新型光敏剂化合物LD4光动力疗法对溃疡性结肠炎大鼠的治疗作用研究  

Effect of new photosensitizer compound LD 4 photodynamic therapy on ulcerative colitis rats

作　　者：荣玉美 洪阁[2] 刘天军[2] Rong Yumei;Hong Ge;Liu Tianjun(The Third Central Hospital of Tianjin,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases,Artificial Cell Engineering Technology Research Center,Tianjin Institute of Hepatobiliary Disease,Tianjin 300170,China;Institute of Biomedical Engineering,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300192,China)

机构地区：[1]天津市第三中心医院,天津市重症疾病体外生命支持重点实验室,天津市人工细胞工程技术研究中心,天津市肝胆疾病研究所,天津300170 [2]中国医学科学院、北京协和医学院生物医学工程研究所,天津300192

出　　处：《国际生物医学工程杂志》2023年第6期514-520,共7页International Journal of Biomedical Engineering

基　　金：天津市卫生健康科技项目(TJWJ2023QN045)。

摘　　要：目的研究新型光敏剂光动力疗法(PDT)对大肠杆菌Escherichia coli诱导的溃疡性结肠炎(UC)模型大鼠的治疗作用。方法每只大鼠灌胃1 ml的1×109个肠侵袭性E.coli建立UC模型。36只Sprague Dawley大鼠随机分为对照组、模型组、新型光敏剂光动力疗法(LD 4-PDT)低、中、高(60、120、240μg/kg)剂量组及左氧氟沙星组(100 mg/kg),每组6只。除对照组一次灌胃0.9%氯化钠注射液外,其余各组建立UC模型。将给予大鼠E.coli的第1天记录为第0天,第7天开始治疗,LD 4灌肠给药,左氧氟沙星灌胃给药,每隔1天灌肠/灌胃1次,共4次。每次给药30 min后,结肠以25 J/cm 2的能量密度接受650 nm激光器PDT系统照射,LEV组不接受照射。比较各组大鼠体质量、结肠长度、肠道病理组织、炎症因子白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)和氧化应激因子髓过氧物酶(MPO)、谷胱甘肽(GSH)和超氧化物歧化酶(SOD)的水平。结果模型组的体质量和结肠长度均低于对照组;LD 4-PDT低、中、高剂量组和左氧氟沙星组的体质量和结肠长度均高于模型组。与对照组相比,模型组多见上皮细胞丢失、多发溃疡、炎症细胞浸润黏膜及黏膜下层、杯状细胞减少;与模型组相比,LD 4-PDT低、中、高剂量组和左氧氟沙星组大鼠结肠组织表面黏膜恢复,杯状细胞增多,溃疡愈合良好。与对照组相比,模型组TNF-α、IL-6和MPO炎症因子水平均升高(均P<0.001);与模型组相比,LD 4-PDT低、中、高剂量组和左氧氟沙星组结肠组织中TNF-α、IL-6和MPO炎症因子水平降低(P<0.05、P<0.001)。与对照组相比,模型组血清中MDA水平升高,GSH和SOD水平降低;与模型组相比,LD 4-PDT低、中、高剂量组MDA水平降低(P<0.05、P<0.001),GSH和SOD水平升高。结论LD 4-PDT可以促进结肠黏膜的愈合,减轻炎症反应,调节氧化应激,从而改善UC症状。ObjectiveTo investigate the therapeutic effects of photodynamic therapy(PDT)on a rat model of ulcerative colitis(UC)induced by Escherichia coli.MethodsEach rat was administered 1 ml of 1×109 enteric invasive E.coli to establish an UC model.Thirty-six Sprague Dawley rats were randomly divided into control,model,low-dose LD 4-PDT,medium-dose LD 4-PDT,high-dose LD 4-PDT(60,120,240μg/kg),and levofloxacin(LEV)(100 mg/kg)groups,with six rats in each group.The UC model was established in all groups except the control group,which received 0.9%sodium chloride injection once.The first day of E.coli administration was recorded as day 0,and treatment was initiated on day 7 with LD 4 enema,levofloxacin gavage,and alternating enema/gavage for a total of four times.After a 30-minute exposure to each dose,the colon was irradiated using a 650 nm laser PDT system with an energy density of 25 J/cm 2,while the LEV group was not irradiated.The levels of body mass,colon length,intestinal pathological tissue,inflammatory factors interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),malondialdehyde(MDA),oxidative stress factors myeloperoxidase(MPO),glutathione(GSH),and superoxide dismutase(SOD)were compared among all groups.ResultsThe body mass and colon length of the model group were lower than those of the control group.The body mass and colon length of the low,medium,and high-dose LD 4-PDT groups and LEV group were higher than those of the model group.Compared to the control group,the model group exhibited more epithelial cell loss,multiple ulcers,infiltration of inflammatory cells into the mucosa and submucosa,and decreased goblet cells.In contrast,the surface mucosa of colon tissue recovered,goblet cells increased,and ulcer healing was good in the low,medium,and high-dose LD 4-PDT groups and LEV group compared to the model group.Compared to the control group,the levels of TNF-α,IL-6,and MPO inflammatory factors were significantly increased in the model group(all P<0.001).Compared to the model group,the levels of TNF-α,IL-6,and M

关 键 词：溃疡性结肠炎 光动力疗法 炎症因子 氧化应激 

分 类 号：R574.62[医药卫生—消化系统]