基于Nrf2/HO-1通路探讨清化肠饮调控肠上皮细胞铁死亡缓解溃疡性结肠炎大鼠的机制研究  

Study on the Mechanism of Qinghuachang Yin in Alleviating Ulcerative Colitis by Regulating Ferroptosis of Intestinal Epithelial Cells Based on Nrf2/HO-1 Pathway

作　　者：张歆 朱晓勤 方文怡[4] 陈锦团[5] 赵培琳[4] ZHANG Xin;ZHU Xiaoqin;FANG Wenyi;CHEN Jintuan;ZHAO Peilin(Clinical Skills Teaching Center,Fujian University of Traditional Chinese medicine,Fuzhou,Fujian 350122,China;Academy of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou,Fujian 350122,China;Fujian Key Laboratory of Integrative Medicine on Geriatrics,Fuzhou,Fujian 350122,China;The Second Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine,Fuzhou,Fujian 350003,China;College of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou,Fujian 350122,China)

机构地区：[1]福建中医药大学临床技能教学中心,福建福州350122 [2]福建中医药大学中西医结合研究院,福建福州350122 [3]福建省中西医结合老年性疾病重点实验室,福建福州350122 [4]福建中医药大学附属第二人民医院,福建福州350003 [5]福建中医药大学中西医结合学院,福建福州350122

出　　处：《福建中医药》2023年第5期20-24,共5页Fujian Journal of Traditional Chinese Medicine

基　　金：福建省自然科学基金项目(2019J01365)。

摘　　要：目的探讨清化肠饮对溃疡性结肠炎(UC)大鼠的治疗效果及其作用机制。方法采用TNBS-乙醇法建立UC大鼠模型,将SD大鼠随机分为正常组、模型组、美沙拉嗪组、清化肠饮低剂量组(简称低剂量组)、清化肠饮中剂量组(简称中剂量组)、清化肠饮高剂量组(简称高剂量组)。造模后第3天开始予相应药液进行干预,每日1次,连续给药14 d。HE染色法观察大鼠结肠组织病理变化;测定血清中过氧化氢酶(CAT)、谷胱甘肽过氧化物酶4(GSH-px4)、铁离子、髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)、过氧化脂质(LPO)的含量;Western blot检测结肠组织中NADPH醌氧化还原酶1(NQO-1)、血红素加氧酶-1(HO-1)及核因子E2相关因子2(Nrf2)蛋白的变化。结果与正常组比较,模型组大鼠均出现相应组织病理损伤,血清CAT、GSH-px4、SOD水平及结肠组织中HO-1、NQO-1、Nrf2蛋白表达均明显降低(P<0.05),血清铁离子、MPO、LPO水平均明显升高(P<0.05);与模型组比较,美沙拉嗪组及高剂量组大鼠结肠炎的组织病理损伤明显改善,血清CAT、GSH-px4、SOD水平及结肠组织中HO-1、NQO-1、Nrf2蛋白表达均明显升高(P<0.05),铁离子、MPO、LPO水平均明显降低(P<0.05)。结论清化肠饮对溃疡性结肠炎大鼠治疗作用明显,其作用机制可能与Nrf2/HO-1通路抑制氧化应激作用和调控肠上皮细胞铁死亡来缓解溃疡性结肠炎有关。Objective:To investigate the therapeutic effect of Qinghuachang Yin on rats with ulcerative colitis(UC)and its possible mechanism.Methods:The UC rat model was established using the TNBS ethanol method.SD rats were randomly divided into normal group,model group,mesalazine group,low-dose Qinghuachang Yin group(referred to as the low-dose group),medium dose Qinghuachang Yin group(referred to as the medium-dose group)and high-dose Qinghuachang Yin group(referred to as the highdose group).On the third day after modeling,corresponding medication was administered for intervention by gavage,once a day,for 14 consecutive days.HE staining method was used to observe the pathological changes of rat colon tissue.The contents of catalase(CAT),glutathione peroxidase 4(GSH-px4),iron ion,myeloperoxidase(MPO),superoxide dismutase(SOD)and lipid peroxide(LPO)in serum were measured.Western blot method was used to detect the expression of NADPH:quinone oxidoreductase-1(NQO-1),hemeoxygenase-1(HO-1)and nuclear factor-erythroid 2-related factor 2(Nrf2)proteins in colon tissue.Results:Compared with the normal group,the levels of serum CAT,GSH-px4,SOD and the protein expression of HO-1,NQO-1,and Nrf2 in the colon tissue of the model group rats significantly reduced(P<0.05),while the levels of serum iron ions,MPO,and LPO significantly increased(P<0.05).Compared with the model group,the levels of serum CAT,GSH px4,SOD and the protein expressions of HO-1,NQO-1 and Nrf2 in colon tissue of rats in the mesalazine and high-dose groups significantly increased(P<0.05),while the levels of iron ion,MPO and LPO significantly reduced(P<0.05).Conclusion:Qinghuachang Yin has an obvious therapeutic effect on ulcerative colitis in rats,the mechanism may be related to the inhibition of oxidative stress based on Nrf2/HO-1 pathway to regulate ferroptosis in intestinal epithelial cells and alleviate ulcerative colitis.

关 键 词：溃疡性结肠炎 清化肠饮 铁死亡 氧化应激 

分 类 号：R285.5[医药卫生—中药学]