芍药甘草汤对坐骨神经慢性压迫性损伤大鼠痛阈和脊髓SIRT1表达的影响  被引量:9

Role of SIRT1 in the Extracts of the Chinese Medicine Shaoyao and Gancao in Chronic Constriction Injury-Induced Neuropathic Pain in Rats

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作  者:张娟[1] 马千[1] 吕晨[1] 赵莉[1] 谢晓燕[1] 郭小文[1] 

机构地区:[1]浙江中医药大学附属第一医院,杭州310006

出  处:《浙江中医药大学学报》2015年第5期329-334,共6页Journal of Zhejiang Chinese Medical University

基  金:国家自然基金(81202823/H2902);浙江省医药卫生科技计划(2014KYA157);浙江省科技厅创新团队课题(2011R50022-2)~~

摘  要:[目的]观察芍药甘草汤(shaoyao-gancao decoction,SGD)对坐骨神经慢性压迫性损伤(chronic constriction injury,CCI)大鼠机械痛敏和热痛敏的影响,并研究SGD对CCI大鼠脊髓沉默信息调节因子2相关酶1(silent mating type information regulation 2 homolog 1,SIRT1)表达的影响。[方法]SD大鼠随机分为5组:假手术组(Sham组)、CCI组、SGD组、SGD+SIRT1-si RNA(small-interfering RNA,si RNA)和SGD+MM-si RNA(阴性对照)组,SGD组大鼠在CCI模型建立前6h开始灌胃给予40g·kg-1 SGD,1次/d,连续4d,而Sham组和CCI组大鼠则灌胃给予同体积的0.9%生理盐水;SGD+SIRT1-si RNA组大鼠除灌胃给予40g·kg-1 SGD,还鞘内给予10μL(2.5μg)的SIRT1-si RNA,SGD+MM-si RNA组则给予同剂量的MM-si RNA。各组分别在术前和术后第1、3、5、7d测定机械缩足反射阈值(mechanical withdrawal threshold,MWT)和热缩足潜伏期(thermal withdrawal latency,TWL),手术结束后提取大鼠脊髓测定SIRT1和Ac-NF-κB/NF-κB的蛋白表达。[结果]和Sham组相比,CCI组术后MWT及TWL均下降(P<0.05),SGD组与CCI组相比,MWT和TWL在术后1、3和7d均明显增加(P<0.05)。和Sham组相比,CCI组SIRT1和Ac-NF-κB/NF-κB表达降低(P<0.01),和CCI组比较,SGD+SIRT1-si RNA组SIRT1和Ac-NF-κB/NF-κB表达增加(P<0.01),而鞘内预先给予SIRT1 si RNA组则可逆转SGM的作用(P<0.05,P<0.01)。[结论]SGD能抑制CCI大鼠的机械痛敏和热痛敏,其作用可能和增加脊髓SIRT1的表达有关。Objective] To observe the effect and the SIRT1 expression of the extracts of the Chinese medicine shaoyao and gancao(SGD) on mechanical allodynia and heat hyperalgesia induced by chronic constriction injury(CCI) of the sciatic nerve in rats. [Methods] Mechanical allodynia and heat hyperalgesia were evaluated by mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL) respectively. Rats were divided randomly into five groups for Sham group, CCI group, SGM group, SGD+MM-siRNA group and SGD+SIRT1-siRNA group. SGD was given to rats from day 0(6h before CCI surgery) to day 3 post-CCI surgery via gastric infusion, in dosage of 40g of crude drug/kg per day, 0.9%saline with the equal volume given to Sham and CCI groups. Mismatch siRNA and SIRT1 siRNA were given once daily, from the day before CCI to after CCI 3 days. The animals received intrathecal injections(2.5μg siRNA/10μL/rat) of either SIRT1-selective siRNA mixture(SGD+SIRT1-siRNA group) or i-Fect non-targeting dsRNA(SGD+MM-siRNA group). The TWL and MWT were measured before surgery and on days 1, 3, 5 and 7 after surgery. [Results] Compared with Sham group, rats with CCI significantly decreased PWL and PWT from the first day after surgery to the end of this study(P〈0.01). Compared with CCI group, SGM group increased the MWT and TWL(P〈0.05). In contrast to Sham group, remarkably decreased SIRT1 and Ac-NF-κB /NF-κB intensity was observed in the ipsilateral spinal cord of rats in the CCI group(P〈0.01). SGD increased the CCI-induced SIRT1 and Ac-NF-κB /NF-κB expression levels in the spinal cord compared with the CCI group, which were reversed by SIRT1-siRNA(i.t)(P〈0.05, P〈0.01). [Conclusion] SGD attenuates behavioral hyperalgesia and allodynia in CCI rats by regulating the expression of SIRT1, which is related to decreasing Ac-NF-κB expression levels in the spinal cord.

关 键 词:神经病理性疼痛(neuropathic pain  NP) 机械痛敏 热痛敏 SIRT1 SIRT1 

分 类 号:R331[医药卫生—人体生理学]

 

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