目的 探讨白芍、炙甘草及白芍-炙甘草药对的抗葡聚糖硫酸钠(dextran sulfate-sodium，DSS)诱导的溃疡性结肠炎(ulcerative colitis)的药效，以及对铁死亡的调控作用。方法 将60只C57BL/6小鼠随机分为空白对照组、模型对照组、阳性对照组、白芍给药组、炙甘草给药组以及白芍-炙甘草配伍给药组。除空白对照组外，其余各组均给予3。5％DSS造模建立结肠炎模型，并按照分组给予不同药物灌胃干预，连续给药7天，实验期间记录小鼠体重。第8天处死小鼠提取结肠组织，测量结肠长度、疾病活动指数(disease activity index，DAI)，通过苏木素-伊红(haematoxylin-eosin，HE)染色观察结肠组织病理学改变;通过透射电镜观察组织中线粒体的形态变化，生化试剂盒检测结肠组织中Fe2+、还原型谷胱甘肽(glutathione，GSH)、丙二醛(malonaldehyde，MDA)、超氧化物歧化酶(superoxide dismutase，SOD)和过氧化氢酶(catalase，CAT)的含量，蛋白免疫印迹法检测结肠组织谷胱甘肽过氧化物酶4(glutathion peroxidase，GPX4)、溶质载体家族7成员11(solute vector family 7 members 11，SLC7A11)蛋白表达水平。结果 与空白对照组比较，模型组小鼠体重降低，DAI评分升高，结肠长度明显缩短;模型组结肠组织中，线粒体膜皱缩，线粒体嵴模糊;同时，Fe2+、MDA含量增加以及GPX4、SLC7A11蛋白表达均明显降低(P＜0。05);与模型组比较，各给药组小鼠体重下降、结肠长度缩短以及DAI评分上升得到明显改善。白芍、炙甘草和白芍-炙甘草药对组Fe2+、MDA含量显著减少(P＜0。05)，GPX4、SLC7A11蛋白表达升高(P＜0。05和P＜0。01)，GSH和SOD含量显著增加(P＜0。05)，且白芍-炙甘草药对的调控作用明显强于白芍和炙甘草。结论 白芍-炙甘草药对抗溃疡性结肠炎的作用较单味药相比显著增强，且机制与其抑制溃疡性结肠炎小鼠结肠组织铁死亡水平有关。
Study on the anti-ulcerative colitis mechanism of Baishao and Zhigancao compatibility down-regulating ferroptosis
Objective Investigation of the efficacy of Paeonia lactiflora Pall.(Shaoyao),Glycyrrhiza uralensis Fisch.fried with honey(Zhigancao),and Shaoyao-Zhigancao pairs against dextran sulfate sodium(DSS)induced ulcerative colitis and the mod-ulation of ferroptosis.Methods Sixty 6-week-old male C57BL/6 mice were randomly divided into the control group,the model group,the positive control group,the Baishao group,the Zhigancao group,and the Baishao-Zhigancao combination administra-tion group.Except for the control group,all the groups were subjected to 3.5％DSS to induce ulcerative colitis,and different drugs were administered by receiving intragastric according to the groups for 7 days.The mice were sacrificed on the 8th day,and colon specimens were collected for further analysis.The disease activity index(DAI)was measured and the histopathological changes in the colon were observed by hematoxylin-eosin(HE)staining;the morphological changes of mitochondria in the tissue were observed by transmission electron microscopy,and biochemical kits were used to detect Fe2+,reduced glutathione(GSH),malonaldehyde(MDA),superoxide dismutase(SOD)and catalase(CAT)in the colon.The levels of glutathione peroxidase 4(GPX4)and solute vector family 7 member 11(SLC7 A1 1)in colon tissue were determined by Western blot.Compared with the control group,the model mice had lower body weight,higher DAI scores,and demonstrated significantly decreased colon length;the mitochondrial membrane was wrinkled and the mitochondrial cristae were blurred;both Fe2+and MDA levels increased,and the expression of GPX4 and SLC7A11 protein were significantly lower in the colon tissue of the model group(P＜0.05).Results The administration of each group resulted in body weight loss,shortened colon length,and increased DAI scores were significantly improved when compared to the model group.The levels of Fe2+and MDA were significantly reduced(P＜0.05),the expression of GPX4 and SLC7A11 proteins were increased(P＜0.05 and P＜0.01),and the levels of GSH and SOD were significantly in-creased(P＜0.05)in the groups of Baishao,Zhigancao and Baishao-Zhigancao pairs,and the modulating effect of Baishao-Zhigancao pairs was significantly stronger than that of Baishao and Zhigancao.Conclusion The effect of Baishao-Zhigancao pairs on anti-ulcerative colitis was significantly enhanced compared to a single herb,and the mechanism was related to its down-reg-ulating ferroptosis in colonic tissues of mice with ulcerative colitis.
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