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益肾通络方通过调节链脲佐菌素诱导的糖尿病肾病小鼠的炎症和凋亡来改善肾损伤。

Yishen Tongluo formula ameliorates kidney injury modulating inflammation and apoptosis in streptozotocin-induced diabetic kidney disease mice.

作者信息

Jiayao Yuan, Suhui W U, Yufan Meng, Hanbing L I, Genlin L I, Jiangyan X U

机构信息

Clinical Pharmacology Teaching and Research Office, School of Medicine, Henan University of Chinese Medicine, Zhengzhou 450000, China.

School of Pharmacolog, Henan Medical College, Zhengzhou 450000, China.

出版信息

J Tradit Chin Med. 2025 Apr;45(2):254-265. doi: 10.19852/j.cnki.jtcm.2025.02.007.

Abstract

OBJECTIVE

To investigate the effect and mechanism of Yishen Tongluo formula (, YSTLF) in streptozotocin-induced diabetic kidney disease mice (DKD) mice.

METHODS

Thirty Institute of Cancer Research mice (specific pathogen free, SPF grade) were divided into five groups ( = 6 per group): control, DKD model, DKD model with YSTLF (4.9 g/kg), DKD model with YSTLF (9.8 g/kg), and DKD model with captopril. DKD was induced through a single intraperitoneal injection of streptozotocin (150 mg/kg). Body weight, fasting blood glucose and urine C-peptide levels were measured to assess metabolic regulation by YSTLF. Renal function was evaluated using indicators of glomerular and tubular health. Liver function was assessed by measuring aspartate aminotransferase and alanine aminotransferase levels. Renal pathological changes were examined using hematoxylin/eosin staining and transmission electron microscopy. Inflammatory and apoptosis-related factors were analyzed through enzyme-linked immunosorbent assay, immunohistochemistry, and Western blot analysis.

RESULTS

In DKD mice, fasting blood glucose, C-peptide, 24-hour urine protein (UP) levels, and renal damage were elevated, accompanied by increased inflammation and apoptosis. YSTLF significantly reduced 24-hour UP and C-peptide levels and improved kidney and liver function in DKD mice. YSTLF also mitigated glomerular hypertrophy, basement membrane thickening, and podocyte foot process effacement. It upregulated the expression of the podocyte marker podocalyxin. Furthermore, YSTLF alleviated inflammation and apoptosis, likely by reducing the overexpression of monocyte chemoattractant protein (MCP-1), Bax, and Caspase-3 in the kidneys of DKD mice.

CONCLUSIONS

These findings suggest that YSTLF ameliorates kidney injury by modulating the expression of inflammatory cytokine MCP-1 and the Bax/Caspase-3 apoptosis pathway, providing a potential therapeutic approach for DKD.

摘要

目的

探讨益肾通络方(YSTLF)对链脲佐菌素诱导的糖尿病肾病(DKD)小鼠的作用及机制。

方法

将30只癌症研究所小鼠(无特定病原体,SPF级)分为五组(每组n = 6):对照组、DKD模型组、YSTLF(4.9 g/kg)DKD模型组、YSTLF(9.8 g/kg)DKD模型组和卡托普利DKD模型组。通过单次腹腔注射链脲佐菌素(150 mg/kg)诱导DKD。测量体重、空腹血糖和尿C肽水平,以评估YSTLF对代谢的调节作用。使用肾小球和肾小管健康指标评估肾功能。通过测量天冬氨酸转氨酶和丙氨酸转氨酶水平评估肝功能。采用苏木精/伊红染色和透射电子显微镜检查肾脏病理变化。通过酶联免疫吸附测定、免疫组织化学和蛋白质免疫印迹分析炎症和凋亡相关因子。

结果

在DKD小鼠中,空腹血糖、C肽、24小时尿蛋白(UP)水平和肾损伤升高,同时炎症和凋亡增加。YSTLF显著降低DKD小鼠的24小时UP和C肽水平,并改善其肾脏和肝功能。YSTLF还减轻了肾小球肥大、基底膜增厚和足细胞足突消失。它上调了足细胞标志物足细胞外被蛋白的表达。此外,YSTLF可能通过降低DKD小鼠肾脏中单核细胞趋化蛋白(MCP-1)、Bax和半胱天冬酶-3的过表达来减轻炎症和凋亡。

结论

这些发现表明,YSTLF通过调节炎性细胞因子MCP-1的表达和Bax/半胱天冬酶-3凋亡途径改善肾损伤,为DKD提供了一种潜在的治疗方法。

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C-peptide in diabetes: A player in a dual hormone disorder?糖尿病中的 C 肽:双重激素紊乱中的一员?
J Cell Physiol. 2024 May;239(5):e31212. doi: 10.1002/jcp.31212. Epub 2024 Feb 3.
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Crosstalk between the liver and kidney in diabetic nephropathy.肝与肾在糖尿病肾病中的对话。
Eur J Pharmacol. 2022 Sep 15;931:175219. doi: 10.1016/j.ejphar.2022.175219. Epub 2022 Aug 18.

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