摘要
目的探讨川陈皮素(NOB)通过抑制干扰素基因刺激因子(STING)/核转录因子kappaB(NF-κB)信号通路对骨质疏松(OP)大鼠骨折愈合的影响。方法通过切除卵巢+右侧股骨干骨折髓内固定术建立OP性骨折大鼠模型;将造模后的大鼠随机分为模型组、NOB高(NOB-H,30 mg/kg NOB)、中(NOB-M,20 mg/kg NOB)、低剂量(NOB-L,10 mg/kg NOB)组以及NOB-H+STING激活剂(DMXAA)组(30 mg/kg NOB+25 mg/kg DMXAA),并以仅暴露卵巢的18只大鼠作为假手术组。干预结束后,对大鼠骨折愈合状况进行评估;Micro-CT检测大鼠骨小梁微结构变化;试剂盒检测血清中骨代谢相关指标[碱性磷酸酶(ALP)、钙、磷]及炎症因子(TNF-α、IL-1β)水平;HE检测股骨组织形态学变化及骨小梁面积;Western blot检测STING/NF-κB通路相关蛋白表达。结果与对照组相比,模型组骨折线清晰,骨小梁结构紊乱、且间隙较大,TNF-α、IL-1β水平、STING、p-NF-κB p65/NF-κB p65表达显著增加,骨小梁面积、ALP、钙、磷水平、骨密度(BMD)、骨体积分数(BV/TV)、骨小梁数量(Tb.N)和骨小梁厚度(Tb.Th)显著降低(P<0.05);与模型组相比,NOB-L组、NOB-M组、NOB-H组骨折线逐渐模糊,骨小梁结构排列有序,且间隙逐渐减少,指标变化趋势与模型组相反(P<0.05);STING激活剂减弱了NOB对OP大鼠的骨折愈合的促进作用,并增加大鼠炎症反应。结论NOB可减少OP性骨折大鼠炎症反应,促进其骨折愈合,可能与抑制STING/NF-κB信号通路有关。
This study was performed to investigate the impact of nobiletin(NOB)on fracture healing in osteoporosis(OP)rats through the stimulator of interferon gene(STING)/nuclear transcription factor kappa B(NF-κB)signal pathway.A rat model of OP fracture was established by ovariectomy and right femoral shaft fracture intramedullary fixation;the rats after modeling were randomly grouped into model group,high dose(NOB-H,30 mg/kg NOB),medium dose(NOB-M,20 mg/kg NOB),low dose(NOB-L,10 mg/kg NOB)NOB group and NOB-H+STING activator(DMXAA)group(30 mg/kg NOB+25 mg/kg DMXAA),and 18 rats experienced only ovaries expose were used as sham operation group.After the intervention,the fracture healing status of rats were measured;Micro-CT was used to detect the changes of bone trabecular microstructure in rats;commercial kits were used to detect the serum levels of bone metabolism related indicators(alkaline phosphatase(ALP),calcium,phosphorus)and inflammatory factors(tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β));HE was used to detect the morphological changes and trabecular area of femur,while Western blot was applied to detect the expression of STING/NF-κB pathway related proteins.Compared with the control group,the fracture line in the model group was clear,the trabecular structure was disordered and the gap was large,furthermore,the levels of TNF-αand IL-1β,the expression of STING and p-NF-κB p65/NF-κB p65 were significantly increased,the trabecular area,the levels of ALP,calcium,phosphorus,and bone mineral density(BMD),bone volume fraction(BV/TV),bone trabecular number(Tb.N)and bone trabecular thickness(Tb.Th)were significantly decreased(P<0.05);compared with the model group,the fracture line of NOB-L group,NOB-M group and NOB-H group gradually blurred,the trabecular structure arranged orderly,and the gap gradually decreased,and the trend of the index changes mentioned above were opposite to that of the model group(P<0.05).STING activators attenuated the promotion of fracture healing by NOB in OP rats and increased the inflammatory responses.In conclusion,NOB can reduce inflammatory reaction and promote fracture healing in OP rats,which may be related to the inhibition of STING/NF-κB signal pathway.
作者
方红育
黄涛
周少怀
卞峰
任敏
李宏亮
俞诗威
严锦曦
钱慧
李嘉琼
FANG Hongyu;HUANG Tao;ZHOU Shaohuai;BIAN Feng;REN Min;LI Hongliang;YU Shiwei;YAN Jinxi;QIAN Hui;LI Jiaqiong(Department of Orthopaedics,Wuhan Third Hospital,Wuhan 430000,China)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2023年第10期857-864,共8页
Immunological Journal
基金
武汉市医学科研项目(WX19D14)
作者简介
通信作者:周少怀,E-mail:unpqb17@163.com
