Nec-1和Z-VAD-FMK对正畸牙移动中caspase8、MLKL和RANKL表达的影响  

Effects of Nec-1 and Z-VAD-FMK on the Expression of Caspase8,MLKL and RANKL during Orthodontic Tooth Movement

作　　者：李易 王贺 张曼 张严匀 张苗苗[1] LI Yi;WANG He;ZHANG Man(Department of Orthodontics,School of Stomatology,Harbin Medical University,Heilongjiang 150001,China)

机构地区：[1]哈尔滨医科大学口腔医学院正畸科,150001

出　　处：《医学研究杂志》2023年第1期153-157,共5页Journal of Medical Research

摘　　要：目的探讨坏死性凋亡抑制剂Nec-1和凋亡抑制剂Z-VAD-FMK对正畸牙移动(orthodontic tooth movement,OTM)压力侧牙周组织caspase8、混合谱系激酶结构域样蛋白(mixed lineage kinase domain-like protein,MLKL)和核因子κB受体活化因子配体(receptor activator of nuclear factorκB ligand,RANKL)表达的影响。方法构建大鼠上颌左侧第一磨牙OTM模型,根据Nec-1和Z-VAD-FMK的使用情况,将80只健康雄性SD大鼠按随机数字表法分为对照组(C组)、加力组(F组)、加力+Nec-1组(FN组)和加力+Z-VAD-FMK组(FZ组),每组各20只。设定第1、3、5、7、14天5个时间点,采用免疫组化法检测各时间点第一磨牙远中根压力侧caspase8、MLKL和RANKL的表达情况。结果caspase8和RANKL随加力时间的延长均呈现为先增后减的表达趋势,并分别在第3天和第5天出现表达高峰。MLKL则在加力第1天时表达最强,之后逐渐减弱。Nec-1可以抑制MLKL和RANKL的表达,但对caspase8的表达无明显影响。Z-VAD-FMK可以明显抑制caspase8和RANKL的表达,并增强MLKL的表达。结论压力侧牙周组织细胞可同时发生凋亡和坏死性凋亡,抑制凋亡可以促进坏死性凋亡。此外,两者均可引起压力侧牙周组织RANKL高表达,参与牙周组织改建。Objective To investigate the effects of necroptosis inhibitor Nec-1 and apoptosis inhibitor Z-VAD-FMK on the expression of caspase8,mixed lineage kinase domain-like protein(MLKL)and receptor activator of nuclear factorκB ligand(RANKL)of periodontium on the pressure side during orthodontic tooth movement(OTM).Methods The OTM model of the left maxillary first molar of rats was established.According to the use of Nec-1 and Z-VAD-FMK,80 healthy male SD rats were divided into control group(C group),force group(F group),force+Nec-1group(FN group)and force+Z-VAD-FMK group(FZ group)using random number table,20 rats in each group.Five time points on the 1st,3rd,5th,7th and 14th day were set,the expression of caspase8,MLKL and RANKL on the pressure side of the distal root of the first molar were detected by immunohistochemistry at each time point.Results With the extension of time,the expression of caspase8 and RANKL increased at first and then decreased,peaked at 3rd and 5th day,respectively.The expression of MLKL was the strongest at 1st day of after loading,and then decreased gradually.Nec-1 could inhibit the expression of MLKL and RANKL,but had no significant effect on the expression of caspase8.Z-VAD-FMK could significantly inhibit the expression of caspase8 and RANKL,and enhanced the expression of MLKL.Conclusion Apoptosis and necroptosis can occur in periodontium on the pressure side at the same time,and inhibiting apoptosis can promote necroptosis.Moreover,both of them can cause the high expression of RANKL in periodontium on the pressure side and participate in the remodeling of periodontal tissue.

关 键 词：正畸牙移动 凋亡 坏死性凋亡 核因子ΚB受体活化因子配体 

分 类 号：R783.5[医药卫生—口腔医学]