二甲双胍对大鼠口腔黏膜溃疡的疗效之组织学评价

Therapeutic Potentials of Metformin in Management of Oral Mucosal Ulcer in Rats:a Histological Study

目的:探索二甲双胍(MET)对口腔黏膜溃疡(OMU)的疗效。方法:创伤法在SD大鼠(n=24)两侧颊黏膜建立OMU模型。24h后(d1),左侧(MET侧)溃疡基底每天注射20μmol/LMET溶液,右侧(对照侧)注射生理盐水,记录溃疡面积。d2、d4、d7分别处死8只,行溃疡组织切片染色,分析新生上皮厚度和比例、结缔组织炎细胞数和胶原纤维含量。结果:d1时,同侧溃疡面积均匀,两侧面积等大(P=0.935)。d2~d7,溃疡面积不断缩小(P<0.05),胶原纤维含量和新生上皮厚度不断上升;炎细胞数于d2~d4上升,d4~d7下降(P<0.05)。d2~d5,MET侧溃疡面积小于对照侧16%~37%(P<0.05),d6~d7则不显著。d1~d7,MET侧炎细胞数小于对照侧(P<0.05)。d2~d4,MET侧胶原纤维含量和新生上皮厚度高于对照侧(P<0.05),此优势在d4~d7不再显著。结论:MET对早期OMU有明显改善作用,可能与抑制炎症,促进组织修复有关。

Objective: To explore the effects of metformin (MET) on oral mucosal ulcer (OMU).Methods: OMU models were established with trauma at bilateral buccal mucosa in SD rats (n=24).After 24 hours (d 1),20 μmol/L MET solution was injected into the ulcer base of left side (MET side) one time per day,with normal saline injected into the right side as the control.The rats were sacrificed at d 2,d 4,and d 7,8 rats for each time point.Ulcer size was recorded every day.Thickness and proportion of new epithelium,inflammatory cell number in connective tissue,and collagen fiber content were analyzed.Results: At d 1,ulcer size showed good consistency within the same sides and between the bilateral sides ( P =0.935).From d 2 to d 7,ulcer size was reduced ( P <0.05) and collagen fiber content and thickness of new epithelium were increased persistently.Inflammatory cell number was increased from d 2 to d 4 and then decreased from d 4 to d 7 ( P <0.05).Ulcer size was 16% to 37% smaller at MET side from d 2 to d 5 than that of control side ( P <0.05),which was comparable bilaterally from d 6 to d 7.Inflammatory cell number was down regulated from d 1 to d 7 at MET side relative to that of control side ( P <0.05).Collagen fiber content and thickness of new epithelium was upregulated at MET side from d 2 to d 4 compared with those at control side ( P <0.05),which showed no difference bilaterally from d 4 to d 7.Conclusion: MET shows significant improving effect on OMU at early stages,which might relate to the inflammatory inhibition and reparative promotion.