化合物A34对糖尿病小鼠的降糖作用及机制探讨
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国家自然科学基金(81903559);河北省自然科学基金(H2020208003);河北省自然科学基金生物医药联合基金重点项目(H2021208002);辽宁省教育厅重点攻关项目(JYTZD2023140)


Anti-diabetic effect and mechanism of compound A34 in diabetic mice
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    摘要:

    为研究一种新型可溶性环氧化物水解酶(soluble epoxide hydrolase,sEH)抑制剂(A34)对糖尿病小鼠的降糖作用,探讨其作用机制,连续5天给小鼠腹腔注射链脲佐菌素(streptozotocin,STZ,50 mg/(kg·d),诱导1型糖尿病(type 1 diabetes mellitus,T1DM)小鼠模型。通过饮水给药,考察A34对糖尿病小鼠饮水摄食量、非禁食血糖、空腹血糖、葡萄糖耐量和血浆胰岛素水平的影响,研究A34的降糖作用;通过研究胰岛中sEH表达水平、胰岛形态变化及血浆中细胞因子干扰素-γ(INF-γ)和白介素-4(IL-4)的含量,分析A34降糖的作用机制。结果表明:与模型组相比,A34有效改善了糖尿病小鼠多饮、多食症状及葡萄糖耐量情况(p<0.01),降低了空腹血糖和非禁食血糖(p<0.01),提高了血浆胰岛素水平(p<0.05);小鼠胰岛中sEH表达量降低(p<0.01),胰岛受损减轻,血浆中IFN-γ与IL-4含量比值降低(p<0.05)。A34可能通过调控促炎和抗炎细胞因子的动态平衡,保护胰岛β细胞免受损伤,从而改善小鼠胰岛β细胞功能,发挥降糖作用。

    Abstract:

    In order to detemine the anti-diabetic effect and potential mechanism of a novel soluble epoxide hydrolas inhibitor (A34) on diabetic mice. Type 1 diabetes mellitus (T1DM) mice were induced by streptozotocin (50 mg/(kg·d) for 5 days, ip.)and the hypoglycemic effect of A34 were evaluated by water and food intake, non-fasting and fasting blood glucose, glucose tolerance and plasma insulin level in diabetic mice after water administration.The underlying mechanism was explored via measuring the expression level of sEH in islets, the morphological change of islets and the concerntration of cytokines INF-γ and IL-4 in plasma. Compared with diabetic model group, the water and food intake(p<0.01, p<0.05), blood glucose (p<0.01), glucose tolerance (p<0.01) and plasma insulin level (p<0.05 ) were improved in A34 group. Additionally, A34 could protect pancreatic islet morphology, suppress sEH expression in islet (p<0.01), reduce the ratio of INF-γ to IL-4 in plasma(p<0.05 ). These results showed that A34 prevents hyperglycemia and β-cell dysfunction through regulating the dynamic balance of pro-inflammatory and anti-inflammatory cytokines in diabetic mice.

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孙艳平,张雪玉,田 野,陈 猛,窦珊珊,李 硕,张慧敏,宋慧佳,赵燕芳,高子彬.化合物A34对糖尿病小鼠的降糖作用及机制探讨[J].河北科技大学学报,2024,45(5):479-486

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  • 收稿日期:2024-01-09
  • 最后修改日期:2024-04-08
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  • 在线发布日期: 2024-11-01
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