岩藻黄质调节Notch/Snail1信号通路对妊娠期糖尿病大鼠胰岛素抵抗的影响

doi:10.3969/j.issn.1006-6233.2025.12.014

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摘要 目的: 探讨岩藻黄质(FUC)调节Notch/锌指蛋白转录因子1(Snail1)信号通路对妊娠期糖尿病(GDM)大鼠胰岛素抵抗的影响。方法: 构建GDM大鼠模型,将建模成功的大鼠分为GDM组、L-FUC、M-FUC、H-FUC(灌胃13、26、65mg/kg的FUC)、H-FUC+VPA组(灌胃65mg/kg的FUC+腹腔注射300mg/kg的Notch激活剂VPA),每组各10只。另取10只正常孕鼠为Ctrl组,Ctrl组与GDM组给予等量由10%DMSO、40%PEG300、5%吐温80、45%生理盐水配制的混合液,1次/d,连续2周。血糖仪检测大鼠FBG、FINS水平,计算IRI;试剂盒检测大鼠TG、TC水平;HE染色观察大鼠肝组织形态变化;ELISA检测大鼠血清TNF-α、IL-6水平;Western blot检测大鼠肝组织中Notch/Snail1信号通路蛋白表达变化。结果: GDM组大鼠较Ctrl组肝组织细胞空泡样坏死且伴有大量炎性细胞浸润;L-FUC组、M-FUC组、H-FUC组大鼠较GDM组肝组织细胞空泡现象减少,炎症细胞浸润降低;H-FUC+VPA组大鼠较H-FUC组肝组织病理损伤加重,炎性细胞浸润增加。GDM组大鼠FBG、FINS、IRI、TC、TG、TNF-α、IL-6水平、肝组织中Notch、Snail1蛋白表达水平较Ctrl组升高(P<0.05);L-FUC组、M-FUC组、H-FUC组大鼠FBG、FINS、IRI、TC、TG、TNF-α、IL-6水平、肝组织中Notch、Snail1蛋白表达水平水平较GDM组降低且具有剂量依赖性(P<0.05);H-FUC+VPA组大鼠FBG、FINS、IRI、TC、TG、TNF-α、IL-6水平、肝组织中Notch、Snail1蛋白表达水平较H-FUC组升高(P<0.05)。结论: FUC可改善GDM大鼠胰岛素抵抗,这可能主要基于Notch/Snail1信号通路的抑制效应。

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	高丹丹
	姜海英
	李娟

关键词 ：妊娠期糖尿病, 岩藻黄质, Notch/锌指蛋白转录因子1信号通路, 胰岛素抵抗

Abstract：Objective: To explore the effect of fucoxanthin (FUC) on insulin resistance in gestational diabetes mellitus rats by regulating Notch/zinc finger transcription factor 1 (Snail1) signaling pathway. Methods: A GDM rat model was constructed, and successfully modeled rats were grouped into GDM group, L-FUC, M-FUC, H-FUC groups (gavage of 13, 26, and 65 mg/kg FUC), and H-FUC+VPA group (gavage of 65 mg/kg FUC+intraperitoneal injection of 300 mg/kg Notch activator VPA), with 10 rats in each group. Another 10 normal pregnant mice served as the control group. The control group and the GDM group were administered the same volume of a mixture prepared with 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline once a day for 2 consecutive weeks. A blood glucose meter was used to detect the FBG and FINS in rats, and the IRI was calculated. The reagent kits were used to detect TG and TC in rats. HE staining was used to observe the morphological changes in rat liver tissue. ELISA was used to detect serum TNF-α and IL-6 in rats. Western blot was used to detect changes in Notch/Snail1 signaling pathway proteins in rat liver tissue.Results: For the control group, the GDM group showed vacuolar necrosis of liver tissue cells, accompanied by a large amount of inflammatory cell infiltration. For the GDM group, the L-FUC group, M-FUC group, and H-FUC group showed a decrease in vacuolar phenomenon and infiltration of inflammatory cells in liver tissue cells. The H-FUC+VPA group showed more severe liver tissue pathological damage and increased inflammatory cell infiltration than the H-FUC group. The GDM group showed higher FBG, FINS, IRI, TC, TG, TNF-α, IL-6, and liver tissue Notch and Snail1 proteins than the control group (P<0.05). The L-FUC group, M-FUC group, and H-FUC group showed decreased FBG, FINS, IRI, TC, TG, TNF-α, IL-6, and liver tissue Notch and Snail1 proteins than the GDM group, in a dose-dependent manner (P<0.05). The H-FUC+VPA group showed higher FBG, FINS, IRI, TC, TG, TNF-α, IL-6, and liver tissue Notch and Snail1 proteins than the H-FUC group (P<0.05). Conclusion: FUC can improve insulin resistance in GDM rats, which may be mainly based on the inhibitory effect of the Notch/Snail1 signaling pathway.

Key words： Gestational diabetes mellitus Fucoxanthin Notch/zinc finger transcription factor 1 signaling pathway Insulin resistance

基金资助:河北省卫生健康委项目,(编号:NO:20251191)

引用本文:

高丹丹, 姜海英, 李娟. 岩藻黄质调节Notch/Snail1信号通路对妊娠期糖尿病大鼠胰岛素抵抗的影响[J]. 河北医学, 2025, 31(12): 2027-2032.
GAO Dandan, JIANG Haiying, LI Juan. Effect of Fucoxanthin on Insulin Resistance in Gestational Diabetes Mellitus Rats by Regulating Notch/Snail1 Signaling Pathway. HeBei Med, 2025, 31(12): 2027-2032.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.12.014 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I12/2027

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