基于铁自噬信号探究番茄红素对子宫内膜异位症大鼠炎症微环境影响的研究OA
Research of the effect of lycopene on the inflammatory microenvironment of endometriosis rats based on iron autophagy signal
目的 探讨番茄红素介导铁自噬改善子宫内膜异位症(EMs)炎症反应的潜在作用机制.方法 将50只大鼠随机分为假手术组、模型组(构建EMs模型)、低剂量实验组(造模后给予10.0 mg·kg-1的番茄红素)、高剂量实验组(造模后给予20.0 mg·kg-1的番茄红素)、阳性对照组(造模后给予1.05 mg·kg-1的米非司酮),每组10只,给药结束后检测大鼠异位子宫内膜病灶体积,试剂盒检测组织游离铁,用免疫荧光、蛋白质印迹法检测血管内皮生长因子A(VEGFA)、白细胞介素(IL)-8、核受体共激活因子4(NCOA4)、微管相关蛋白1轻链3B(LC3B)的相对表达水平.结果 假手术组、模型组、低剂量实验组、高剂量实验组、阳性对照组大鼠异位子宫内膜病灶体积分别为(0±0)、(130.92±12.45)、(97.55±10.56)、(71.96±6.46)和(54.22±2.72)mm3;游离铁水平含量分别为(262.89±23.51)、(636.97±58.75)、(523.63±46.13)、(383.30±38.92)和(603.15±69.98)μmol·kg-1;VEGFA 免疫荧光强度分别为(1 034.45±102.39)、(3 628.16±104.65)、(3 100.73±231.67)、(2 193.07±293.16)和(3 418.68±377.98)a.u.;IL-8 蛋白相对表达水平分别为 0.22±0.05、0.79±0.10、0.62±0.10、0.49±0.06 和 0.71±0.07;NCOA4 蛋白相对表达水平分别为 0.33±0.04、1.12±0.13、0.85±0.10、0.61±0.09 和1.05±0.08;LC3 Ⅱ/Ⅰ 蛋白相对表达水平分别为 0.36±0.04、1.02±0.12、0.78±0.08、0.51±0.05和0.94±0.07.模型组的上述指标分别与假手术组比较,低、高剂量实验组的上述指标分别与模型组比较,在统计学上差异均有统计学意义(均P＜0.05).结论 番茄红素显著抑制EMs大鼠炎症反应,并抑制血管生成进而缩小异位病灶体积,这可能与抑制铁自噬信号相关.
Objective To investigate the potential mechanism of lycopene mediating iron autophagy in improving the inflammatory response in endometriosis(EMs).Methods Fifty rats were randomly divided into sham group,model group(EMs model was constructed),experiment-L group(10.0 mg·kg-1 lycopene after modeled),experiment-H group(20.0 mg·kg-1 lycopene after modeled)and positive group(1.05 mg·kg-1 mifepristone after modeled),with 10 rats in each group.At the end of drug treatment,the volume of ectopic endometrial tissue were detected,and detected free iron content with a corresponding detection kit.The expressions of vascular endothelial growth factor A(VEGFA),interleukin(IL)-8,nuclear receptor coactivator 4(NCOA4)and microtubule-associated protein 1 light chain 3B(LC3B)were detected by immunofluorescence,or Western blot.Results The volumes of ectopic endometrial lesion tissues in the sham group,the model group,the experiment-L group,the experiment-H group and the positive group of rats were(0.00±0.00),(130.92±12.45),(97.55±10.56),(71.96±6.46),and(54.22±2.72)mm3,respectively;the levels of free iron were(262.89±23.51),(636.97±58.75),(523.63±46.13),(383.30±38.92)and(603.15±69.98)μmol·kg-1,respectively;the immunofluorescence intensities of VEGFA were(1 034.45±102.39),(3 628.16±104.65),(3 100.73±231.67),(2 193.07±293.16)and(3 418.68±377.98)a.u.,respectively;the relative expression levels of IL-8 protein were 0.22±0.05,0.79±0.10,0.62±0.10,0.49±0.06 and 0.71±0.07,respectively;the relative expression levels of NCOA4 protein were 0.33±0.04,1.12±0.13,0.85±0.10,0.61±0.09 and 1.05±0.08,respectively;the relative expression levels of LC3 Ⅱ/Ⅰ protein were 0.36±0.04,1.02±0.12,0.78±0.08,0.51±0.05 and 0.94±0.07,respectively.Compared the sham operation group with the model group,compared experiment-L and experiment-H groups with the model group,the differences of above indicators were all statistically significant(all P＜0.05).Conclusion Lycopene significantly inhibits inflammation and angiogenesis in EMs rats,thereby reducing the volume of ectopic lesions,which may be related to the inhibition of iron autophagy signaling.
马会;孙丽佳;马月华;舒丽莎
河北北方学院附属第一医院妇产科,河北 张家口 075000河北北方学院附属第一医院妇产科,河北 张家口 075000河北北方学院附属第一医院妇产科,河北 张家口 075000河北北方学院附属第一医院妇产科,河北 张家口 075000
医药卫生
番茄红素子宫内膜异位症炎症反应铁积累自噬
lycopeneendometriosisinflammatory responseiron accumulationautophagy
《中国临床药理学杂志》 2026 (8)
1157-1163,7
2024年政府资助临床医学优秀人才培养基金资助项目(ZF2024232)
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