High-dose sinomenine attenuates ischemia/reperfusion-induced hepatic inflammation and oxidative stress in rats with diabetes mellitus

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease Pub Date : 2024-06-18 DOI:10.1002/iid3.1271

Bo Hui, Xiaogang Zhang, Dinghui Dong, Yantao Shu, Ren Li, Zhengan Yang

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Abstract

Introduction

Ischemia-reperfusion (I/R) injury, resulting from blood flow interruption and its subsequent restoration, is a prevalent complication in liver surgery. The liver, as a crucial organ for carbohydrate and lipid metabolism, exhibits decreased tolerance to hepatic I/R in patients with diabetes mellitus (DM), resulting in a significant increase in hepatic dysfunction following surgery. This may be attributed to elevated oxidative stress and inflammation. Our prior research established sinomenine's (SIN) protective role against hepatic I/R injury. Nevertheless, the impact of SIN on hepatic I/R injury in DM rats remains unexplored.

Objective and Methods

This study aimed to investigate the therapeutic potential of SIN in hepatic I/R injury in DM rats and elucidate its mechanism. Diabetic and hepatic I/R injury models were established in rats through high-fat/sugar diet, streptozotocin injection, and hepatic blood flow occlusion. Liver function, oxidative stress, inflammatory reaction, histopathology, and Nrf-2/HO-1 signaling pathway were evaluated by using UV spectrophotometry, biochemical assays, enzyme-linked immunosorbent assay, hematoxylin-eosin staining, and Western blot analysis.

Results

High-dose SIN (300 mg/kg) significantly attenuated hepatic I/R injury in DM rats, reducing serum activities of ALT and AST, decreasing the AST/ALT ratio, enhancing tissue contents of SOD and GSH-Px, suppressing the levels of TNF-α and IL-6, improving the liver histopathology, and activating Nrf-2/HO-1 signaling by promoting Nrf-2 trans-location from cytoplasm to nucleus. Low-dose SIN (100 mg/kg) was ineffective.

Conclusions

This study demonstrates that high-dose sinomenine's mitigates hepatic I/R-induced inflammation and oxidative stress in diabetes mellitus (DM) rats via Nrf-2/HO-1 activation, suggesting its potential as a preventive strategy for hepatic I/R injury in DM patients.

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大剂量西诺明可减轻糖尿病大鼠缺血/再灌注引起的肝脏炎症和氧化应激反应

导言：缺血再灌注（I/R）损伤是肝脏手术中常见的并发症，由血流中断和随后的血流恢复造成。肝脏是碳水化合物和脂质代谢的重要器官，糖尿病（DM）患者对肝脏缺血再灌注损伤的耐受性降低，导致术后肝功能异常显著增加。这可能归因于氧化应激和炎症的升高。我们之前的研究证实了西诺明（SIN）对肝脏 I/R 损伤的保护作用。然而，SIN 对 DM 大鼠肝 I/R 损伤的影响仍有待探索：本研究旨在探讨 SIN 对 DM 大鼠肝 I/R 损伤的治疗潜力，并阐明其作用机制。通过高脂/高糖饮食、链脲佐菌素注射和肝血流闭塞建立糖尿病大鼠肝I/R损伤模型。采用紫外分光光度法、生化检测法、酶联免疫吸附法、苏木精-伊红染色法和 Western 印迹分析法对肝功能、氧化应激、炎症反应、组织病理学和 Nrf-2/HO-1 信号通路进行了评估：结果：大剂量 SIN（300 mg/kg）能明显减轻 DM 大鼠肝 I/R 损伤，降低血清 ALT 和 AST 活性，降低 AST/ALT 比值，提高组织 SOD 和 GSH-Px 含量，抑制 TNF-α 和 IL-6 水平，改善肝组织病理学，并通过促进 Nrf-2 从细胞质转位到细胞核激活 Nrf-2/HO-1 信号转导。小剂量 SIN（100 毫克/千克）无效：本研究表明，大剂量西诺明能通过激活 Nrf-2/HO-1 减轻糖尿病（DM）大鼠肝脏 I/R 引起的炎症和氧化应激，这表明西诺明有可能成为 DM 患者肝脏 I/R 损伤的一种预防策略。

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来源期刊

Immunity, Inflammation and Disease Medicine-Immunology and Allergy

CiteScore

3.60

自引率

0.00%

发文量

146

审稿时长

8 weeks

期刊介绍： Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including: • cellular and molecular immunology • clinical immunology • allergy • immunochemistry • immunogenetics • immune signalling • immune development • imaging • mathematical modelling • autoimmunity • transplantation immunology • cancer immunology