摘要
目的探究姜黄素(CUR)对牙周炎(PD)小鼠的炎症抑制作用,以及对正畸牙齿移动(OTM)过程中牙槽骨丢失的影响及机制研究。方法100只小鼠随机均分为5组:正常(Con)组(正常小鼠)、PD组(PD小鼠)、OTM组(PD+OTM小鼠)、CUR组(PD+OTM小鼠灌胃100 mg/kg CUR)、CUR+脂多糖(LPS)组(PD+OTM小鼠灌胃100 mg/kg CUR并牙龈注射10μL浓度为1μg/μL的LPS)。除Con组外,其余各组采用左上颌第一磨牙经0.2 mm不锈钢丝进行结扎以诱导PD模型。治疗14 d后,分析牙槽骨的变化;采用HE、抗酒石酸酸性磷酸酶(TRAP)进行组织学分析;ELISA检测牙龈组织中炎症因子[白细胞介素(IL)-6、IL-1β、肿瘤坏死因子-α(TNF-α)]水平;Western blot检测Toll样受体4(TLR4)、髓样分化初级反应基因88(MyD88)、核因子-κB(NF-κB)蛋白表达水平。结果与Con组相比,PD组牙槽骨质界(CEJ)-牙槽骨嵴顶(ABC)距离,组织损伤评分,阳性多核破骨细胞数量,NF-κB受体活化因子配体(RANKL)/骨保护素(OPG)比值,IL-6、IL-1β、TNF-α水平,RANKL、TLR4、MyD88、NF-κB p65表达水平均增加(P<0.05);骨体积分数(BV/TV)、骨小梁的数量(Tb.N)和骨小梁的厚度(Tb.Th)均降低(P<0.05)。与PD组相比,PD+OTM组CEJ-ABC距离,组织损伤评分,阳性多核破骨细胞数量,RANKL/OPG比值,IL-6、IL-1β、TNF-α水平,RANKL、TLR4、MyD88、NF-κB p65表达水平均增加(P<0.05);BV/TV、Tb.N、Tb.Th均降低(P<0.05)。与PD+OTM组相比,PD+OTM+CUR组CEJ-ABC距离,组织损伤评分,阳性多核破骨细胞数量,RANKL/OPG比值,IL-6、IL-1β、TNF-α水平,RANKL、TLR4、MyD88、NF-κB p65表达水平均降低(P<0.05);BV/TV、Tb.N、Tb.Th均增加(P<0.05)。与PD+OTM+CUR组相比,PD+OTM+CUR+LPS组CEJ-ABC距离,组织损伤评分,阳性多核破骨细胞数量,RANKL/OPG比值,IL-6、IL-1β、TNF-α水平,RANKL、TLR4、MyD88、NF-κB p65表达水平均增加(P<0.05);BV/TV、Tb.N和Tb.Th均降低(P<0.05)。结论CUR可抑制炎症因子的释放,下调RANKL/OPG比值,进而减少PD小鼠OMT过程中牙槽骨丢失,其机制可能与调控TLR4/MyD88/NF-κB信号通路有关。
Objective To investigate the anti-inflammatory effects of curcumin(CUR)in a mouse model of periodontitis(PD),and its influence on alveolar bone loss during orthodontic tooth movement(OTM),along with the underlying mechanisms.Methods A total of 100 mice were randomly divided into 5 groups:control(Con)group(normal mice),PD group(induced PD mice),OTM group(PD+OTM mice),CUR group(PD+OTM mice given 100 mg/kg CUR by gavage),and CUR+lipopolysaccharide(LPS)group(PD+OTM mice given 100 mg/kg CUR by gavage and 10μL LPS with a concentration of 1μg/μL by gingival injection).Except for the Con group,the left maxillary first molars were ligated with 0.2 mm stainless steel wire to induce a PD model in the other groups.After 14 days of treatment,the changes of alveolar bone were analyzed.Hematoxylin-eosin(HE)and tartrate-resistant acid phosphatase(TRAP)were used for histological analysis.The levels of inflammatory factors[interleukin(IL)-6,IL-1β,and tumor necrosis factor-α(TNF-α)]in gingival tissues were checked by ELISA.The protein expression levels of Toll-like receptor 4(TLR4),myeloid differentiation primary response gene 88(MyD88),and nuclear factor-κB(NF-κB)were checked by Western blot.Results Compared with the Con group,the PD group exhibited an increased distance between the cementoenamel junction(CEJ)and alveolar bone crest(ABC),higher histopathological damage scores,a greater number of positive multinuclear osteoclasts,and an elevated RANKL/OPG ratio(P<0.05).Additionally,the levels of IL-6,IL-1β,and TNF-α,as well as the expression levels of RANKL,TLR4,MyD88,and NF-κB p65,were upregulated in the PD group(P<0.05).Conversely,the bone volume fraction(BV/TV),trabecular number(Tb.N),and trabecular thickness(Tb.Th)were all reduced in the PD group(P<0.05).Compared with the PD group,the PD+OTM group exhibited increases in the CEJ-ABC distance,histopathological damage scores,number of positive multinuclear osteoclasts,RANKL/OPG ratio,levels of IL-6,IL-1β,and TNF-α,as well as expression levels of RANKL,TLR4,MyD88,and NF-κB p65(P<0.05).In contrast,the BV/TV,Tb.N,and Tb.Th were all reduced in the PD+OTM group(P<0.05).Compared with the PD+OTM group,the PD+OTM+CUR group showed a reduced CEJ-ABC distance,lower histopathological damage scores,a decreased number of positive multinuclear osteoclasts,a decreased RANKL/OPG ratio,reduced levels of IL-6,IL-1β,and TNF-α,and downregulated expression levels of RANKL,TLR4,MyD88,and NF-κB p65(P<0.05).In contrast,the BV/TV,Tb.N,and Tb.Th were all elevated in the PD+OTM+CUR group(P<0.05).Compared with the PD+OTM+CUR group,the PD+OTM+CUR+LPS group showed an increased CEJ-ABC distance,higher histopathological damage scores,an increased number of positive multinuclear osteoclasts,an elevated RANKL/OPG ratio,higher levels of IL-6,IL-1β,and TNF-α,as well as upregulated expression of RANKL,TLR4,MyD88,and NF-κB p65(P<0.05).Furthermore,the PD+OTM+CUR+LPS group showed decreases in BV/TV,Tb.N,and Tb.Th(P<0.05).Conclusion CUR can inhibit the release of inflammatory factors,downregulate RANKL/OPG ratio,and reduce alveolar bone loss during OTM in PD mice.The mechanism may be related to the regulation of TLR4/MyD88/NF-κB signaling pathway.
作者
江淑敏
于晓艳
李海梅
李世光
IANG Shumin;YU Xiaoyan;LI Haimei;LI Shiguang(Department of Stomatology,Wu'an First People's Hospital,Handan,Hebei 056300,China)
出处
《湖南中医药大学学报》
2025年第7期1203-1209,共7页
Journal of Hunan University of Chinese Medicine
基金
河北省医学科学研究课题计划(20191656)。
