中华麻醉学杂志
中華痳醉學雜誌
중화마취학잡지
CHINESE JOURNAL OF ANESTHESIOLOGY
2014年
7期
789-792
,共4页
电刺激%神经痛%脊髓%高迁移率族蛋白类%Toll样受体4%NF-κB
電刺激%神經痛%脊髓%高遷移率族蛋白類%Toll樣受體4%NF-κB
전자격%신경통%척수%고천이솔족단백류%Toll양수체4%NF-κB
Electric stimulation%Neuralgia%Spinal cord%High mobility group proteins%Toll-like receptor 4%NF-kappaB
目的 探讨脊髓电刺激减轻大鼠神经病理性痛的机制与脊髓高迁移率族蛋白B1(HMGB1)/Toll样受体4(TLR4)/NF-κB信号通路的关系.方法 健康雄性SD大鼠48只,8周龄,体重250 ～ 300 g,采用随机数字表法将其分为4组(n=12):假手术组(S组)、坐骨神经慢性结扎组(CCI组)、假脊髓电刺激组(S-SCS组)和脊髓电刺激组(SCS组).采用坐骨神经慢性结扎的方法制备大鼠神经病理性痛模型.S-SCS组和SCS组于造模后第5天在脊髓硬膜外间隙置入电极,SCS组于造模后12-14 d行脊髓电刺激.分别于造模前1d、造模后1、4、7、14 d测定机械缩足反应阈(MWT).于造模后14 d行为学测定结束后处死大鼠,取L4-6脊髓组织,采用实时荧光定量PCR法测定脊髓组织HMGB1、TLR4、NF-κB p65的mRNA表达,采用Western blot法测定脊髓组织TLR4蛋白和核蛋白NF-κB p65表达,采用免疫组化法测定脊髓组织HMGB1蛋白表达.结果 与S组相比,CCI组、S-SCS组和SCS组造模后MWT降低,脊髓组织HMGB1、TLR4的mRNA及其蛋白表达上调,NF-κB p65 mRNA和核蛋白NF-κB p65表达上调(P＜0.05);与CCI组相比,SCS组脊髓电刺激后MWT升高,脊髓组织HMGB1、TLR4的mRNA及其蛋白表达下调,NF-κB p65 mRNA和核蛋白NF-κB p65表达下调(P＜0.05).结论 脊髓电刺激减轻大鼠神经病理性痛的机制可能与抑制脊髓HMGB1/TLR4/NF-κB信号通路有关.
目的 探討脊髓電刺激減輕大鼠神經病理性痛的機製與脊髓高遷移率族蛋白B1(HMGB1)/Toll樣受體4(TLR4)/NF-κB信號通路的關繫.方法 健康雄性SD大鼠48隻,8週齡,體重250 ～ 300 g,採用隨機數字錶法將其分為4組(n=12):假手術組(S組)、坐骨神經慢性結扎組(CCI組)、假脊髓電刺激組(S-SCS組)和脊髓電刺激組(SCS組).採用坐骨神經慢性結扎的方法製備大鼠神經病理性痛模型.S-SCS組和SCS組于造模後第5天在脊髓硬膜外間隙置入電極,SCS組于造模後12-14 d行脊髓電刺激.分彆于造模前1d、造模後1、4、7、14 d測定機械縮足反應閾(MWT).于造模後14 d行為學測定結束後處死大鼠,取L4-6脊髓組織,採用實時熒光定量PCR法測定脊髓組織HMGB1、TLR4、NF-κB p65的mRNA錶達,採用Western blot法測定脊髓組織TLR4蛋白和覈蛋白NF-κB p65錶達,採用免疫組化法測定脊髓組織HMGB1蛋白錶達.結果 與S組相比,CCI組、S-SCS組和SCS組造模後MWT降低,脊髓組織HMGB1、TLR4的mRNA及其蛋白錶達上調,NF-κB p65 mRNA和覈蛋白NF-κB p65錶達上調(P＜0.05);與CCI組相比,SCS組脊髓電刺激後MWT升高,脊髓組織HMGB1、TLR4的mRNA及其蛋白錶達下調,NF-κB p65 mRNA和覈蛋白NF-κB p65錶達下調(P＜0.05).結論 脊髓電刺激減輕大鼠神經病理性痛的機製可能與抑製脊髓HMGB1/TLR4/NF-κB信號通路有關.
목적 탐토척수전자격감경대서신경병이성통적궤제여척수고천이솔족단백B1(HMGB1)/Toll양수체4(TLR4)/NF-κB신호통로적관계.방법 건강웅성SD대서48지,8주령,체중250 ～ 300 g,채용수궤수자표법장기분위4조(n=12):가수술조(S조)、좌골신경만성결찰조(CCI조)、가척수전자격조(S-SCS조)화척수전자격조(SCS조).채용좌골신경만성결찰적방법제비대서신경병이성통모형.S-SCS조화SCS조우조모후제5천재척수경막외간극치입전겁,SCS조우조모후12-14 d행척수전자격.분별우조모전1d、조모후1、4、7、14 d측정궤계축족반응역(MWT).우조모후14 d행위학측정결속후처사대서,취L4-6척수조직,채용실시형광정량PCR법측정척수조직HMGB1、TLR4、NF-κB p65적mRNA표체,채용Western blot법측정척수조직TLR4단백화핵단백NF-κB p65표체,채용면역조화법측정척수조직HMGB1단백표체.결과 여S조상비,CCI조、S-SCS조화SCS조조모후MWT강저,척수조직HMGB1、TLR4적mRNA급기단백표체상조,NF-κB p65 mRNA화핵단백NF-κB p65표체상조(P＜0.05);여CCI조상비,SCS조척수전자격후MWT승고,척수조직HMGB1、TLR4적mRNA급기단백표체하조,NF-κB p65 mRNA화핵단백NF-κB p65표체하조(P＜0.05).결론 척수전자격감경대서신경병이성통적궤제가능여억제척수HMGB1/TLR4/NF-κB신호통로유관.
Objective To investigate the relationship between the mechanism of mitigation of neuropathic pain by spinal cord stimulation (SCS) and high mobility group protein box-1 (HMGB1)/Toll-like receptor 4 (TLR4)/NF-κB signaling pathway in the spinal cord of rats.Methods Forty-eight male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were randomly divided into 4 groups (n =12 each) using a random number table:sham operation group (S group),chronic constrictive injury (CCI) group,sham SCS group (S-SCS group),and SCS group.Neuropathic pain was induced by CCI in the animals anesthetized with intraperitoneal chloral hydrate.The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread.Electrodes were placed into the epidural space at 5 days after CCI in S-SCS and SCS groups,and in addition SCS was performed at 12-14 days after CCI in SCS group.Paw withdrawal threshold to mechanical stimulation (MWT) were measured at 1 day before operation and 1,4,7,14 days after CCI.After measurement of pain threshold at day 14 after CCI,the animals were sacrificed and the lumbar segments (L4-6) of the spinal cord were obtained for determination of mRNA expression of HMGB1,TLR4,and NF-κB p65 (in the nuclear protein,by real-time fluorescent quantitative PCR),protein expression of TLR4 and NF-κBp65 (by Western blot),and protein expression of HMGB1 (by immunohistochemistry).Results Compared with S group,MWT was significantly decreased after CCI,the mRNA and protein expression of HMGB1 and TLR4 was up-regulated,and the expression of NF-κB p65in the nuclear protein and mRNA was up-regulated in CCI,S-SCS and SCS groups.Compared with CCI group,MWT was significantly increased after spinal cord stimulation,the mRNA and protein expression of HMGB1 and TLR4 was down-regulated,and the expression of NF-κB p65 in the nuclear protein and mRNA was down-regulated in SCS group.Conclusion The mechanism by which SCS mitigates neuropathic pain may be related to inhibition of HMGB1/TLR4/NF-κB signaling pathway in the spinal cord of rats.
