SGLT-2 expression increases with glucose concentration and duration of high-glucose peritoneal dialysis solution, exacerbating peritoneal fibrosis, inflammation, and vascular lesions

Cai Qingli; Wang Kefan; He Yuanyuan; He Zhiyao; Luo Yadong; Chen Jia; Cai Mingyu

doi:10.16016/j.2097-0927.202607051

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SGLT-2 expression increases with glucose concentration and duration of high-glucose peritoneal dialysis solution, exacerbating peritoneal fibrosis, inflammation, and vascular lesions

Basic Medicine | 更新时间：2026-10-30

- SGLT-2 expression increases with glucose concentration and duration of high-glucose peritoneal dialysis solution, exacerbating peritoneal fibrosis, inflammation, and vascular lesions
- Journal of Army Medical University Vol. 48, Issue 20, Pages: 2897-2907(2026)
- 作者机构：
  
  1.陆军军医大学（第三军医大学）大坪医院：，战伤救治前沿技术研究室，重庆
  2.陆军军医大学（第三军医大学）大坪医院：，肾脏内科，重庆
- 作者简介：
  
  Cai Mingyu，E-mail：66597853@qq.com
- 基金信息：
  
  the General Joint Medical Research Project of Chongqing Municipal Science and Technology Bureau and Chongqing Municipal Health Commission(2026MSXM110)
- DOI：10.16016/j.2097-0927.202607051
  CLC： R341;R459.5;R572.02
- Received：14 July 2026，
  
  Revised：2026-09-07，
  
  Accepted：07 September 2026，
  
  Published：30 October 2026
- 稿件说明：
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蔡青利，王可樊，贺媛媛，等.SGLT-2表达随高糖腹膜透析液的浓度与时间递增而加重腹膜纤维化、炎症及血管病变［J］.陆军军医大学学报，2026，48（20）：2897-2907.DOI：10.16016/j.2097-0927.202607051.

Cai Q L，Wang K F，He Y Y，et al.SGLT-2 expression increases with glucose concentration and duration of high-glucose peritoneal dialysis solution， exacerbating peritoneal fibrosis， inflammation， and vascular lesions［J］.J Army Med Univ，2026，48（20）：2897-2907.DOI：10.16016/j.2097-0927.202607051.
蔡青利，王可樊，贺媛媛，等.SGLT-2表达随高糖腹膜透析液的浓度与时间递增而加重腹膜纤维化、炎症及血管病变［J］.陆军军医大学学报，2026，48（20）：2897-2907.DOI：10.16016/j.2097-0927.202607051. DOI：

Cai Q L，Wang K F，He Y Y，et al.SGLT-2 expression increases with glucose concentration and duration of high-glucose peritoneal dialysis solution， exacerbating peritoneal fibrosis， inflammation， and vascular lesions［J］.J Army Med Univ，2026，48（20）：2897-2907.DOI：10.16016/j.2097-0927.202607051. DOI：

摘要

目的

腹膜透析（peritoneal dialysis，PD）是终末期肾脏病的重要替代治疗方式，但长期高糖腹透液暴露可诱发腹膜纤维化、炎症及血管病变，导致超滤衰竭。钠-葡萄糖协同转运蛋白2（sodium-glucose cotransporter 2，SGLT-2）在腹膜组织中表达，可能参与高糖诱导的腹膜损伤。本研究旨在观察SGLT-2在PD患者及高糖腹透液小鼠模型腹膜组织中的表达定位与变化规律，分析其与腹膜病理损伤的定量关系，为SGLT-2作为腹膜损伤潜在生物标志物及后续干预靶点研究提供实验依据。

方法

①选取2024年12月至2025年12月于陆军军医大学大坪医院肾脏内科首次行腹膜透析置管术的终末期肾脏病患者25例，采用免疫组织化学染色和免疫荧光双染检测PD患者腹膜组织中SGLT-2的表达与定位。②选取6~8周龄SPF级C57BL/6雄性小鼠60只，体质量（22.5±1.5）g，构建7.00%葡萄糖腹透液诱导的腹膜损伤模型。取诱导1周小鼠的腹膜组织，采用免疫组织化学染色和免疫荧光双染检测SGLT-2的表达与定位。分别于第1、4、8、12周收集腹膜组织，采用HE染色评估腹膜病理损伤，免疫组织化学染色观察SGLT-2表达的时间依赖性变化。构建2.50%、4.25%和7.00%葡萄糖腹透液小鼠模型，干预12周后取材，采用HE染色评估腹膜病理损伤，免疫组织化学染色观察SGLT-2表达的浓度依赖性变化。Spearman相关分析SGLT-2表达与腹膜组织病理损伤程度（间皮下层厚度、急慢性炎症评分、血管病变评分）之间的相关性。③构建30 mmol/L 高糖刺激下人腹膜间皮细胞株（human peritoneal mesothelial cells，HPMCs）和人脐静脉内皮细胞株（human umbilical vein endothelial cells，HUVECs）模型，RT-qPCR检测SGLT-2 mRNA表达。

结果

①SGLT-2在PD患者腹膜组织中主要表达于腹膜间皮细胞和血管内皮细胞。②SGLT-2在PD小鼠腹膜组织中主要表达于腹膜间皮细胞和血管内皮细胞。7.00%高糖腹透液诱导显著上调小鼠腹膜组织SGLT-2表达，且随着诱导时间延长逐渐增加，SGLT-2表达量在12周时达到高峰，与对照组比较，8周组、12周组SGLT-2阳性细胞率均显著升高（

0.000 1），且12周组高于8周组（

=0.013 3）。随着腹透液葡萄糖浓度的升高，小鼠腹膜组织SGLT-2表达水平逐渐上调，12周时7.00%高糖腹透液小鼠的腹膜组织SGLT-2表达水平较4.25%高糖腹透液显著升高（

0.000 1）；HE染色显示腹膜间皮下层厚度、炎症及纤维化程度随浓度升高而加重。相关性分析显示，SGLT-2表达水平与间皮下层厚度（

=0.766 5，

0.000 1）、慢性炎症评分（

=0.921 0，

0.000 1）和血管病变评分（

=0.882 9，

0.000 1）均呈显著正相关，而与急性炎症评分无显著相关性（

=0.223 9，

=0.297 3）。③体外实验表明高糖刺激可显著上调HPMCs与HUVECs中SGLT-2 mRNA及蛋白表达，24 h时HPMCs、HUVECs表达达到峰值（

0.001）。

结论

高糖微环境可上调腹膜SGLT-2表达，其水平与腹膜炎症、纤维化及血管病变密切相关。SGLT-2可能参与高糖诱导的腹膜损伤过程，有望作为腹膜损伤评估的潜在生物标志物及干预靶点。

Abstract

Objective

Peritoneal dialysis (PD) is an important renal replacement therapy for end-stage renal disease

but long-term exposure to high-glucose dialysate can induce peritoneal fibrosis

inflammation

and vascular lesions

leading to ultrafiltration failure. Sodium‑glucose cotransporter 2 (SGLT‑2) is expressed in peritoneal tissues and may participate in high glucose‑induced peritoneal injury. This study aimed to investigate the expression

localization

and dynamic changes of SGLT-2 in peritoneal tissues from PD patients and a mouse model of high-glucose peritoneal dialysis solution

and to analyze the quantitative relationship between SGLT-2 expression and peritoneal pathological injury

thereby providing experimental evidence for SGLT-2 as a potential biomarker of peritoneal injury and for a subsequent intervention target.

Methods

① Twenty-five patients with end-stage renal disease who underwent peritoneal dialysis catheterization for the first time in Department of Nephrology of our hospital between December 2024 and December 2025 were enrolled. Immunohistochemistry (IHC) and immunofluorescence double staining were used to detect the expression and localization of SGLT-2 in peritoneal tissues of PD patients. ② Sixty SPF male C57BL/6 mice [6 to 8 weeks old

weighing (22.5±1.5) g] were subjected to establish a peritoneal injury model induced by 7.00% glucose peritoneal dialysis solution. Peritoneal tissues from mice after 1 week of induction were collected

and IHC and immunofluorescence double staining were employed to detect the expression and localization of SGLT-2. Peritoneal tissues were harvested at weeks 1

and 12

respectively; HE staining was performed to evaluate peritoneal pathological injury

and IHC was applied to observe time-dependent changes in SGLT-2 expression. Mouse models treated with 2.50%

4.25%

and 7.00% glucose peritoneal dialysis solutions were constructed. After 12 weeks of intervention

peritoneal tissue samples were collected; HE staining and IHC were carried out to observe peritoneal pathological injury and concentration-dependent changes in SGLT-2 expression. Spearman correlation analysis was utilized to analyze the correlation between SGLT-2 expression and the degree of peritoneal histopathological injury (submesothelial layer thickness

acute and chronic inflammation scores

and vascular lesion score). ③ Human peritoneal mesothelial cells (HPMCs) and human umbilical vein endothelial cells (HUVECs) stimulated with 30 mmol/L high glucose were established

and RT-qPCR was used to detect the mRNA expression of SGLT-2.

Results

① SGLT-2 was mainly expressed in peritoneal mesothelial cells and vascular endothelial cells in peritoneal tissues of PD patients.② SGLT-2 was mainly expressed in peritoneal mesothelial cells and vascular endothelial cells in peritoneal tissues of PD mice. Induction with 7.00% high-glucose peritoneal dialysis solution significantly upregulated SGLT-2 expression in mouse peritoneal tissues

which gradually increased with the prolongation of induction time and reached a peak at 12 weeks. Compared with the control group

the percentage of SGLT-2-positive cells was significantly increased in the 8- and 12-week groups (

0.000 1)

and was higher in the 12-week group than in the 8-week group (

=0.013 3). With the increase of glucose concentration in peritoneal dialysis solution

the expression level of SGLT-2 in mouse peritoneal tissue was gradually upregulated. At 12 weeks

SGLT-2 expression in the peritoneal tissue of mice treated with 7.00% high-glucose peritoneal dialysate was significantly higher than that in mice treated with 4.25% high-glucose peritoneal dialysate (

0.000 1). HE staining showed that the thickness of the submesothelial layer

inflammation

and fibrosis of the peritoneum aggravated with the increase of concentration. Correlation analysis revealed that the expression level of SGLT-2 was significantly positively correlated with submesothelial layer thickness (

=0.766 5

0.000 1)

chronic inflammation score (

=0.921 0

0.000 1)

and vascular lesion score (

=0.882 9

0.000 1)

but not significantly correlated with acute inflammation score (

=0.223 9

=0.297 3). ③

In vitro

experiments demonstrated that high-glucose stimulation significantly upregulated the mRNA and protein expression of SGLT-2 in HPMCs and HUVECs

with peak expression at 24 h.

Conclusion

High-glucose microenvironment upregulates the expression of peritoneal SGLT-2

and its level is closely associated with peritoneal inflammation

fibrosis

and vascular lesions. SGLT-2 may be involved in the process of high-glucose-induced peritoneal injury and is expected to serve as a potential biomarker for peritoneal injury assessment and as a therapeutic target.

关键词

Keywords

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