中国临床药理学杂志

雌马酚通过CCDC92调控AMPK/mTOR通路对糖尿病肾病足细胞损伤的作用及机制研究

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李霜青 , 刘艳 , 周韩菁

中国临床药理学杂志 | 临床与基础桥接研究 2026,42(1): 47-52

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中国临床药理学杂志 |临床与基础桥接研究 2026 , 42 (1) : 47 -52

雌马酚通过CCDC92调控AMPK/mTOR通路对糖尿病肾病足细胞损伤的作用及机制研究

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李霜青, 刘艳, 周韩菁

作者信息

浙江省金华市中心医院肾内科，浙江金华 321000

通讯作者:

李霜青 MP: 13735761966 E-mail: 13735761966@163.com

作者简介:

李霜青（1976-），女，副主任医师，主要从事糖尿病肾病方面的工作和研究

Research on the effects and mechanism of equol regulating AMPK/mTOR pathway by CCDC92 in podocyte injury of diabetic nephropathy

Shuang-qing LI, Yan LIU, Han-jing ZHOU

Affiliations

Department of Nephrology, Jinhua Municipal Central Hospital, Jinhua 321000, Zhejiang Province, China

出版时间: 2026-01-17 doi: 10.13699/j.cnki.1001-6821.2026.01.008

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摘要

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目的

研究雌马酚（equol）通过含卷曲螺旋结构域92（CCDC92）调控腺苷酸活化蛋白激酶（AMPK）/哺乳动物雷帕霉素靶蛋白（mTOR）通路对糖尿病肾病（DN）足细胞损伤的作用及其机制。

方法

将小鼠MPC5细胞分为对照组（不做任何处理），模型组（30 mmol·L^-1葡萄糖处理48 h），实验组（在模型组基础上，1 μmol·L^-1 Equol处理24 h），AAV-NC组（在实验组基础上，转染AAV-NC）和AAV-CCDC92组（在实验组基础上，转染AAV-CCDC92）。用噻唑蓝实验法检测细胞存活率，用实时荧光定量聚合酶链反应法检测CCDC92 mRNA水平，用Transwell实验法检测细胞侵袭能力，用免疫荧光实验法检测足细胞分化因子（Podocin）和肾病蛋白（Nephrin）的蛋白表达水平，用蛋白免疫印迹法检测微管相关蛋白1轻链3Ⅱ型/Ⅰ型（LC3Ⅱ/Ⅰ）、苄氯素1（Beclin-1）、AMPK和mTOR相关蛋白表达。

结果

对照组组、模型组和实验组的细胞存活率分别为（100.00±2.84）%、（64.91±9.57）%和（81.36±13.19）%。对照组、模型组、实验组、AAV-NC组和AAV-CCDC92组的CDC92 mRNA相对表达水平分别为1.00±0.12、2.26±0.35、1.42±0.19、1.48±0.22和2.05±0.34，细胞侵袭个数分别为（79.35±11.62）、（25.81±4.06）、（53.69±7.95）、（60.46±10.58）和（41.13±7.27）个，Nephrin蛋白相对表达水平分别为1.00±0.14、0.31±0.05、0.65±0.09、0.58±0.08和0.39±0.06，Podocin蛋白相对表达水平分别为1.00±0.17、0.28±0.04、0.61±0.11、0.56±0.09和0.32±0.06，LC3Ⅱ/Ⅰ蛋白相对表达水平分别为1.00±0.17、0.26±0.04、0.74±0.12、0.69±0.11和0.41±0.08，Beclin1蛋白相对表达水平分别为1.00±0.15、0.32±0.06、0.68±0.10、0.75±0.12和0.46±0.07，磷酸化（p）-AMPK/AMP相对表达水平分别为1.00±0.19、0.23±0.04、0.86±0.17、0.89±0.16和0.38±0.07，p-mTOR/mTOR相对表达水平分别为1.00±0.16、3.16±0.53、1.72±0.31、1.65±0.29和2.91±0.52。模型组的上述指标与对照组相比，实验组与模型组相比，AAV-CCDC92组与AAV-NC组相比，在统计学上差异均有统计学意义（P<0.05，P<0.01，P<0.001）。

结论

雌马酚可以通过CCDC92减轻DN足细胞损伤，该作用可能与调控AMPK/mTOR通路，提高自噬水平有关。

关键词

雌马酚 / 糖尿病肾病 / 含卷曲螺旋结构域92 / 足细胞损伤 / 自噬

Abstract

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Objective

To investigate the effects and mechanism of equol on podocyte injury in diabetic nephropathy (DN) by regulating the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway by coiled-coil domain containing 92 (CCDC92).

Methods

Mouse MPC5 cells were divided into five groups: the control group (without any treatment), the model group (treated with 30 mmol·L^-1 glucose for 48 h), the experimental group (treated with 1 μmol·L^-1 equol for 24 h on the basis of the model group), the AAV-NC group (transfected with AAV-NC on the basis of the experimental group) and the AAV-CCDC92 group (transfected with AAV-CCDC92 on the basis of the experimental group). Cell viability was detected by the methyl thiazolyl tetrazolium assay. The mRNA level of CCDC92 was determined by real-time fluorescence quantitative polymerase chain reaction. Cell invasive ability was assessed by the transwell assay. The protein relative expression levels of Podocin and Nephrin were detected by immunofluorescence assay. The protein relative expression levels of microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ (LC3Ⅱ/Ⅰ), Beclin-1, AMPK and mTOR related proteins were measured by Western blot.

Results

The cell viability rates of the control group, model group and experimental group were (100.00±2.84)%, (64.91±9.57)% and (81.36±13.19)%, respectively; the relative expression levels of CCDC92 mRNA in the control group, model group, experimental group, AAV-NC group and AAV-CCDC92 group were 1.00±0.12, 2.26±0.35, 1.42±0.19, 1.48±0.22 and 2.05±0.34, respectively; the number of invasive cells were (79.35±11.62), (25.81±4.06), (53.69±7.95), (60.46±10.58) and (41.13±7.27) cells, respectively; the relative expression levels of Nephrin protein were 1.00±0.14, 0.31±0.05, 0.65±0.09, 0.58±0.08 and 0.39±0.06, respectively; the relative expression levels of Podocin protein were 1.00±0.17, 0.28±0.04, 0.61±0.11, 0.56±0.09 and 0.32±0.06, respectively; the relative expression levels of LC3Ⅱ/Ⅰ protein were 1.00±0.17, 0.26±0.04, 0.74±0.12, 0.69±0.11 and 0.41±0.08, respectively; the relative expression levels of Beclin1 protein were 1.00±0.15, 0.32±0.06, 0.68±0.10, 0.75±0.12 and 0.46±0.07, respectively; the relative expression levels of phosphorylated (p)-AMPK/AMPK protein were 1.00±0.19, 0.23±0.04, 0.86±0.17, 0.89±0.16 and 0.38±0.07, respectively; the relative expression levels of p-mTOR/mTOR protein were 1.00±0.16, 3.16±0.53, 1.72±0.31, 1.65±0.29 and 2.91±0.52, respectively. There were statistically significant differences in the above indicators between the model group and the control group, between the experimental group and the model group and between the AAV-CCDC92 group and the AAV-NC group (P<0.05, P<0.01, P<0.001).

Conclusion

Equol can alleviate podocyte injury in DN through CCDC92, and the effects may be related to regulating the AMPK/mTOR pathway and improving autophagy level.

Key words

equol / diabetic nephropathy / coiled-coil domain containing 92 / podocyte injury / autophagy

引用本文

李霜青, 刘艳, 周韩菁. 雌马酚通过CCDC92调控AMPK/mTOR通路对糖尿病肾病足细胞损伤的作用及机制研究. 中国临床药理学杂志, 2026 , 42 (1) : 47 -52 . DOI: 10.13699/j.cnki.1001-6821.2026.01.008

Shuang-qing LI, Yan LIU, Han-jing ZHOU. Research on the effects and mechanism of equol regulating AMPK/mTOR pathway by CCDC92 in podocyte injury of diabetic nephropathy[J]. Chinese Journal of Clinical Pharmacology, 2026 , 42 (1) : 47 -52 . DOI: 10.13699/j.cnki.1001-6821.2026.01.008

基金

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金华市科技计划基金资助项目(2024-3-064)

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2026年第42卷第1期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2026.01.008

接收时间：2025-09-22
首发时间：2026-08-06
出版时间：2026-01-17

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收稿日期：2025-09-22

基金

金华市科技计划基金资助项目(2024-3-064)

作者信息

浙江省金华市中心医院肾内科，浙江金华 321000

通讯作者:

李霜青 MP: 13735761966 E-mail: 13735761966@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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