莫西沙星辅助多光子成像用于溃疡性结肠炎的诊断研究
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摘要
目的:探索莫西沙星辅助多光子显微成像(multiphoton microscopic imaging,MPM)在小鼠溃疡性结肠炎中应用的可行性,总结结肠炎小鼠MPM辅助诊断特征。方法:将32只Balb/c小鼠随机分为对照组、急性期结肠炎组、缓解期结肠炎组和慢性期结肠炎组,每组8只,饮用3%葡聚糖硫酸钠溶液建立结肠炎模型,经病理证实各组小鼠均造模成功。对各小鼠结肠组织行MPM成像,再将同一结肠组织在0.16%莫西沙星溶液中浸泡2 min,再行MPM成像。比较未经莫西沙星处理和经莫西沙星处理的结肠组织MPM清晰成像所需激发功率以及相同激发功率下未经莫西沙星处理和经莫西沙星处理的MPM图像荧光强度;比较莫西沙星处理后各模型组结肠组织荧光增强区域所占比例;归纳不同溃疡性结肠炎模型未经莫西沙星处理和经莫西沙星处理的MPM成像特征。结果:在能看到清晰图像的情况下,未经莫西沙星处理和经莫西沙星处理的对照组小鼠MPM成像所需的激发光功率分别为(2.78±0.04)mW、(0.28±0.01)mW,两者差异具有统计学意义(P <0.05);相同激发功率下,未经莫西沙星处理和经莫西沙星处理的对照组小鼠MPM平均荧光强度分别为(1 313.99±164.52)a.u.、(3 896.43±87.55)a.u.,两者差异具有统计学意义(P <0.05);经莫西沙星处理的对照组、急性期结肠炎组、缓解期结肠炎组、慢性期结肠炎组的平均荧光增强区域所占比例分别为(22.4±1.6)%、(7.7±1.0)%、(13.5±1.7)%、(5.0±1.3)%,后3组与对照组的差异均有统计学意义(P <0.05)。莫西沙星可辅助MPM清晰成像组织隐窝开口、腺体结构、相邻腺体间隙和荧光增强区域等。结论:莫西沙星可有效提高MPM成像效率,并呈现独特的组织功能性鉴别特征,结合多维度的量效和结构特征,可有效鉴别溃疡性结肠炎小鼠。
引文
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[2] Rubin DC,Shaker A,Levin MS. Chronic intestinal inflam-mation:inflammatory bowel disease and colitis-associated colon cancer[J]. Front Immunol,2012,3:107
[3] Wei SC,Chang TA,Chao TH,et al. Management of ulcer-ative colitis in Taiwan:consensus guideline of the Taiwan society of inflammatory bowel disease[J]. Intest Res,2017,15(3):266-284
[4] Cheon JH. Advances in the endoscopic assessment of in-flammatory bowel diseases:cooperation between endo-scopic and pathologic evaluations[J]. J Pathol Transl Med,2015,49(3):209-217
[5] Gabbani T,Manetti N,Bonanomi AG,et al. New endoscop-ic imaging techniques in surveillance of inflammatory bowel disease[J]. World J Gastrointest Endosc,2015,7(3):230-236
[6] Stefanescu D,Pereira SP,Filip MM,et al. Advanced endo-scopic imaging techniques for the study of colonic mucosa in patients with inflammatory bowel disease[J]. Rom J In-tern Med,2016,54(1):11-23
[7] Kim ES. Role of advanced endoscopic imaging techniques in the management of inflammatory bowel disease[J].Clin Endosc,2017,50(5):424-428
[8] Rasmussen DN,Karstensen JG,Riis LB,et al. Confocal la-ser endomicroscopy in inflammatory bowel disease-a sys-tematic review[J]. J Crohns Colitis,2015,9(12):1152-1159
[9] Lord R,Burr NE,Mohammed N,et al. Colonic lesion char-acterization in inflammatory bowel disease:A systematic review and meta-analysis[J]. World J Gastroenterol,2018,24(10):1167-1180
[10] Maione F,Giglio MC,Luglio G,et al. Confocal laser endo-microscopy in ulcerative colitis:beyond endoscopic as-sessment of disease activity[J]. Tech Coloproctol,2017,21(7):531-540
[11]何可心,赵黎黎,黄晓阳,等.多光子显微成像技术用于诊断结直肠疾病可行性的初步研究[J].南京医科大学学报(自然科学版),2018,38(3):201-205,238
[12] Rogart JN,Nagata J,Loeser CS,et al. Multiphoton imag-ing can be used for microscopic examination of intact hu-man gastrointestinal mucosa ex vivo[J]. Clin Gastroenter-ol Hepatol,2008,6(1):95-101
[13] Waldner MJ,Rath T,Schurmann S,et al. Imaging of mu-cosal inflammation:current technological developments,clinical implications,and future perspectives[J]. Front Immunol,2017,8:1256
[14] Makino T,Jain M,Montrose DC,et al. Multiphoton tomo-graphic imaging:a potential optical biopsy tool for detect-ing gastrointestinal inflammation and neoplasia[J]. Can-cer Prev Res(Phila),2012,5(11):1280-1290
[15] Lee S,Lee JH,Park JH,et al. In vivo 3D measurement of moxifloxacin and gatifloxacin distributions in the mouse cornea using multiphoton microscopy[J]. Sci Rep,2016,6:25339
[16]Wang T,Jang WH,Lee S,et al. Moxifloxacin:Clinically compatible contrast agent for multiphoton imaging[J]. Sci Rep,2016,6:27142
[17]Lee JH,Le VH,Lee S,et al. Two-photon microscopy of fungal keratitis-affected rabbit cornea ex vivo using moxi-floxacin as a labeling agent[J]. Exp Eye Res,2018,174:51-58
[18] Jang WH,Park A,Wang T,et al. Two-photon microscopy of Paneth cells in the small intestine of live mice[J]. Sci Rep,2018,8(1):14174
[19]Lee JH,Kim KH,Lee S,et al. Two-photon microscopy of the mouse peripheral cornea ex vivo[J]. Cornea,2016,35(Suppl 1):S31-S37
[20] Wirtz S,Popp V,Kindermann M,et al. Chemically in-duced mouse models of acute and chronic intestinal in-flammation[J]. Nat Protoc,2017,12(7):1295-1309
[21]Cui G,Yuan A. A systematic review of epidemiology and risk factors associated with chinese inflammatory bowel disease[J]. Front Med(Lausanne),2018,5:183
[22]Schurmann S,Foersch S,Atreya R,et al. Label-free imag-ing of inflammatory bowel disease using multiphoton mi-croscopy[J]. Gastroenterology,2013,145(3):514-516
[23] Drlica K,Zhao X. DNA gyrase,topoisomeraseⅣ,and the4-quinolones[J]. Microbiol Mol Biol Rev,1997,61(3):377-392
[24] Wirtz M,Kleeff J,Swoboda S,et al. Moxifloxacin penetra-tion into human gastrointestinal tissues[J]. J Antimicrob Chemother,2004,53(5):875-877