5-氟尿嘧啶联合机械划伤致金黄地鼠口腔黏膜炎模型的建立
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摘要
目的建立5-氟尿嘧啶联合机械划伤致金黄地鼠口腔黏膜炎的模型。方法雄性金黄地鼠分为对照组和模型组,模型组动物分别在第1天和第2天腹腔注射60 mg/kg、40 mg/kg的5-氟尿嘧啶(5-fluorouracil,5-FU),第4天将金黄地鼠右侧颊囊外翻,用18号针头以线性划伤的方式形成口腔浅表划伤。对照组动物分别在第1天和第2天腹腔注射等体积的生理盐水。造模后每天观察各组动物右侧颊囊宏观变化并拍照评分,同时记录体重和每只动物日平均进食量。分别在造模后第8天和第14天取血测定血清中促炎症细胞因子TNF-α和IL-1β的含量,取右侧颊囊组织进行HE染色并测定丙二醛(malondialdehyde,MDA)含量、超氧化物歧化酶(superoxide dismutase,SOD)活性。结果与对照组相比,模型组金黄地鼠在造模后第3天右侧颊囊组织出现溃疡面且宏观评分最高,造模后8 d内动物日平均进食量明显减少且体重下降。造模后第8天和第14天金黄地鼠右侧颊囊组织结构存在损伤,呈现炎症反应,血清中TNF-α、IL-1β的含量均有明显升高,颊囊组织中MDA含量明显升高,SOD活性明显降低。结论 5-氟尿嘧啶联合机械划伤可以导致金黄地鼠口腔黏膜炎的形成,在造模后8 d内炎症反应明显,第3天最明显,可用于口腔黏膜炎发病机制及治疗药物的研究。
Objective To establish a model of oral mucositis in golden hamsters induced by 5-fluorouracil combined with mechanical scratching. Methods Male golden hamsters were divided into a control group and model group.Animals in the model group were intraperitoneally injected with 60 mg/kg and 40 mg/kg of 5-fluorouracil( 5-FU) on the first and second days,and the right cheek pouch was slightly scratched by an 18-gauge needle on the fourth day. The control animals were intraperitoneally injected with an equal volume of normal saline on the first and second days. After the treatment,the pathological changes of the right cheek pouch of each animal were scored every day and the body weight andthe mean daily food intake of each animal were recorded. The level of proinflammatory cytokines TNF-α and IL-1β in the serum was measured by ELISA. The right cheek pouch tissue was removed for pathological examination on days 8 and 14 after the treatment,and the contents of malondialdehyde( MDA) and superoxide dismutase( SOD) activity in the right cheek pouch tissue were determined by biochemical analysis. Results The model group developed an ulcer on the surface of the right cheek pouch on the third day after treatment,and the macroscopic scores of right cheek pouch were the highest compared with the control group. The mean daily food intake was significantly reduced and the body weight was decreased within 8 days after the treatment in the model group. On days 8 and 14 after modeling,the histological structures of the right cheek pouch tissues were damaged and had an inflammatory reaction. The levels of TNF-α and IL-1β in the serum of golden hamsters were significantly increased,the MDA content in the cheek pouch tissue was significantly increased,and the SOD activity was reduced on days 8 and 14. Conclusions 5-fluorouracil combined with mechanical scratching induces the formation of oral mucositis in golden hamsters. The inflammatory response is marked within 8 days after the treatment,and the most obvious is on the third day. Therefore,this model can be used to study the pathogenesis of oral mucositis and for the development of therapeutic drugs.
Objective To establish a model of oral mucositis in golden hamsters induced by 5-fluorouracil combined with mechanical scratching. Methods Male golden hamsters were divided into a control group and model group.Animals in the model group were intraperitoneally injected with 60 mg/kg and 40 mg/kg of 5-fluorouracil( 5-FU) on the first and second days,and the right cheek pouch was slightly scratched by an 18-gauge needle on the fourth day. The control animals were intraperitoneally injected with an equal volume of normal saline on the first and second days. After the treatment,the pathological changes of the right cheek pouch of each animal were scored every day and the body weight andthe mean daily food intake of each animal were recorded. The level of proinflammatory cytokines TNF-α and IL-1β in the serum was measured by ELISA. The right cheek pouch tissue was removed for pathological examination on days 8 and 14 after the treatment,and the contents of malondialdehyde( MDA) and superoxide dismutase( SOD) activity in the right cheek pouch tissue were determined by biochemical analysis. Results The model group developed an ulcer on the surface of the right cheek pouch on the third day after treatment,and the macroscopic scores of right cheek pouch were the highest compared with the control group. The mean daily food intake was significantly reduced and the body weight was decreased within 8 days after the treatment in the model group. On days 8 and 14 after modeling,the histological structures of the right cheek pouch tissues were damaged and had an inflammatory reaction. The levels of TNF-α and IL-1β in the serum of golden hamsters were significantly increased,the MDA content in the cheek pouch tissue was significantly increased,and the SOD activity was reduced on days 8 and 14. Conclusions 5-fluorouracil combined with mechanical scratching induces the formation of oral mucositis in golden hamsters. The inflammatory response is marked within 8 days after the treatment,and the most obvious is on the third day. Therefore,this model can be used to study the pathogenesis of oral mucositis and for the development of therapeutic drugs.
引文
[1]郭燕,黄琰,吴隼,等.化学治疗相关性口腔黏膜炎研究进展[J].新乡医学院学报,2014,31(7):586-589.
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[4]吕丹妮,李容林,杨光伟,等.放射治疗和化学治疗诱发性口腔黏膜炎的防治[J].国际口腔医学杂志,2015,42(2):177-180.
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[6] Skeff MA,Brito GA,de Oliveira MG,et al. S-nitrosoglutathione accelerates recovery from 5-fluorouracil-induced oral mucositis[J]. PLoS One,2014,9(12):e113378.
[7] Rahnama M,Madej-Czerwonka B,Jastrzbska-Jamrogiewicz I,et al. Analysis of the inuence of parenteral cancer chemotherapy on the health condition of oral mucosa[J]. Contemp Oncol(Pozn),2015,19(1):77-82.
[8]王娴.化学治疗所致口腔黏膜炎的防治与进展[J].上海护理,2007,7(1):46-52.
[9] Curra M, Martins MA, Lauxen IS, et al. Effect of topical chamomile on immunohistochemical levels of IL-1βand TNF-αin5-fluorouracil-induced oral mucositis in hamsters[J]. Cancer Chemother Pharmacol,2013,71(2):293-299.
[10] Bayer S,Kazancioglu HO,Acar AH,et al. Comparison of laser and ozone treatments on oral mucositis in an experimental model[J]. Lasers Med Sci,2017,32(3):673-677.
[11] Lima V,Brito GA,Cunha FQ,et al. Effects of the tumour necrosis factor-αinhibitors pentoxifylline and thalidomide in short-term experimental oral mucositis in hamsters[J]. Eur J Oral Sci,2005,113(3):210-217.
[12] Medeiros CA,Leit2o RF,Macedo RN,et al. Effect of atorvastatin on 5-fluorouracil-induced experimental oral mucositis[J]. Cancer Chemother Pharmacol,2011,67(5):1085-1100.
[13] Ahmed AA,Selim MA,El-Sayed NM.α-Lipoic acid ameliorates oral mucositis and oxidative stress induced by methotrexate in rats.Histological and immunohistochemical study[J]. Life Sci,2017,171:51-59.
[14] Koohi-Hosseinabadi O, Ranjba Z, Sepehrimanesh M, et al.Biochemical, hematological, and pathological related healing effects of Elaeagnus angustifolia hydroalcoholic extract in 5-fluorouracil-induced oral mucositis in male golden hamster[J].Environ Sci Pollut Res,2017,24(31):24447-24453.
[15] Vicinus B,Rubie C,Faust SK,et al. MiR-21 functionally interacts with the 3’UTR of chemokine CCL20 and downregulates CCL20 expression in miR-21 transfected colorectal cancer cells[J]. Cancer Lett,2012,316(1):105-112.
[2] Redding SW. Cancer therapy-related oral mucositis[J]. J Dent Educ,2005,69(8):919-929.
[3]刘晓菊,汪秀云.放射及化学治疗所致口腔黏膜炎的护理[J].华西医学,2012,27(6):938-940.
[4]吕丹妮,李容林,杨光伟,等.放射治疗和化学治疗诱发性口腔黏膜炎的防治[J].国际口腔医学杂志,2015,42(2):177-180.
[5]朱丽婵,江子芳,余新燕. 5-氟尿嘧啶化疗致口腔黏膜炎对生活质量的影响[J].护理与康复,2008,7(2):90-92.
[6] Skeff MA,Brito GA,de Oliveira MG,et al. S-nitrosoglutathione accelerates recovery from 5-fluorouracil-induced oral mucositis[J]. PLoS One,2014,9(12):e113378.
[7] Rahnama M,Madej-Czerwonka B,Jastrzbska-Jamrogiewicz I,et al. Analysis of the inuence of parenteral cancer chemotherapy on the health condition of oral mucosa[J]. Contemp Oncol(Pozn),2015,19(1):77-82.
[8]王娴.化学治疗所致口腔黏膜炎的防治与进展[J].上海护理,2007,7(1):46-52.
[9] Curra M, Martins MA, Lauxen IS, et al. Effect of topical chamomile on immunohistochemical levels of IL-1βand TNF-αin5-fluorouracil-induced oral mucositis in hamsters[J]. Cancer Chemother Pharmacol,2013,71(2):293-299.
[10] Bayer S,Kazancioglu HO,Acar AH,et al. Comparison of laser and ozone treatments on oral mucositis in an experimental model[J]. Lasers Med Sci,2017,32(3):673-677.
[11] Lima V,Brito GA,Cunha FQ,et al. Effects of the tumour necrosis factor-αinhibitors pentoxifylline and thalidomide in short-term experimental oral mucositis in hamsters[J]. Eur J Oral Sci,2005,113(3):210-217.
[12] Medeiros CA,Leit2o RF,Macedo RN,et al. Effect of atorvastatin on 5-fluorouracil-induced experimental oral mucositis[J]. Cancer Chemother Pharmacol,2011,67(5):1085-1100.
[13] Ahmed AA,Selim MA,El-Sayed NM.α-Lipoic acid ameliorates oral mucositis and oxidative stress induced by methotrexate in rats.Histological and immunohistochemical study[J]. Life Sci,2017,171:51-59.
[14] Koohi-Hosseinabadi O, Ranjba Z, Sepehrimanesh M, et al.Biochemical, hematological, and pathological related healing effects of Elaeagnus angustifolia hydroalcoholic extract in 5-fluorouracil-induced oral mucositis in male golden hamster[J].Environ Sci Pollut Res,2017,24(31):24447-24453.
[15] Vicinus B,Rubie C,Faust SK,et al. MiR-21 functionally interacts with the 3’UTR of chemokine CCL20 and downregulates CCL20 expression in miR-21 transfected colorectal cancer cells[J]. Cancer Lett,2012,316(1):105-112.