藏红花酸对急性放射性肠道损伤防治作用及机制  

The protective effect of crocin acid on acuteradiation-induced intestinal injury and its mechanism

作　　者：金秀盈 张欣萍[2] 张百乐 JIN Xiu-ying;ZHANG Xin-ping;ZHANG Bai-le(No.3 Dept of Medical Oncology,Nanyang First People′s Hospital,Nanyang Henan 473000,China;Dept of Gynaecology,Nanyang First People′s Hospital,Nanyang Henan 473000,China;Dept of Radiotherapy,Nanyang First People′s Hospital,Nanyang Henan 473000,China)

机构地区：[1]南阳市第一人民医院肿瘤内三科,河南南阳473000 [2]南阳市第一人民医院妇一科,河南南阳473000 [3]南阳市第一人民医院放疗科,河南南阳473000

出　　处：《中国药理学通报》2025年第3期521-528,共8页Chinese Pharmacological Bulletin

基　　金：江苏省放射医学与防护重点实验室开放基金支持项目(No KJS2242)。

摘　　要：目的探讨藏红花酸(crocetin,Cro)对放射(radiation,RT)引起的急性肠道损伤的防治作用及相关作用机制。方法将40只小鼠随机平均分为4组:对照组、放射组(RT组)、低剂量Cro干预组(RT+Low-dose Cro组)及高剂量Cro干预组(RT+High-dose Cro组)。RT组给予腹部单剂量12Gy放射线照射;Cro干预组于放射线照射前3 d分别灌胃25 mg·kg^(-1)和100 mg·kg^(-1) Cro,每日1次,直到放射后7 d。对各组小鼠进行称质量;HE染色观察肠组织形态;检测小肠炎症因子和氧化应激水平;免疫组织染色小肠组织中Lgr5、Ki67、lysozyme、ZO-1和Occludin表达;Western blot法检测NF-κB及Nrf2/HO-1信号相关蛋白表达。结果与对照组相比,RT组小鼠体质量降低(P<0.01),小肠组织形态明显破坏,促炎症因子(TNF-α、IL-6)和氧化应激(ROS和MDA水平上升、GSH和SOD活性降低)水平上升(P<0.01),隐窝中Lgr5及Ki67阳性细胞减少(P<0.01),小肠组织中Occludin、lysozyme、ZO-1、HO-1表达降低而Nrf2、p-p65和p-IκB表达增高(P<0.01)。与RT组比较,Cro干预组中上述变化均呈现明显改善(P<0.01),高剂量组更显著。结论Cro对放射性肠道损伤具有防治作用,其机制与其抗炎、抗氧化、改善肠屏障功能、促进肠道干细胞再生以及增强Nrf2/HO-1信号并减弱NF-κB信号活性有关。Aim To investigate the preventive and therapeutic effect of crocetin(Cro)on acute intestinal injury induced by radiation(RT)and its related mechanism.Methods Forty mice were randomly divided into four groups:control group,radiation group(RT group),low-dose Cro intervention group(RT+Low-dose Cro group)and high-dose Cro intervention group(RT+High-dose Cro group).The RT group was given a single dose of 12Gy radiation to the abdomen.The Cro intervention group was treated with 25 mg·kg^(-1) and 100 mg·kg^(-1) Cro by gavage once a day before radiation until seven days after radiation.The mice in each group were weighed.The morphology of intestinal tissue was observed by HE staining.The levels of intestinal inflammatory factors and oxidative stress were detected.The expressions of Lgr5,Ki67,lysozyme,ZO-1 and Occludin in small intestine tissuewere detected by immunohistochemistry.The expressions of Nrf2/HO-1 and NF-κB signaling related proteinswere detected by Western blot.Results Compared to the control group,mice in the RT group exhibited a significant decrease in body weight(P<0.01).Additionally,they displayed evident morphological damage to the small intestine and elevated levels of pro-inflammatory factors(TNF-α,IL-6)as well as oxidative stress markers(increased ROS and MDA levels,decreased GSH and SOD activities)(P<0.01).Moreover,there was an increase in Lgr5 and Ki67 positive cells within the crypts(P<0.01).The expressions of Occludin,lysozyme,ZO-1,and HO-1 were reduced in small intestine while Nrf2,p-p65,and p-IκB expressions increased(P<0.01).The improvements in the Cro group were significantly greater than the RT group(P<0.01),with a more pronounced effect observed in the high-dose group.Conclusions Cro has a preventive and therapeutic effect on radiation-induced intestinal injury,and its mechanism is related to anti-inflammation,anti-oxidation,improvement of intestinal barrier function,promotion of intestinal stem cell regeneration,enhancement of Nrf2/HO-1 signaling and reduction of NF-κB signaling activ

关 键 词：藏红花酸 放射性肠炎 肠屏障功能 氧化应激 Nrf2/HO-1 NF-κB 

分 类 号：R-332[医药卫生] R284.1R322.45R641R81