摘要
目的探讨核转录因子-κB(NF-κB)在右美托咪定(Dex)抑制利多卡因对坐骨神经分支损伤(SNI)模型大鼠脊髓神经毒性中作用。方法取40只SD雄性大鼠,随机分为5组:健康对照组(C组)、SNI模型组(S组)、SNI利多卡因组(SL组)、SNI利多卡因+Dex组(SLD组)、SNI利多卡因+Dex+NF-κB阻断剂组(SLDB组),每组8只大鼠。所有大鼠行硬膜外置管,C组未做其他处理。在疼痛稳定后,S组鞘内注射生理盐水20μl,SL组鞘内注射10%利多卡因20μl,SLD组在SL组基础上腹腔注射75μg/kg Dex,SLDB组在SLD组基础上鞘内注射40μg吡咯烷二硫代氨基甲酸酯。连续药物处理7 d后取各组大鼠L4~6节段脊髓,透射电镜观察脊髓形态;末端标记法荧光染色观察脊髓背角细胞凋亡;Western blot检测Bax和Caspase-1表达量;酶联免疫吸附法检测各组脊髓匀浆液中TNF-α和IL-1β的表达。结果 (1)与S组比较,SL组、SLD组及SLDB组的机械痛阈值升高,细胞凋亡数、Bax、Caspase-1、TNF-α及IL-1β表达增加(P<0.05);(2)与SL组比较,SLD组和SLDB组细胞凋亡数、Bax、Caspase-1、TNF-α及IL-1β表达降低(P<0.05);(3)与SLD组比较,SLDB组细胞凋亡数、Bax、Caspase-1、TNF-α及IL-1β表达增加(P<0.05)。结论 Dex抑制利多卡因对SNI模型大鼠脊髓神经毒性可能与激活NF-κB通路、抑制炎症及凋亡有关。
Objective To investigate the role of NF-κB in regulation of Lidocaine-induced spinal cord neurotoxicity of rats with sciatic nerve injury（SNI）. Methods Forty male SD rats were randomly divided into5 groups（8 in each）： healthy control group（group C）, SNI model group（group S）, SNI ＋Lidocaine group（group SL）, SNI ＋Lidocaine ＋Dexmedetomidine group（group SLD）, SNI ＋Lidocaine ＋Dexmedetomidine ＋NF-κB blocker group（group SLDB） with the random number generator in SPSS 17.0 software. All rats had epidural catheterization. But the group C had no other intervention. After the pain was stable, the rats in the group S were intrathecally injected with saline 20 μl, those in the group SL were intrathecally injected with 10%Lidocaine 20 μl, those in the group SLD were intrathecally injected with 10% Lidocaine 20 μl and then intraperitoneally injected with 75 μg/kg Dexmedetomidine, those in the group SLDB were intrathecally injected with 40 μg of Pyrrolidine dithiocarbamate（PDTC） on the basis of the group SLD. The drugs were injected once a day for 7 d. Then L4-L6 segments of the spinal cord were extracted from the rats after anesthesia.Morphological changes of the spinal cord were observed by transmission electron microscope. TUNEL fluorescence staining was used to observe the apoptosis of spinal dorsal horn cells. The expressions of Bax and caspase-1 were detected by Western blot. TNF-α and IL-1β levels in spinal cord homogenate were detected by ELISA. Results Compared with the group S, the mechanical threshold of the groups SL, SLD and SLDB increased, so did the number of apoptic cells and the expressions of Bax, caspase-1, TNF-α and IL-1β（P〈0.05）. Compared with the group SL, the number of apoptic cells and the expressions of Bax, caspase-1, TNF-α and IL-1β in the groups SLD and SLDB decreased（P〈0.05）. Compared with the group SLD, the number of apoptic cells and the expression of Bax, caspase-1, TNF-α and IL-1β increased in the group SLDB（P〈0.05）. Conclusions Activation of NF-κB pathway, inhibition of inflammation and apoptosis may be the mechanism of Dexmedetomidine＇s inhibition of Lidocaine-induced neurotoxicity in SNI model rats.
出处
《中国现代医学杂志》
CAS
北大核心
2017年第23期1-6,共6页
China Journal of Modern Medicine
基金
广西自然科学基金(No:2013GXNSFAA019137)
