水分散橙皮素对内毒素诱导的大鼠葡萄膜炎的抗炎作用涉及核因子κB和Wnt/β-catenin信号通路。

IF 1.1 4区农林科学 Q3 VETERINARY SCIENCES

Journal of Veterinary Medical Science Pub Date : 2025-02-15 Epub Date: 2025-01-16 DOI:10.1292/jvms.24-0453

Daiki Okada, Kazutaka Kanai, Yuya Otaka, Tsubasa Matsumoto, Akane Izumoto, Yumiko Uchiyama, Noriaki Nagai, Yohei Yamashita, Yoichiro Ichikawa, Misaki Sugiuchi, Kazuki Tajima

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引用次数: 0

摘要

本研究探讨了水分散橙皮素（WD-Hpt）对内毒素性葡萄膜炎（EIU）大鼠模型的抗炎作用。大鼠在注射200 μg的脂多糖（LPS）后立即口服10、25或50 mg/kg WD-Hpt。评估临床评分、细胞炎症、房水（ApH）蛋白浓度、肿瘤坏死因子(TNF)-α、环氧化酶(COX)-2、诱导NO合成酶（iNOS）水平及组织病理学分级。免疫组织染色和mRNA分析检测TNF-α、COX-2、iNOS、活化核因子(NF)-κB p65、IκB (IκB)-α降解、磷酸化(p)-IκB激酶(IKK) α/β、β-catenin和糖原合成酶激酶(GSK)-3β的表达。与LPS治疗组（LPS txg）相比，WD-Hpt治疗组（WD-Hpt txg）临床评分提高[LPS txg；3.90±0.20,WD-Hpt txg；2.40±0.37 (p

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Anti-inflammatory effects of water-dispersible hesperetin on endotoxin-induced uveitis in rats involving the nuclear factor κB and Wnt/β-catenin signaling pathways.

This study investigated the anti-inflammatory effects of water-dispersible hesperetin (WD-Hpt) in an endotoxin-induced uveitis (EIU) rat model. The rats were orally administered 10, 25, or 50 mg/kg WD-Hpt immediately after lipopolysaccharide (LPS) injection at the concentration of 200 μg. Clinical scores, cellular inflammation, the aqueous humor (ApH) protein concentration, as well as the levels of tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) in AqH, and histopathological grades were assessed. Immunohistostaining and mRNA analyses measured expressions of TNF-α, COX-2, iNOS, activated nuclear factor (NF)-κB p65, I kappa B (IκB)-α degradation, phosphorylated (p)-IκB kinase (IKK) α/β, β-catenin, and glycogen synthase kinase (GSK)-3β. Compared to LPS treated group (LPS txg), WD-Hpt treatment groups (WD-Hpt txg) resulted in the following results: 1) clinical scores improved [LPS txg; 3.90 ± 0.20, WD-Hpt txg; 2.40 ± 0.37 (P<0.05)], 2) the number of inflammatory cells in AqH decreased [LPS txg; 8.65 ± 1.41 × 105 cells/mL, WD-Hpt txg; 3.83 ± 1.20 × 105 cells/mL (P<0.05)], 3) AqH protein concentration reduced [LPS txg; 36.65 ± 2.71 mg/mL, WD-Hpt txg; 28.73 ± 2.36 mg/mL (P<0.05)], and 4) decreased levels of TNF-α [LPS txg; 69.55 ± 7.38 pg/mL, WD-Hpt txg; 35.18 ± 9.22 pg/mL (P<0.001)], iNOS [LPS txg; 153.37 ± 12.72 μM, WD-Hpt txg; 110.79 ± 13.27 μM (P<0.05)], and COX-2 [LPS txg; 1,080.56 ± 196.06 pg/mL, WD-Hpt txg; 477.80 ± 66.61 pg/mL (P<0.01)] in AqH were observed, and histopathological grades improved [LPS txg; 2.80 ± 0.40, WD-Hpt txg; 1.50 ± 0.50 (P<0.05)]. Immunostaining and mRNA analysis revealed that 50 mg/kg WD-Hpt effectively suppressed iNOS, COX-2, NF-κB p65, IκB-α degradation, p-IKKα/β, β-catenin, and GSK-3β expression. These findings suggested that WD-Hpt exerts anti-inflammatory effects by targeting the NF-κB and Wnt/β-catenin pathways.

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来源期刊

Journal of Veterinary Medical Science 农林科学-兽医学

CiteScore

2.30

自引率

8.30%

发文量

230

审稿时长

9-18 weeks

期刊介绍： JVMS is a peer-reviewed journal and publishes a variety of papers on veterinary science from basic research to applied science and clinical research. JVMS is published monthly and consists of twelve issues per year. Papers are from the areas of anatomy, physiology, pharmacology, toxicology, pathology, immunology, microbiology, virology, parasitology, internal medicine, surgery, clinical pathology, theriogenology, avian disease, public health, ethology, and laboratory animal science. Although JVMS has played a role in publishing the scientific achievements of Japanese researchers and clinicians for many years, it now also accepts papers submitted from all over the world.