首页|甜橙黄酮通过抑制铁死亡途径改善溃疡性结肠炎小鼠肠道黏膜功能障碍的研究

甜橙黄酮通过抑制铁死亡途径改善溃疡性结肠炎小鼠肠道黏膜功能障碍的研究

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目的 研究甜橙黄酮通过抑制铁死亡途径对溃疡性结肠炎(UC)小鼠肠道黏膜功能障碍的影响.方法 将C57BL/6小鼠随机分为对照组、模型组、阳性组和低、中、高剂量实验组.除对照组外,其余各组建立UC模型.在造模的同时,对照组和模型组均给予灌胃等量0.9%NaCl,低、中、高剂量实验组灌胃10、20、40 mg·kg-1甜橙黄酮,阳性组给予灌胃50 mg·kg-1美沙拉嗪,每天1次,灌胃14 d.观察小鼠一般情况、结肠长度、肠质量指数、疾病活动指数(DAI)、黏膜损伤指数(CMDI)评分,以试剂盒法检测D-乳酸(D-LA)、二胺氧化酶(DAO)、白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)水平,以蛋白质印迹(Western blot)法检测紧密连接蛋白闭合蛋白(Occludin)、紧密连接蛋白-1(Claudin-1)、非糖基化的xCT(SLC7A11)、谷胱甘肽过氧化物酶4(GPX4)蛋白的表达水平.结果 对照组、模型组和低、中、高剂量实验组血清 DAO 分别为(9.23±1.28)、(34.61±3.95)、(29.36±3.34)、(23.41±2.74)和(16.75±2.57)U·mL-1,血清 D-LA 分别为(7.04±1.71)、(18.25±1.05)、(15.14±1.56)、(11.43±1.70)和(8.93±1.56)ng·mL-1,Occludin蛋白相对表达水平分别为 0.89±0.08、0.25±0.05、0.37±0.03、0.48±0.05和 0.66±0.07,Claudin-1 蛋白相对表达水平分别为 0.83±0.09、0.33±0.05、0.47±0.05、0.59±0.06 和 0.72±0.07,GPX4 蛋白相对表达水平分别为 0.85±0.06、0.23±0.05、0.36±0.04、0.53±0.06 和 0.72±0.08,SLC7A11 蛋白相对表达水平分别为 0.95±0.06、0.30±0.04、0.42±0.05、0.65±0.05和0.84±0.05.对照组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.05);模型组的上述指标与低、中、高剂量实验组比较,在统计学上差异均有统计学意义(均P<0.05).结论 甜橙黄酮可抑制铁死亡途径,进而改善UC小鼠肠道黏膜功能障碍.
Sinensetin improves intestinal mucosal dysfunction in mice with ulcerative colitis by inhibiting iron death pathway
Objective To investigate the effects of Sinensetin on intestinal mucosal dysfunction in mice with ulcerative colitis by inhibiting iron death pathway.Methods C57BL/6 mice were randomly divided into control group,model group,positive group and low,medium,high dose experimental groups.UC model was established in all groups except control group.At the same time,control group and model group were given the same amount of 0.9%NaCl by intragastric administration;low,medium and high dose experimental groups were given intragastric administration of 10,20 and 40 mg·kg-1 sinensetin;positive group was given intragastric administration of 50 mg·kg-1mesalazine,once a day,for 14 days.The general condition,colon length,intestinal weight index,disease activity index(DAI)and mucosal damage index(CMDI)scores of mice were observed.D-lactic acid content(D-LA),diamine oxidase(DAO),interleukin-1 β(IL-1 β),interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)were detected by the kit.The expression of compact connecting closure protein(Occludin),tight junction protein-1(Claudin-1),non-glycosylated xCT(SLC7A11)and glutathione peroxidase 4(GPX4)were detected by Western blot.Results The serum DAO of control group,model group and low,medium,high dose experimental groups were(9.23±1.28),(34.61±3.95),(29.36±3.34),(23.41±2.74)and(16.75±2.57)U·mL-1,respectively;serum D-LA were(7.04±1.71),(18.25±1.05),(15.14±1.56),(11.43±1.70)and(8.93±1.56)ng·mL-1,respectively;the expression of Occludin protein were 0.89±0.08,0.25±0.05,0.37±0.03,0.48±0.05 and 0.66±0.07,respectively;the expression of Claudin-1 protein were 0.83±0.09,0.33±0.05,0.47±0.05,0.59±0.06 and 0.72±0.07,respectively;GPX4 protein expression were 0.85±0.06,0.23±0.05,0.36±0.04,0.53±0.06 and 0.72±0.08,respectively;SLC7A11 protein expressions were 0.95±0.06,0.30±0.04,0.42±0.05,0.65±0.05 and 0.84±0.05,respectively.There was statistical significance between control group and model group(all P<0.05).There were significant differences in the above indexes between model group and low,medium,high dose experimental groups(all P<0.05).Conclusion Sinensetin can inhibit iron death pathway and improve intestinal mucosal dysfunction in mice with ulcerative colitis.

sinensetiniron death pathwayulcerative colitisintestinal mucosal function

余莉萍、施凉潘

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福建医科大学附属泉州市第一医院,痔疮科,福建泉州 362000

福建医科大学附属泉州市第一医院,胃肠外科,福建泉州 362000

甜橙黄酮 铁死亡途径 溃疡性结肠炎 肠道黏膜功能

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(7)
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