摘要
目的探究右美托咪定(Dexmedetomidine,Dex)通过核因子κB(nuclear factor kappa-B,NF-κB)/疼痛相关趋化因子(CX3C chemokine ligand 1,CX3CL1)途径改善碘乙酸钠(Monosodium iodoacetate,MIA)诱导的骨性关节炎大鼠软骨损伤以及疼痛的分子机制。方法选取健康的SD雄性大鼠50只,随机分为Control组(大鼠不做处理)、Model组(构建MIA诱导的骨性关节炎模型)、Dex组[Model大鼠关节腔内注射Dex(125 mg/kg)],PDTC组[Model大鼠关节腔内注射NF-κB抑制剂PDTC组(2.5 mg/kg)]、Dex+PDTC(Model大鼠关节腔内注射Dex125 mg/kg+PDTC 2.5 mg/kg),每组10只;实验周期为4周。实验结束后测定大鼠机械痛以及冷痛潜伏期;ELISA法检测大鼠关节液内基质金属蛋白酶(MMP-1、MMP-13)、环氧化物酶-2(COX-2)、白细胞介素(IL-1)水平;大鼠行关节软骨组织HE染色,参照Markin评分确定5组软骨损伤;Western-blot检测大鼠关节软骨组织内NF-κB、CX3CL1、Cleaved-caspase-3、Bax等蛋白浓度表达。结果治疗前5组大鼠TWL、MWT差异性小(P>0.05);治疗后,除去Control组,其余4组TWL、MWT均下调(P<0.05);与Control组比较,Model组TWL、MWT下调(P<0.05);与Model组比较,Dex组、PDTC组TWL、MWT上调,二者联合进一步上调TWL、MWT(P<0.05)。与Control组比较,Model组大鼠关节液内MMP-1、MMP-13、COX-2、IL-1均上调(P<0.05);Dex及PDTC的干预可以下调MMP-1、MMP-13、COX-2、IL-1水平(P<0.05);二者联合可以进一步下调MMP-1、MMP-13、COX-2、IL-1水平(P<0.05)。与Control组比较,Model组大鼠软骨关节面出现明显破溃、炎性细胞大量增生现象,Markin评分上调(P<0.05);Dex及PDTC干预后软骨表现破溃、炎性细胞增生程度降低,Markin评分降低(P<0.05);Dex及PDTC二者联合可以进一步改善骨性关节炎大鼠病理状态,降低Markin评分(P<0.05);与Control组比较,Model组大鼠Cleaved-caspase-3、Bax、NF-κB、CX3CL1表达上调(P<0.05);Dex及PDTC的干预可以下调Cleaved-caspase-3、Bax、NF-κB、CX3CL1(P<0.05),二者联�
Objective To explore the molecular mechanism underlying the role of dexmedetomidine(Dex)in alleviating cartilage damage and pain in monosodium iodoacetate(MIA)-induced osteoarthritis rats by regulating the NF-κB(nuclear factor kappa-B)/CX3CL1(CX3C chemokine ligand 1)signaling pathway.Methods The cellular model of osteoarthritis was established by stimulating chondrocytes with IL-1β at 10ng/mL for 24h.The chondrocytes were divided into four groups,including the control group,model group(stimulation of chondrocytes with IL-1β),model+si-negative control(NC)group(transfection with NC siRNA for 48h followed by IL-1β stimulation),and IL-1β+MIR155HG group(transfection with MIR155HG siRNA for 48h followed by IL-1β stimulation).The expression level of MIR155HG was examined using the real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR).The survival rate of chondrocytes was detected using the Calcein acetoxymethyl ester(Calcein AM)cell viability assay kit.The apoptosis of chondrocytes was evaluated using the TdT-mediated dUTP nick end labeling(TUNEL)assay.The protein levels of Bcl-2-associated X protein(Bcl-2),Bcl-2-associated X protein(Bax),matrix metalloproteinase-13(MMP-13),collagen type Ⅱ alpha 1(COL2A1),NLR family pyrin domain containing protein 3(NLRP3),apoptosis associated speck like protein containing a CARD(ASC),and Caspase-1 were measured by Western blotting.The concentrations of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and interleukin-18(IL-18)were quantified by the enzyme-linked immunosorbent assay(ELISA)kits.Results Before treatment,there were no significant differences in thermal withdrawal latency(TWL)and mechanical withdrawal threshold(MWT)in rats among the five groups(P>0.05).After treatment,TWL and MWT in all groups except for control group were significantly reduced(P<0.05).Compared with those of Control group,TWL and MWT were significantly lower in Model group(P<0.05).Compared with those of Model group,TWL and MWT were significantly higher in Dex group and P
作者
管小明
肖扬
苏博源
GUAN Xiaoming;XIAO Yang;SU Boyuan(Department of Anesthesiology,Dongguan TCM Hospital,Guangzhou University of Chinese Medicine,Guangzhou,Dongguan 523000,China;不详)
出处
《河北医药》
CAS
2024年第7期965-970,共6页
Hebei Medical Journal
基金
广东省基础与应用基础研究基金委员会省科技创新战略专项资金(省自然科学基金类)项目(编号:2019A1515011636)。
关键词
骨性关节炎
右美托咪定
碘乙酸钠
软骨损伤
疼痛
osteoarthritis
dexmedetomidine
monosodium iodoacetate
cartilage injury
pain
