医学分子生物学杂志 ›› 2025, Vol. 22 ›› Issue (1): 41-47.doi: 10.3870/j.issn.1672-8009.2025.01.007

• 论著 • 上一篇    下一篇

山柰酚调节 IL-6 / STAT3 信号通路对妊娠糖尿病大鼠炎症反应的影响 #br#

  

  1. 1承德市妇幼保健院 (承德市儿童医院) 产科 河北省承德市, 067000 2唐山市妇幼保健院妇产科 河北省唐山市, 063000
  • 出版日期:2025-01-31 发布日期:2025-02-28
  • 基金资助:
    河北省医学科学研究重点课题计划项目 (No. 20221770)

Effect of Kaempferol on Inflammatory Response in Rats with Gestational Diabetes Mellitus via Regulation of IL-6 / STAT3 Signaling Pathway #br#

  1. 1Department of Obstetrics, Chengde Maternal and Child Health Hospital (Chengde Childrens Hospital), Chengde, Hebei, 067000, China 2Department of Obstetrics and Gynecology, Tangshan Maternal and Child Health Hospital, Tangshan, Hebei, 063000, China
  • Online:2025-01-31 Published:2025-02-28

摘要: 目的 探讨山柰酚 ( kaempferol, Kpf) 调节白细胞介素-6 ( interleukin-6, IL-6) / 信号转导与转录激活子 3 (signal transducer and activator of transcription 3, STAT3) 信号通路对妊娠糖尿病 (gestational diabetes mellitus, GDM) 大鼠炎症反应的影响方法 雌雄同笼与高脂高糖喂养联合腹腔注射链脲佐菌素(streptozotocin, STZ) 构建 GDM 大鼠模型, 将造模成功大鼠按照随机数字表达分为 Model 、 Kpf 高剂量组激活剂组 (IL-6 / STAT3 通路激活剂 rIL-6), 每组 12 , 同批 12 只妊娠大鼠作为 control , 各组腹腔注射相应药物, 每天 1 , 直到妊娠 19 d。 罗氏血糖仪测量大鼠空腹血糖 ( fasting blood glucose, FBG); 分析各组大鼠妊娠结局; ELISA 法测定大鼠血清空腹胰岛素 ( fasting insulin, FINS) 及胎盘中白细胞介素 (interleukin, IL) -6、 IL-1β、 肿瘤坏死因子 ( tumor necrosis factor-α, TNF-α) 水平; 苏木精伊红(hematoxylin-eosin, HE) 染色观察大鼠胎盘组织中病理损伤; TUNEL 染色检测胎盘组织细胞凋亡; 蛋白质印迹测定胎盘中 IL-6 / STAT3 通路蛋白表达结果 control 组比较, Model 组大鼠 FBG、 FINS、 HOMAIR、 胎鼠质量、 IL-6、 IL-1β、 TNF-α 水平胎盘组织 IL-6、 p-STAT3 / STAT3 水平及细胞凋亡率增加, 活胎率窝产子数下降 (P< 0. 05); 相较于 Model , Kpf 高剂量组大鼠 FBG、 FINS、 HOMA-IR、 胎鼠质量、 IL-6、 IL-1β、 TNF-α 水平胎盘组织 IL-6、 p-STAT3 / STAT3 水平及细胞凋亡率下降, 活胎率窝产子数增加 (P< 0. 05); 相较于 Kpf 高剂量组, 激活剂组上述指标变化均显著逆转 (P< 0. 05)。 结论 Kpf可能通过抑制 IL-6 / STAT3 信号通路降低 GDM 大鼠胎盘炎症, 减轻胰岛素抵抗

关键词: 妊娠糖尿病, 山柰酚, 白细胞介素-6, 信号转导与转录激活子 3, 炎症,

Abstract: Objective To investigate the effect of kaempferol (Kpf) on inflammatory responsein rats with gestational diabetes mellitus (GDM) by regulation of the interleukin-6 (IL-6) / signaltransducer and activator of transcription 3 (STAT3) signaling pathway. Methods A rat model ofGDM was constructed by the combination of high fat and high sugar diets and intraperitoneal injection of streptozotocin ( STZ). GDM rats were then randomly divided into 5 groups: Model group, Kpf low-, medium-, and high-dose groups, and activator group ( IL-6 / STAT3 pathway activator rIL-6), with 12 rats in each group, another 12 rats without any special treatment as the control. Intraperitoneal injection of the corresponding drug was performed once a day until the 19th day of pregnancy. Roche blood glucose meter was applied to measure fasting blood glucose ( FBG) in rats. The pregnancy outcomes of rats in each group were analyzed. ELISA method was applied to determine the levels of fasting insulin (FINS) in rat serum and interleukin-6, interleukin-1β (IL-6, IL-1β), and tumor necrosis factor-α ( TNF-α) in placental tissues. Hematoxylin-eosin ( HE) staining was applied to observe pathological damage in rat placental tissues. TUNEL staining was applied to detect apoptosis in placental tissues. The expression levels of IL-6 / STAT3 pathway proteinsin placental tissues were detected by Western blotting. Results The values of FBG, FINS, HOMA-IR, fetal mouse weight, the levels of IL-6, IL-1β, TNF-α, the apoptosis rate of placental tissue cells, the expression levels of IL-6, p-STAT3 / STAT3 proteins in the Model group were increased when compared with those in the control group, while the live birth rate and the number ofoffspring were decreased when compared with those in the control group (P < 0. 05). The values ofFBG, FINS, HOMA-IR, fetal mouse mass, the levels of IL-6, IL-1β, TNF-α, the apoptosis rate of placental tissue cells, and the expression levels of IL-6, p-STAT3 / STAT3 proteins in the Kpf low-, medium-, and high-dose groups were decreased when compared with those in the Model group, while the live birth rate and the number of offspring were increased when compared withthose in the Model group (P < 0. 05). The changes of the above indicators in the activator group were reversed when compared to the Kpf high-dose group (P< 0. 05). Conclusion Kpf can alleviate placental inflammation and insulin resistance in GDM rats. Its mechanism may be related to the inhibition of IL-6 / STAT3 signaling pathway.

Key words:

gestational diabetes mellitus, kaempferol, interleukin-6, signal transduction and activator of transcription 3, inflammation, insulin resistance

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