摘要
目的通过槟榔提取物构建大鼠口腔溃疡模型,观察口腔内菌群结构变化及多样性特征,探索口腔菌群和局部炎性因子参与槟榔提取物诱发大鼠口腔溃疡的发病作用机制研究,为临床防治口腔溃疡提供理论支持。方法将30只SD大鼠随机分为正常组、模型组、药物治疗组(桂林西瓜霜,8 mg/d,连续7 d),10只/组。大鼠口腔黏膜经皮下注射10 g/mL的槟榔提取物,复制大鼠口腔溃疡模型。通过观察溃疡面积、溃疡评分、局部组织口腔肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-2(interleukin-2,IL-2)、IL-8水平,并取口腔黏膜组织进行HE染色,观察其组织形态学的变化,采用高通量测序方法分析口腔微生物菌群结构分布及微生物群落多样性。结果与正常组比较,模型组大鼠溃疡面积显著增大,溃疡评分显著上升(P<0.01),口腔黏膜组织TNF-α、IL-2、IL-8水平均显著升高(P<0.01),大鼠口腔唾液的链球菌属(Streptococcus,P<0.05)、韦荣球菌属(Veillonella,P<0.001)均显著减少,模型组大鼠口腔黏膜上皮细胞增生或局灶性坏死,黏膜固有层水肿、出血,并伴有大量的中性粒细胞和单核细胞浸润;与模型组比较,药物治疗组大鼠溃疡面积显著减少(P<0.05,P<0.01),溃疡评分显著减少(P<0.05),口腔黏膜组织TNF-α(P<0.01)、IL-2(P<0.05)、IL-8(P<0.05)水平均显著降低,大鼠口腔唾液的链球菌属(Streptococcus,P<0.001)、韦荣球菌属(Veillonella,P<0.01)显著增加,葡萄球菌属(Staphylococcus,P<0.01)显著减少,口腔黏膜组织病变程度有明显改善。结论槟榔提取物可成功复制大鼠口腔溃疡模型,其发病机制可能与口腔正常菌群水平降低,潜在致病菌水平升高,破坏其口腔菌群微生物平衡,进而破坏机体免疫系统,引起局部促炎因子升高有关。
Objective A model for studying oral ulcers induced by betel nut-extract was constructed in rats.Changes in the structure and diversity of oral flora were observed to explore the involvement of oral flora and local inflammatory factors in the pathogenesis of oral ulcers induced by betel nut-extract and to provide theoretical support for the prevention and treatment of oral ulcers in the clinic.Methods Thirty SD rats were randomly divided into normal,model and intervention groups(Guilin watermelon cream,8 mg/d for 7 days),with 10 rats/group.The oral mucosa of rats was subcutaneously injected with 10 g/mL of betel nut-extract to generate an oral ulcer model.The histomorphological changes were observed,and ulcer area and ulcer scores were assessed.Local oral tissue tumor necrosis factor-α(TNF-α),interleukin(IL)-2 and IL-8 levels were determined.Oral mucosal tissues were sampled for HE staining and analyzed for the structural distribution of oral flora and the diversity of microbial communities using high-throughput sequencing method.Results Compared with rats in the normal group,those in the model group had an increased ulcer area,significantly increased ulcer scores(P<0.01),and significantly increased levels of TNF-α,IL-2 and IL-8 in the oral mucosal tissues(P<0.01).The amount Streptococcus(P<0.05)and Veillonella(P<0.001)in the oral saliva of the model group rats was significantly reduced.The model group rats showed oral mucosal epithelial cell hyperplasia or focal necrosis,mucosal lamina propria edema,and hemorrhage accompanied by mass neutrophil and monocyte infiltration.Compared with the model group rats,the intervention group rats had significantly reduced ulcerated area(P<0.05,P<0.01)and ulcer scores(P<0.05).And oral mucosal tissue levels of TNF-α(P<0.01),IL-2(P<0.05)and IL-8(P<0.05),as well as significantly increased Streptococcus(P<0.001)and Veillonella(P<0.01)and significantly reduced Staphylococcus(P<0.01)in the oral saliva.The degree of lesions in the oral mucosal tissues was significantly improved in the intervention group.Conclusions Betel nut-extract can be used to successfully reproduce a rat model of oral ulcer,and it is speculated that the development of oral ulcers after exposure to betel nut-extract may be related to an imbalance in the oral flora and local tissue inflammatory mediators.
作者
彭冬冬
陈相池
唐梓宁
刘学武
袁湘中
李萌
厉巧
章泽恒
PENG Dongdong;CHEN Xiangchi;TANG Zining;LIU Xuewu;YUAN Xiangzhong;LI Meng;LI Qiao;ZHANG Zeheng(Hunan Prima Drug Research Center Co.Ltd,Changsha 410329;China.2.Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs,Changsha 410329;.3.Drug Evaluation and Adverse Drug Reaction Monitoring Center of Hunan Province,Changsha 410000)
出处
《中国比较医学杂志》
CAS
北大核心
2024年第1期52-59,共8页
Chinese Journal of Comparative Medicine
基金
湖南普瑞玛新药非临床研究创新创业团队(2021)。
关键词
槟榔提取物
口腔溃疡
口腔菌群
炎性因子
大鼠
betel nut-extract
oral ulcer
oral flora
inflammatory factors
rat Conflicts of Interest:The authors declare no conflict of interest.
