归芪白术方不同给药方式通过调节水液代谢改善放射性肠水肿  

Improvement of radiation-induced intestinal edema by regulating water-fluid metabolism in the different administradtion methods of Guiqi Baizhu Formula

作　　者：李洋洋 张利英[1] 刘永琦[1,2] 杨更强 张尚祖 李启杨 王欣 苏海翔[3] LI Yangyang;ZHANG Liying;LIU Yongqi;YANG Gengqiang;ZHANG Shangzu;LI Qiyang;WANG Xin;SU Haixiang(Provincial Key Laboratory of Molecular Medicine and Prevention Research of Major Diseases,Gansu University of Chinese Medicine,Lanzhou 730000,China;Key Laboratory of Dunhuang Medicine and Translational of Ministry of Education,Gansu University of Chinese Medicine,Lanzhou 730000,China;Gansu Provincial Cancer Hospital,Gansu Provincial Institute of Medical Sciences,Lanzhou 730050,China)

机构地区：[1]甘肃中医药大学重大疾病分子医学与防治研究省级重点实验室,兰州730000 [2]甘肃中医药大学敦煌医学与转化教育部重点实验室,兰州730000 [3]甘肃省肿瘤医院,甘肃省医学科学研究院,兰州730050

出　　处：《中华中医药杂志》2024年第7期3743-3748,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：甘肃省优秀博士生项目(No.23JRRA1219);国家自然科学基金项目(No.81960869);兰州市科技计划项目(No.2023-4-52)。

摘　　要：目的:探讨归芪白术方预防性和治疗性给药对放射性肠水肿的保护作用及机制。方法:选择SD大鼠,运用6GyX射线腹部照射建立放射性肠水肿模型,并进行预防性和治疗性给药干预。预防性给药:30只SD大鼠随机分为空白组、模型组和归芪白术方组,每组10只;治疗性给药:120只SD大鼠分为治疗后3d和14d,各60只,随机分为空白组、模型组、纯药组、低剂量组、中剂量组和高剂量组,每组10只。观察大鼠一般状况;检测结肠组织干、湿重;HE染色观察结肠组织形态变化;透射电镜观察结肠组织超微结构;免疫荧光检测结肠组织活性氧(ROS)、缺氧诱导因子1α(HIF-1α)和水通道蛋白4(AQP4)的表达;WesternBlot检测结肠组织AQP4和Na^(+)-K^(+)-ATPase蛋白表达。结果:与空白组比较,模型组结肠组织形态和超微结构出现明显破坏,结肠组织含水量显著升高(P<0.01);ROS、HIF-1α和AQP4表达显著升高(P<0.01);Na^(+)-K^(+)-ATPase蛋白表达显著降低(P<0.01)。与模型组比较,归芪白术方给药(照射前14d,照射后3、14d)干预后,结肠组织形态和超微结构破坏明显好转,归芪白术方治疗性给药3d后,各剂量组结肠组织含水量显著降低(P<0.05,P<0.01);归芪白术方治疗性给药3、14d后,各剂量组ROS、HIF-1α和AQP4表达显著降低(除治疗3d后低剂量组HIF-1α外)(P<0.01),Na^(+)-K^(+)-ATPase蛋白表达显著升高(P<0.01,P<0.05)。结论:无论是预防性还是治疗性给药,归芪白术方均可以有效改善放射性肠水肿,其机制可能是改善缺氧和氧化应激,调控AQP4和Na^(+)-K^(+)-ATPase的表达来实现的。Objective:To investigate the protective effect and mechanism of prophylactic and therapeutic administration of Guiqi Baizhu Formula on radiation-induced intestinal edema.Methods:SD rats were selected to establish a radiation-induced intestinal edema model using 6 Gy X-ray abdominal irradiation,prophylactic and therapeutic drug administration was carried out.Prophylactic administration:Thirty SD rats were randomly divided into blank group,model group and Guiqi Baizhu Formula group,with 10 rats in each group;therapeutic administration:A total of 120 SD rats were randomly divided into two group(3 and 14 d after treatment),and 60 rats in each group,and randomly divided into blank,model,pure drug,low-dose,medium-dose and highdose groups,10 rats in each group.General condition of rats was observed,dry and wet weight of colon tissues were detected,morphological changes of colon tissues were observed by HE staining,ultrastructure of colon tissues was observed by transmission electron microscopy,the expression of reactive oxygen species(ROS),hypoxia-inducible factor Iα(HIF-1α),and aquaporin 4(AQP4)was detected by immunofluorescence,and the expression of AQP4 and Na^(+)-K^(+)-ATPase was detected by Western Blot.Results:Compared with the blank group,the morphology and ultrastructure of colonic tissue in the model group showed significant disruption,and the water content of colonic tissue was significantly elevated(P<0.01),the expression of ROS,HIF-1αand AQP4 was significantly elevated(P<0.01);Na^(+)-K^(+)-ATPase protein expression was significantly reduced(P<0.01).Compared with the model group,the morphological and ultrastructural disruption of colonic tissues was significantly improved after the intervention of the administration of Guiqi Baizhu formula(14 d before irradiation,3 and 14 d after irradiation),and the water content of colonic tissues was significantly reduced in all dose groups after 3 d of the therapeutic administration of Guiqi Baizhu Formula(P<0.05,P<0.01),after 3 and 14 d of therapeutic administration o

关 键 词：水液代谢 归芪白术方 预防性给药 治疗性给药 放射性肠水肿 机制 水通道蛋白4 Na^(+)-K^(+)-ATPase 

分 类 号：R285.5[医药卫生—中药学]