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目的评价重组人角质细胞生长因子(rhKGF)对口腔黏膜炎(OM)的预防和治疗作用。方法以MTT法检测rhKGF对32D-KGFR细胞体外增殖的促进作用。大鼠头部经15.3 Gy 60Co辐射制备放射性OM模型,预防组在照射前3 d iv给予rhKGF 0.75,1.5和3 mg.kg-1或帕利非明1.5 mg.kg-1,每天1次,共3次;预防+治疗组在照射前3 d及照射后第2天和第4天iv给予rhKGF 1.5 mg.kg-1,共5次。小鼠iv给予5-氟尿嘧啶50 mg.kg-1,每天1次,连续4 d,制备化疗性OM模型,预防组在化疗开始前3 d iv给予rhKGF1.25,2.5,5 mg.kg-1或帕利非明2.5 mg.kg-1,每天1次,共3次;预防+治疗组在化疗开始前3 d及末次化疗后第2天和第4天iv给予rhKGF 2.5 mg.kg-1,共5次。通过观察临床症状、进食量、体质量变化、死亡率和OM发生率以及组织形态变化评价对OM的预防和治疗作用。结果 rhKGF 6.25～100μg.L-1可促进32D-KGFR细胞增殖反应。在放射性OM模型中,正常对照组、模型组、rhKGF 0.75,1.5和3 mg.kg-1预防组、预防+治疗组及帕利非明预防组大鼠OM发生率分别为0/12,12/12,8/12,6/12,5/12,5/12和5/12,rhKGF 1.5和3.0 mg.kg-1预防组、预防+治疗组和帕利非明预防组在放疗后第6天大鼠进食量显著高于模型组(P<0.05),第6和12天时各给药组体质量均显著高于模型组(P<0.05);另外,各给药组OM症状积分均降低,出现时间延迟,病程缩短。在化疗模型中,正常对照组、模型组、rhKGF预防1.25,2.5,5 mg.kg-1组、预防+治疗组及帕利非明预防组小鼠OM发生率分别为0/16,16/16,10/16,8/16,5/16,10/16和6/16,各给药组在末次化疗后第3和6天能显著缓解化疗引起的进食量减少;与模型组比较,rhKGF和帕利非明预防组小鼠肠黏膜厚度增加,绒毛膜上皮细胞增加,杯状细胞饱满粗大,小肠隐窝深度可见,绒毛形态正常,尤以rhKGF 2.5 mg.kg-1预防组作用最明显;rhKGF预防+治疗组的作用不及同剂量rhKGF预防组。结论rhKGF可预防放射性或化疗所致OM。
Objective To evaluate the preventive and therapeutic effects of recombinant human keratinocyte growth factor (rhKGF) on oral mucositis (OM). Methods MTT assay rhKGF on 32D-KGFR cell proliferation in vitro. The radioactive OM model was prepared by 15.3 Gy 60Co irradiation in the head of rats. The prevention group was given rhKGF 0.75, 1.5 and 3 mg.kg-1 or paclitaxel 1.5 mg.kg-1 three times before the irradiation, once a day, A total of 3 times; prevention + treatment group 3 d before irradiation and 2 and 4 days after irradiation iv given rhKGF 1.5 mg.kg-1, a total of 5 times. Mice were given iv 5-Fluorouracil 50 mg.kg-1 once a day for 4 consecutive days to prepare a chemotherapeutic OM model. The prophylaxis group was given rhKGF 1.25, 2.5, 5 mg.kg -1 Or propriamycin 2.5 mg.kg-1 once a day for 3 times. In the prophylaxis + treatment group, rhKGF 2.5 mg.kg-1 was administrated 3 days before chemotherapy and 2 days and 4 days after the last chemotherapy. , A total of 5 times. To observe the clinical symptoms, food intake, body mass changes, mortality and OM incidence and morphological changes evaluation of the prevention and treatment of OM. Results rhKGF 6.25 ~ 100μg.L-1 could promote the proliferation of 32D-KGFR cells. In the radioactive OM model, the incidences of OM in the normal control group, the model group, the rhKGF 0.75, 1.5 and 3 mg.kg-1 prophylaxis groups, prophylaxis + treatment group and the prophylactoid prophylaxis group were 0/12, 12 / 12,8 / 12,6 / 12,5 / 12,5 / 12 and 5/12, rhKGF 1.5 and 3.0 mg.kg-1 prophylaxis group, prophylaxis + treatment group and prophylactic prophylaxis group after radiotherapy At 6 and 12 days, the body weight of each administration group was significantly higher than that of the model group (P <0.05). In addition, the scores of OM symptom scores in each administration group were significantly higher than those in the model group (P <0.05) Reduce, there is time delay, shorter duration. In the chemotherapy model, the incidence of OM in the normal control group, model group, rhKGF prevention group 1.25, 2.5, 5 mg.kg-1, prophylaxis + treatment group and the prophylactomy group were 0/16, 16, 10/16, 16/16, 16/16, 16/16, and 16/16 respectively. The administration groups significantly reduced the food intake induced by chemotherapy on the 3rd and 6th days after the last chemotherapy. Compared with the model group, In the rhKGF and paclitaxel-prophylaxis groups, the intestinal mucosa thickness increased, the chorionic epithelium cells increased, the goblet cells full and thick, the intestinal crypt depth was visible and the villus morphology was normal, especially rhKGF 2.5 mg.kg-1 Obvious; rhKGF prevention + treatment group than the same dose of rhKGF prevention group. Conclusion rhKGF can prevent radiotherapy or chemotherapy-induced OM.