叶酸补充有效改善高盐饮食诱发的小鼠肾脏纤维化病理进程

doi:10.12122/j.issn.1673-4254.2026.03.24

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (3): 707-714.doi: 10.12122/j.issn.1673-4254.2026.03.24

• 基础研究 • 上一篇

叶酸补充有效改善高盐饮食诱发的小鼠肾脏纤维化病理进程

唐芳¹^,²(), 王永怡¹(), 梁婷婷¹, 何伟樱¹, 劳惠绿¹, 宋家乐¹^,³^,⁴()

^1.桂林医科大学，公共卫生学院，广西桂林 541199
^2.桂林医科大学，检验与生物技术学院，广西桂林 541199
^2.梧州医学高等专科学校，广西梧州 543199
^3.广西环境暴露组学与全生命周期健康重点实验室，广西桂林 541199

收稿日期:2025-08-16 出版日期:2026-03-20 发布日期:2026-03-26
通讯作者: 宋家乐 E-mail:3257377147@qq.com;3197299839@qq.com;songjiale@glmc.edu.cn
作者简介:唐芳，学士，E-mail: 3257377147@qq.com
王永怡，在读硕士研究生，E-mail: 3197299839@qq.com
第一联系人：本文共同第一作者。
基金资助:
中央引导地方科技发展基金专项(桂科ZY22096025);广西壮族自治区大学创新创业训练计划(202210601038);广西壮族自治区八桂青年拔尖人才培养项目(GCHH〔2024〕55)

Folic acid supplementation alleviates high-salt diet-induced renal fibrosis in mice

Fang TANG¹^,²(), Yongyi WANG¹(), Tingting LIANG¹, Weiying HE¹, Huilv LAO¹, Jiale SONG¹^,³^,⁴()

^1.School of Public Health, Guilin Medical University, Guilin 541199, China
^2.School of Laboratory Medicine and Biotechnology, Guilin Medical University, Guilin 541199, China
^2.Wuzhou Medical College, Wuzhou 543199, China
^3.Guangxi Key Laboratory of Environmental ExPosomics and Whole Life Cycle Health, Guilin 541199, China

Received:2025-08-16 Online:2026-03-20 Published:2026-03-26
Contact: Jiale SONG E-mail:3257377147@qq.com;3197299839@qq.com;songjiale@glmc.edu.cn

摘要/Abstract

摘要：

目的探讨2周叶酸对8%高盐饮食（HS）诱导肾脏纤维化的保护作用。方法将28只小鼠随机分为对照组（AIN-93G饲料）、高盐组（HS组，含8%NaCl的AIN-93G饲料）、低剂量叶酸组（LFA组，含8%NaCl的AIN-93G饲料+灌胃FA 0.56 mg·kg^-1·d^-1）和高剂量叶酸组（HFA组，含8%NaCl的AIN-93G饲料+灌胃FA 5.6 mg·kg^-1·d^-1），7只/组。记录小鼠体质量、摄食量、饮水量、尾动脉收缩压和心率变化。测定血清肌酐（SCr）和炎症因子（IL-1β、IL-6和TNF-α）水平。采用HE、PAS、Masson和天狼星红染色观察肾脏组织学变化。检测Kim1，Vimentin，αSma及Ecadherin的mRNA表达及E-cadherin、Vimentin和α-SMA的蛋白表达。结果与HS组相比，叶酸干预降低小鼠饮水量（P<0.05）。叶酸干预可降低HS组小鼠尾动脉收缩压、心率及肾脏指数与血清SCr水平（均P<0.05）。叶酸干预降低HS小鼠血清TNF-α，且降低IL-1β、IL-6水平（均P<0.05）。Masson和天狼星红染色显示，HS+LFA组的肾小球和肾间质纤维化指数均下降（P<0.05），HS+HFA组纤维化指数下降（P<0.05）。免疫组化结果显示，叶酸干预增加HS小鼠肾脏组织中E-cadherin蛋白表达并抑制Vimentin的蛋白表达（均P<0.05）。低、高剂量的叶酸均可抑制HS所诱发肾脏纤维化相关标志物（Vimentin，Kim1和αSma）的mRNA和蛋白表达（均P<0.05），减少间质纤维组织堆积，改善肾脏组织纤维化的发生。叶酸干预同时可上调Ecadherin 的mRNA表达参与缓解肾脏纤维化的发生。结论叶酸干预能够改善高盐饮食小鼠肾脏中炎症反应，延缓肾脏纤维化病变。低剂量叶酸的作用效果优于高剂量叶酸，其保护机制可能与调控Ecadherin，Kim1，Vimentin和αSma 的表达有关。

关键词: 短期高盐, 肾脏损伤, 叶酸干预, 肾脏纤维化

Abstract:

Objective To investigate the protective effect of 2-week dietary folic acid (FA) supplementation against renal fibrosis induced by high-salt (HS) diet in mice. Methods Twenty-eight mice were randomly divided into control, HS (8% NaCl) diet group, HS+low-dose FA (FA: 0.56 mg/kg) group and HS+high-dose FA (5.6 mg/kg) group. The changes in body weight, food intake, water consumption, tail artery systolic pressure, and heart rate of the mice were monitored, and serum levels of creatinine (SCr) and inflammatory cytokines (IL-1β, IL-6, and TNF-α) were measured. Renal histopathology of the mice was assessed using HE, periodic acid-Schiff (PAS), Masson, and Sirius red staining. Renal expressions of Kim1, vimentin, α-Sma, and E-cadherin mRNAs and E-cadherin, vimentin, and α‑SMA proteins were detected using RT-qPCR and immunohistochemistry. Results In mice feeding a HS diet, FA supplementation significantly reduced their water intake, lowered tail artery systolic pressure, heart rate, renal index and serum SCr levels, reducing also serum levels of TNF‑α , IL-1β, and IL-6. Masson and Sirius red staining revealed markedly reduced glomerular and interstitial fibrosis indices in HS+low-dose FA group, while the mice in HS+high-dose FA group showed mixed fibrotic improvements. Immunohistochemical results demonstrated that FA significantly upregulated E-cadherin protein expression and suppressed vimentin expression in renal tissues. Both FA doses inhibited HS-induced mRNA and protein expressions of fibrosis markers (Vimentin, Kim1 and α-Sma), attenuated interstitial collagen deposition, and alleviated renal fibrosis. FA also upregulated renal E-cadherin mRNA expression, contributing to fibrosis mitigation. Conclusion FA intervention ameliorates renal inflammation and delays fibrosis progression in HS-fed mice. Low-dose FA supplementation produces better protective effect than high-dose FA, likely mediated by regulation of renal E-cadherin, Kim1, vimentin, and α-Sma expressions.

Key words: short-term high salt, renal damage, folic acid intervention, renal fibrosis

唐芳, 王永怡, 梁婷婷, 何伟樱, 劳惠绿, 宋家乐. 叶酸补充有效改善高盐饮食诱发的小鼠肾脏纤维化病理进程[J]. 南方医科大学学报, 2026, 46(3): 707-714.

Fang TANG, Yongyi WANG, Tingting LIANG, Weiying HE, Huilv LAO, Jiale SONG. Folic acid supplementation alleviates high-salt diet-induced renal fibrosis in mice[J]. Journal of Southern Medical University, 2026, 46(3): 707-714.

图/表 8

表1 引物序列

Tab.1 Primer sequences used in this study

Gene	Forward primer (5'→3')	Revise primer (5'→3')
Ecadherin	GGGACAAAGAAACAAAGGT	TGACACGGCATGAGAATAG
Vimentin	AGCCTCTATTCCTCATCCC	TAGTTGGCAAAGCGGTCAT
αSma	AGCATCCGACCTTGCTAACG	CCAGAGTCCAGCACAATACCAG
Kim1	ATGGCACTGTGACATCCTC	CCAACATAGAAGCCCTTAG

图1 FA对高盐饮食小鼠体质量、摄食量及饮水量影响

Fig.1 Effect of folic acid (FA) supplementation on body weight, food intake and water consumption in mice fed a high-salt (HS) diet (n=7). *P<0.05, **P<0.01 vs CON, #P<0.05 vs HS.

图2 FA对高盐饮食小鼠血压和心率的影响

Fig.2 Effect of FA on blood pressure and heart rate in mice fed a HS diet (n=7). *P<0.05 vs CON, #P<0.05 vs HS.

图3 FA对高盐饮食小鼠肾脏指数和肾功能指标的影响

Fig.3 Effect of FA on kidney index and renal function parameters in mice fed a HS diet. *P<0.05 vs CON, #P<0.05, ##P<0.01 vs HS.

图4 FA对高盐饮食小鼠血清炎症因子分泌的影响

Fig.4 Effect of FA on serum levels of inflammatory cytokines in mice fed a HS diet. *P<0.05 vs CON, #P<0.05 vs HS.

图5 FA对高盐饮食小鼠肾脏组织皮质及髓质形态学(HE/PAS染色)的影响

Fig.5 Effect of FA on histopathology of the renal cortex and medulla in mice fed a HS diet (HE/PAS staining, original magnification: ×400). A: HE staining (Scale bar=50 μm). B: PAS staining (Scale bar=50 μm).

图6 FA对高盐饮食小鼠肾脏组织皮质及髓质纤维化(Masson/天狼星红染色)的影响

Fig.6 Effect of FA on histopathology of the renal cortex and medulla fibrosis in mice fed a HS diet (Masson/Sirius Red staining, ×400). A: Masson staining(Scale bar=50 μm); B: Sirius Red staining (Scale bar=50 μm). *P<0.05,**P<0.01, ***P<0.001 vs CON; #P<0.05, ##P<0.01 vs HS.

图7 FA对高盐饮食小鼠肾脏中E-cadherin、Vimentin、Kim-1和α-SMA蛋白及mRNA表达的影响

Fig.7 Effect of FA on protein and mRNA levels of E-cadherin, vimentin,Kim-1 and α-SMA in the kidneys of mice fed a HS diet (Immunohistochemical staining, ×400). A: Protein levels of E-cadherin (Scale bar=50 μm). B: Protein levels of Vimentin (Scale bar=50 μm). C: Protein and mRNA levels of vimentin, Kim-1 and α-SMA. *P<0.05, **P<0.01 vs CON; #P<0.05, ##P<0.01, ###P<0.001 vs HS.

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叶酸补充有效改善高盐饮食诱发的小鼠肾脏纤维化病理进程

Folic acid supplementation alleviates high-salt diet-induced renal fibrosis in mice

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