电针调控海马SP/NK1R/ARRB1通路缓解大鼠神经病理性疼痛的研究OA北大核心CSTPCDMEDLINE
Electroacupuncture alleviates neuropathic pain by regulating hippocampal SP/NK1R/ARRB1 pathway
目的:观察电针对坐骨神经慢性缩窄(CCI)大鼠疼痛及焦虑样行为、海马P物质(SP)/神经激肽1受体(NK1R)/β-抑制蛋白1(ARRB1)通路相关蛋白表达的影响,探讨电针治疗神经病理性疼痛(NP)的作用机制.方法:27只雄性SD大鼠随机分为假手术组、模型组和电针组,每组9只.结扎左侧坐骨神经建立CCI模型.电针组大鼠于造模后8 d开始,取术侧"环跳"和"阳陵泉"进行电针治疗,每日30 min,隔日1次,共13次.于术前和术后5、9、17、25、33 d进行机械缩足反射阈值(MWT)、热板缩足反射阈值(TWL)和后肢负重分布差异测试.采用旷场实验评价大鼠焦虑样行为.ELISA法测定海马SP的含量;Western blot法检测海马NK1R、ARRB1的蛋白表达.结果:与假手术组比较,模型组大鼠术后5、9、17、25、33 d左后肢MWT和TWL显著降低(P<0.001,P<0.01)、后肢负重分布差异显著增加(P<0.001),进入中央区域时间和移动总距离显著减少(P<0.001),海马SP的含量降低(P<0.01),海马NK1R、ARRB 1蛋白表达明显增加(P<0.05).与模型组比较,电针组大鼠术后9、17、25、33 d的左后肢MWT和17、25、33 d的TWL显著上升(P<0.01,P<0.001),后肢术后9、17、25、33d的后肢负重分布差异显著减小(P<0.001),进入中央区域时间和移动总距离显著增加(P<0.001),海马SP的含量升高(P<0.05),海马NK1R、ARRB1蛋白表达明显减少(P<0.05).结论:电针"环跳""阳陵泉"可有效改善CCI大鼠的疼痛和焦虑样行为,逆转海马SP、NK1R、ARRB1蛋白的异常表达,提示电针治疗NP的机制可能与调控海马SP/NK1R/ARRB1通路有关.
Objective To observe the effect of electroacupuncture(EA)on pain,anxiety like behavior,and substance P(SP)/neurokinin-1 receptor(NK1R)/β-arrestin 1(ARRB1)pathway related protein expression in hippocampus of chronic constriction injury(CCI)rats,so as to explore its mechanisms underlying improvement of neuropathic pain.Methods Twenty-seven male SD rats were randomly divided into sham operation,model and EA groups,with 9 rats in each group.The CCI model was established by ligature of the left sciatic nerve.On the 8th day following modeling,EA(2 Hz,0.5-1.5 mA)was applied to the left"Huantiao"(GB34)and"Yanglingquan"(GB34)for 30 min,once every other day for 13 times.Mechanical paw withdrawal threshold(MWT),thermal paw withdrawal threshold(TWL)and difference of the weight distribution of the hind limbs were detected before operation and at the 5th,9th,17th,25th and 33rd days after operation.Open field test was used to evaluate the anxiety-like behavior of rats.The content of SP in hippocampus was determined by ELISA.The protein expression of NK1R and ARRB1 in hippocampus was detected by Western blot.Results Compared with the sham operation group,the MWT and TWL of the left hind limb at the 5th,9th,17th,25th and 33rd days after operation,the time of entering the central area and the total distance of movement,and the content of SP in the hippocampus were significantly decreased(P<0.001,P<0.01),while the difference of the weight distribution of the hind limbs at the 5th,9th,17th,25th and 33rd days after operation and the protein expression of NK1R and ARRB1 were significantly increased(P<0.001,P<0.05)in the model group.After EA intervention,the MWT and TWL of the left hind limb,the time of entering the central area and the total moving distance,and the expression of SP in the hippocampus were significantly increased(P<0.01,P<0.001,P<0.05),while the difference in the weight distribution of the hind limbs was significantly reduced,and the expression of NK1R and ARRB1 protein in the hippocampus were significantly decreased(P<0.001,P<0.05)in the EA group.Conclusion EA can effectively improve the pain and anxiety behaviors in CCI rats,and reverse the abnormal expression of SP,NK1R and ARRB1 proteins in the hippocampus,which may be related to its effects in regulating the SP/NK1R/ARRB1 pathway in the hippocampus.
梁嘉仪;王凤娇;王功命;顾意鸣;夏勇;王珂;具紫勇
上海中医药大学针灸推拿学院,上海 201203上海中医药大学附属岳阳中西医结合医院,上海 200437
电针神经病理性疼痛海马P物质神经激肽1受体
ElectroacupunctureNeuropathic painHippocampusSubstance PNeurokinin-1 receptor
《针刺研究》 2024 (008)
829-835 / 7
国家自然科学基金面上项目(No.81874506)
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