Abstract:

Objective　To investigate the pharmacological effects of halofuginone （HF） on rat models of oral submucous fibrosis （OSF） induced by bleomycin （BLM）. Methods　Forty SD rats were randomly divided into control group（20） and model group（20）. Rats in the model group were treated with 1mg / mL BLM in the bilateral buccal submucosa anesthetized by isoflurane once a day for eight weeks. The control group was given saline instead of BLM. The mouth opening of each rat was measured at 2 weeks, 4 weeks, 6 weeks, and 8 weeks, respectively, and the mean value was drawn after measuring three times for each rat. After 8 weeks，5 rats from the model group were killed and all the rats from the control group were killed, and bilateral buccal mucosa tissues of each killed rat were taken and then fixed in paraformaldehyde. The remaining OSF rats from the model group were randomly divided into control group and HF group，six in each group. Rats from HF group were treated with 200 μL of 1μg/mL halofuginone once a day for six weeks，which was administered in the same way as BLM. The control group were given the same dose of saline. The mouth opening of each rat was measured at 2 weeks, 4 weeks, and 6 weeks with the above-mentioned methods, respectively. After 6 weeks，all the left rats were killed, and bilateral buccal mucosa tissues of each killed rat were taken and then fixed in paraformaldehyde. HE staining was used to detect the histopathological changes in the buccal mucosa of rats. Results　（1）Local injection of BLM for 8 weeks in the buccal mucosa of 20 SD rats induced 17 SD rat models which had clinically and pathologically similar change to human OSF.（2）Halofuginone locally injected for 6 weeks relieved the fibrosis in OSF model rats. Conclusion　Halofuginone can improve the situation of oral submucous fibrosis of SD rats induced by 1 mg/mL BLM，and prevent its further development.

Key words: halofuginone, bleomycin, oral submucous fibrosis, animal model

摘要：

目的　探讨常山酮对博来霉素致口腔黏膜下纤维性变（oral submucous fibrosis，OSF）大鼠的药理作用。方法　将40只SD大鼠随机分为实验组和对照组，每组20只。实验组大鼠在麻醉状态下，于双侧颊黏膜下局部注射1 mg/mL 博来霉素稀释液100 μL，每天1次，共持续给药8周；对照组大鼠注射等量的生理盐水。分别于实验前和给药2、4、6、8周时用游标卡尺对每只大鼠进行张口度测量，每次每只大鼠测量3次，求平均值。建模过程中实验组大鼠有3只死亡。8周后分别处死建模成功的实验组大鼠5只和全部对照组大鼠，取其双侧颊黏膜组织置于多聚甲醛中固定。另建模成功的实验组12只大鼠随机分为常山酮治疗组和常山酮对照组各6只。常山酮治疗组大鼠给予1 μg/mL常山酮稀释液 200 μL，给药方式同建模时博来霉素的注射，每天1次，持续6周；常山酮对照组大鼠给予相同剂量的生理盐水。分别于2、4、6周时对每只大鼠进行张口度测量，测量方法同上。6周后处死全部大鼠，取其双侧颊黏膜组织置于多聚甲醛中固定。采用HE染色观察各组大鼠颊黏膜组织病理变化情况。结果　（1）20只SD大鼠局部注射博来霉素 8周诱导出了17只临床和病理上与人OSF相似改变的SD大鼠模型；（2）局部给药常山酮6周缓解了OSF模型鼠的纤维化情况。结论　常山酮可改善博来霉素致OSF大鼠的纤维化情况，阻止纤维化的进一步发展。

关键词: 常山酮, 博来霉素, 口腔黏膜下纤维性变, 动物模型