量，苏木素-伊红（HE）染色评估睾丸生精功能；β-半乳糖苷酶染色检测大鼠睾丸附睾组织衰老细胞；荧光定量PCR（qPCR）检测大鼠睾丸组织miR-34a-5p表达；仔鼠出生1、30 d检测胎产数、体质量、身长，评估子代一般发育情况。将仔鼠喂养至30日龄，水迷宫评估子代学习能力；尼氏染色评估仔鼠海马神经元数量；qPCR检测仔鼠海马组织miR-34a-5p表达；Western blot检测子代海马组织脑源性神经营养因子（BDNF）/SIRT1蛋白。结果显示与低龄对照组比较，高龄模型组受精率、胎产数、精子活力、精子数量及睾丸生精功能，均显著降低或减少（P<0.01），睾丸附睾组织衰老细胞增加，精子中miR-34a-5p表达水平显著上升；30日龄子代生长发育减慢、海马神经元数量显著减少、海马miR-34a-5p表达量显著上升、海马SIRT1、BDNF蛋白含量显著下降（P<0.01），子代学习记忆能力显著降低（P<0.01）；与高龄模型组比较，五子衍宗丸高剂量组、维生素C组，受精率、胎产数、精子活力、精子数量及睾丸生精功能，均显著升高（P<0.05），30日龄子代生长发育加快、海马神经元数量显著增多、海马BDNF蛋白含量显著升高（P<0.05），子代学习记忆能力显著升高（P<0.05）；与维生素C组比较，五子衍宗丸高剂量组子代生长发育显著加快（P<0.05）、受精率、胎产数均显著升高（P<0.05），学习记忆能力显著增加（P<0.05）。由此表明五子衍宗丸能够改善大鼠高龄模型的睾丸生精功能障碍及精子质量，进而改善子代的学习记忆能力，其内在机制可能是通过调控miR-34a-5p的表达延缓睾丸生精细胞衰老，并通过miR-34a-5p介导的代际传递机制改善子代的学习记忆能力。

关键词

高龄父代 / 五子衍宗丸 / miR-34a-5p/SIRT1

Abstract

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This study aims to investigate the effects of aged male parents on the learning ability of offspring and the intervention effect of Wuzi Yanzong Pills based on the microRNA-34a-5p (miR-34a-5p)/silent information regulator 1 (SIRT1) signaling pathway. Thirty-two SD male rats of 15 months old were randomized into aged model, model+high-dose (8 g·kg^-1) Wuzi Yanzong Pills, model+low-dose (2 g·kg^-1) Wuzi Yanzong Pills, and model+vitamin C (100 mg·kg^-1) groups (n=8). In addition, 8 SD male rats of 3 months old were selected as the control group. Rats in treatment groups were fed the diets containing different doses of Wuzi Yanzong Pills or vitamin C, and the control and model groups received a regular diet for 12 weeks. After 5 days of co-caging with 3-month-old female mice, the fertilization rate was recorded. An automated sperm analyzer was used to examine the sperm motility and count, and the testicular spermatogenesis was assessed by hematoxylin-eosin staining. The senescence cells in the testicular tissue was detected byβ-galactosidase staining, and miR-34a-5p expression was quantified via qPCR. The litter size was counted, and the body mass and body length were measured on days 1 and 30 to assess offspring development. For the offspring of 30 days old, their learning ability was examined via Morris water maze, and Nissl staining was employed to count hippocampal neurons. The miR-34a-5p expression in the hippocampal tissue of the offspring was determined by qPCR, and the protein levels of brain-derived neurotrophic factor (BDNF) and SIRT1 were determined by Western blot. Compared with the control group, the model group exhibited reductions in fertility rate, litter size, and sperm motility and count, as well as impaired testicular spermatogenesis (P<0.01). In addition, the model group showed increased senescence cells in testicular and epididymal tissue, accompanied by elevated miR-34a-5p expression in sperms. The 30-day-old offspring showed slow growth, reduced hippocampal neurons, up-regulated miR-34a-5p expression, and down-regulated protein levels of SIRT1 and BDNF in the hippocampus (P<0.01), along with impaired learning and memory performance (P<0.01). Compared with the model group, both high-dose Wuzi Yanzong Pills and vitamin C improved the fertilization rate, litter size, sperm motility, sperm count, and testicular spermatogenesis (P<0.05). The 30-day-old offspring in the two groups showed accelerated growth and development, increased hippocampal neurons, and elevated BDNF protein level in the hippocampus (P<0.05), along with enhanced learning and memory capabilities (P<0.05). Compared with the vitamin C group, the high-dose Wuzi Yanzong Pills group exhibited accelerated offspring growth (P<0.05), increases in fertilization rate and litter size (P<0.05), and improved learning and memory abilities (P<0.05). These findings indicate that Wuzi Yanzong Pills can improve testicular spermatogenesis and sperm quality in aged rats, thereby enhancing offspring's learning and memory performance. Specifically, Wuzi Yanzong Pills regulate miR-34a-5p expression to delay spermatogenic cell senescence in the testicular tissue and improve the offspring's cognitive function by miR-34a-5p mediated intergenerational transmission.

Key words

aged male parent / Wuzi Yanzong Pills / miR-34a-5p/SIRT1

引用本文

刘子豪, 萧闵, 江晓翠, 潘琴, 邓朝阳, 祝中意, 曹继刚. 基于miR-34a-5p/SIRT1信号通路探究SD大鼠高龄父代对子代学习能力的影响及五子衍宗丸的干预作用. 中国中药杂志, 2026 , 51 (1) : 250 -259 . DOI: 10.19540/j.cnki.cjcmm.20250916.801

Zi-hao LIU, Min XIAO, Xiao-cui JIANG, Qin PAN, Chao-yang DENG, Zhong-yi ZHU, Ji-gang CAO. Influences of aged male parents on learning ability of offspring in SD rats and intervention effect of Wuzi Yanzong Pills based on miR-34a-5p/SIRT1 signaling pathway[J]. Chinese Journal of Traditional Chinese Medicine, 2026 , 51 (1) : 250 -259 . DOI: 10.19540/j.cnki.cjcmm.20250916.801

基金

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湖北省自然科学基金项目(2023AFB990)

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2026年第51卷第1期

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文章信息

doi: 10.19540/j.cnki.cjcmm.20250916.801

接收时间：2025-08-09
首发时间：2026-06-25
出版时间：2026-01-01

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收稿日期：2025-08-09

基金

湖北省自然科学基金项目(2023AFB990)

作者信息

^1．湖北中医药大学中医学院，湖北武汉 430065

^2．湖北时珍实验室，湖北武汉 430065

^3．湖北中医药大学实验中心，湖北武汉 430065

^4．湖北中医药大学基础医学院，湖北武汉 430065

^5．湖北省妇幼保健院，湖北武汉 430070

通讯作者:

曹继刚，博士，主任医师，教授，博士生导师，主要从事中医藏象理论及其应用、中医泌尿生殖系统理论及其临床研究，E-mail: 774941339@qq.com；

萧闵，博士，副研究员，主要从事动物模型及中西医结合防治不孕不育研究，E-mail: 531637551@qq.com

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https://castjournals.cast.org.cn/joweb/zgzyzz/CN/10.19540/j.cnki.cjcmm.20250916.801

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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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