中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2014年
8期
1096-1100,1101
,共6页
吴海璇%冯璐璐%徐辉%贺秋兰%李梅娜%魏明%孙来保%邹学农
吳海璇%馮璐璐%徐輝%賀鞦蘭%李梅娜%魏明%孫來保%鄒學農
오해선%풍로로%서휘%하추란%리매나%위명%손래보%추학농
蛇床子素%ERK/MAPK信号通路%COX-2%神经根炎性痛%髓核%脊髓背角
蛇床子素%ERK/MAPK信號通路%COX-2%神經根炎性痛%髓覈%脊髓揹角
사상자소%ERK/MAPK신호통로%COX-2%신경근염성통%수핵%척수배각
osthole%ERK/MAPK signaling pathway%COX-2%inflammatory radicular pain%nucleus pulpo-sus%spinal dorsal horn
目的:观察硬膜外腔给予蛇床子素对髓核致神经根炎性痛大鼠的镇痛作用,及对脊髓背角ERK/MAPK信号通路和COX-2 mRNA表达的影响。方法成年♂ SD大鼠125只,随机分为5组,每组25只,分别为Blank组、Sham组、手术模型组( NP组)、蛇床子素组( Ost组)、溶剂对照组( Vehi-cle组),其中Ost组于术后d 6于硬膜外腔给予50μl蛇床子素1 mg/rat,Vehicle组给予相同体积的溶剂。各组大鼠分别于术前1 d,术后3、6、7、10、14、21 d 测定机械痛阈值(50%MWT),在术后14 d测定机械痛阈后每组随机取15只大鼠,取术侧腰段脊髓背角,Western blot法和荧光定量PCR法检测 ERK、pERK 和 COX-2 mRNA 的表达。结果与Blank组相比,Sham组仅在术后d 150%MWT降低,差异有统计学意义( P<0.05),后逐渐恢复至术前水平, pERK和COX-2 mRNA的表达差异无统计学意义( P>0.05);而 NP组、Vehicle组和 Ost 组术后50% MWT 值明显降低( P <0.05),pERK和COX-2 mRNA的表达明显上调(P<0.05)。硬膜外腔给药后,与 Vehicle组相比, Ost组50%MWT明显升高( P<0.05),给药后d 8 pERK和COX-2 mRNA的表达明显下调(P<0.05)。各组间ERK的表达差异无统计学意义(P>0.05)。对pERK1、pERK2和COX-2 mRNA的表达进行相关性分析,Spearman秩相关系数为0.878(P<0.01)和0.910(P<0.01),表明 pERK和 COX-2 mRNA的表达呈正相关(P<0.05)。结论术后早期应用蛇床子素对髓核导致的神经根炎性痛具有明显的镇痛效应,其机制可能是通过抑制脊髓背角pERK的活化,从而下调COX-2 mRNA的表达。
目的:觀察硬膜外腔給予蛇床子素對髓覈緻神經根炎性痛大鼠的鎮痛作用,及對脊髓揹角ERK/MAPK信號通路和COX-2 mRNA錶達的影響。方法成年♂ SD大鼠125隻,隨機分為5組,每組25隻,分彆為Blank組、Sham組、手術模型組( NP組)、蛇床子素組( Ost組)、溶劑對照組( Vehi-cle組),其中Ost組于術後d 6于硬膜外腔給予50μl蛇床子素1 mg/rat,Vehicle組給予相同體積的溶劑。各組大鼠分彆于術前1 d,術後3、6、7、10、14、21 d 測定機械痛閾值(50%MWT),在術後14 d測定機械痛閾後每組隨機取15隻大鼠,取術側腰段脊髓揹角,Western blot法和熒光定量PCR法檢測 ERK、pERK 和 COX-2 mRNA 的錶達。結果與Blank組相比,Sham組僅在術後d 150%MWT降低,差異有統計學意義( P<0.05),後逐漸恢複至術前水平, pERK和COX-2 mRNA的錶達差異無統計學意義( P>0.05);而 NP組、Vehicle組和 Ost 組術後50% MWT 值明顯降低( P <0.05),pERK和COX-2 mRNA的錶達明顯上調(P<0.05)。硬膜外腔給藥後,與 Vehicle組相比, Ost組50%MWT明顯升高( P<0.05),給藥後d 8 pERK和COX-2 mRNA的錶達明顯下調(P<0.05)。各組間ERK的錶達差異無統計學意義(P>0.05)。對pERK1、pERK2和COX-2 mRNA的錶達進行相關性分析,Spearman秩相關繫數為0.878(P<0.01)和0.910(P<0.01),錶明 pERK和 COX-2 mRNA的錶達呈正相關(P<0.05)。結論術後早期應用蛇床子素對髓覈導緻的神經根炎性痛具有明顯的鎮痛效應,其機製可能是通過抑製脊髓揹角pERK的活化,從而下調COX-2 mRNA的錶達。
목적:관찰경막외강급여사상자소대수핵치신경근염성통대서적진통작용,급대척수배각ERK/MAPK신호통로화COX-2 mRNA표체적영향。방법성년♂ SD대서125지,수궤분위5조,매조25지,분별위Blank조、Sham조、수술모형조( NP조)、사상자소조( Ost조)、용제대조조( Vehi-cle조),기중Ost조우술후d 6우경막외강급여50μl사상자소1 mg/rat,Vehicle조급여상동체적적용제。각조대서분별우술전1 d,술후3、6、7、10、14、21 d 측정궤계통역치(50%MWT),재술후14 d측정궤계통역후매조수궤취15지대서,취술측요단척수배각,Western blot법화형광정량PCR법검측 ERK、pERK 화 COX-2 mRNA 적표체。결과여Blank조상비,Sham조부재술후d 150%MWT강저,차이유통계학의의( P<0.05),후축점회복지술전수평, pERK화COX-2 mRNA적표체차이무통계학의의( P>0.05);이 NP조、Vehicle조화 Ost 조술후50% MWT 치명현강저( P <0.05),pERK화COX-2 mRNA적표체명현상조(P<0.05)。경막외강급약후,여 Vehicle조상비, Ost조50%MWT명현승고( P<0.05),급약후d 8 pERK화COX-2 mRNA적표체명현하조(P<0.05)。각조간ERK적표체차이무통계학의의(P>0.05)。대pERK1、pERK2화COX-2 mRNA적표체진행상관성분석,Spearman질상관계수위0.878(P<0.01)화0.910(P<0.01),표명 pERK화 COX-2 mRNA적표체정정상관(P<0.05)。결론술후조기응용사상자소대수핵도치적신경근염성통구유명현적진통효응,기궤제가능시통과억제척수배각pERK적활화,종이하조COX-2 mRNA적표체。
Aim Toinvestigatetheanalgesiceffectsof epidural osthole application on the mechanical allodyn-ia and the ERK/MAPK signaling pathway and the expression of COX-2 mRNA in the spinal dorsal horn.Methods 125adultmaleSDratswererandomizedin-to five groups( n=25 each) :Blank, Sham, NP, Ost and vehicle. At postoperative day 6, 1mg/rat osthole 50 μl was injected epidurally into group Ost and the same volume of vehicle was given into group vehicle. The mechanical pain threshold was measured by 50%MWT at 1 day before operation and the 3 rd,6 th,7 th, 14 th,21 st day after operation. After the measurement of pain threshold on postoperative day 14 , the L4-6 segment of spinal dorsal horn was removed for determi-nation of the expression of ERK, pERK and COX-2 mRNAbyWesternblotandRT-PCR.Results Com-pared with blank group, the mechanical pain threshold was only down-regulated at day 1 after operation in sham group, the expression of pERK and COX-2 mR-NA in sham group showed no significant difference ( P>0. 05 ); the mechanical pain threshold was signifi-cantly down-regulated after operation in NP, Ost and vehicle groups( P<0. 05 ) and the expression of pERK and COX-2 mRNA was significantly increased ( P <0. 05). Compared with vehicle group, the pain thresh-old in Ost group was significantly increased after drug administration( P<0. 05 ) and the expression of pERK and COX-2 mRNA was significantly reduced ( P <0. 05 ) . The expression of ERK showed no significant difference among each group(P>0. 05). The correla-tion analysis on pERK1/2 and COX-2 mRNA revealed the Pearson correlation coefficient was 0 . 878 and 0 . 910 , suggesting a strong positive correlation between pERKandCOX-2mRNA.Conclusions Ostholead-ministrated in the early stage after surgery can alleviate the nucleus pulposus-induced radicular inflammatory pain probably by inhibiting the expression of pERK and COX-2 mRNA in spinal dorsal horn.