淫羊藿苷改善大鼠坐骨神经慢性压迫损伤的作用与机制

Improving effect and mechanism of icariin on chronic constriction injury in rats

目的探讨淫羊藿苷(Ica)对坐骨神经慢性压迫损伤(CCI)的改善作用及可能机制。方法45只SD大鼠结扎坐骨神经,建立CCI模型,随机分为模型组、Ica(30 mg·kg^(-1))组、Ica+溶血磷脂酸(LPA,1 mg·kg^(-1))组,另设假手术组。相应干预2周后,测定机械性缩足反射阈值(PWMT)、热刺激缩足反射潜伏期(PWTL),并通过明暗箱实验检测大鼠行为学变化,紫外比色法检测前扣带回皮质(ACC)谷氨酸含量,电压膜片钳检测微小兴奋性突触后电流(mE PSC)频率和幅度,Western blot法检测ACC中c-Fos、哺乳动物雷帕霉素靶蛋白(mTOR)、p-mTOR、p70核糖体蛋白S6激酶(p70S6K)、p-p70S6K蛋白表达。结果与假手术组比较,模型组PWMT下降,PWTL、明箱活动时间缩短,穿梭次数减少,ACC中谷氨酸含量、c-Fos、p-mTOR、p-p70S6K蛋白表达增加(P<0.05)。与模型组比较,Ica组和Ica+LPA组PWMT升高,PWTL、明箱活动时间延长,穿梭次数增加,ACC中谷氨酸含量、c-Fos、p-mTOR、p-p70S6K蛋白表达减少(P<0.05)。与Ica组比较,Ica+LPA组PWMT下降,PWTL、明箱活动时间缩短,穿梭次数减少,ACC中谷氨酸含量、c-Fos、p-mTOR、p-p70S6K蛋白表达增加(P<0.05)。结论Ica可减轻CCI大鼠痛觉过敏和情绪障碍,改善ACC突触可塑性,降低其兴奋性,其机制可能与抑制mT OR信号通路有关。

AIM To investigate the effect of icariin(Ica)on rats with chronic constriction injury(CCI)of the sciatic nerve and its possible mechanism.METHODS Forty-five SD rats were ligated to the sciatic nerve to establish a CCI model.The rats were randomly divided into model group,Ica(30 mg·kg^(-1))group,Ica+lysophosphatidic acid(LPA,1 mg·kg^(-1))group.In addition,a sham operation group was set up.After corresponding intervention for 2 weeks,the paw withdrawal mechanical threshold(PWMT)and the paw withdrawal thermal latency(PWTL),light and dark box experiment were used to detect changes in rat behavior.The glutamate content in anterior cingulate cortex(ACC)was detected by UVcolorimetry.The frequency and amplitude of miniature excitatory postsynaptic current(mEPSC)were detected by voltage patch clamp.And the protein expression of c-Fos,mammalian target of rapamycin(mTOR),p-mTOR,p70 ribosomal protein S6 kinase(p70S6K),and p-p70S6K in ACC were detected by Western blot.RESULTS Compared with the sham operation group,PWMT decreased,PWTL and light box activity time shortened,the number of shuttles decreased,the glutamate content and the protein expression of c-Fos,p-mTOR,p-p70S6K in ACC increased in the model group(P<0.05).Compared with the model group,PWMT increased,PWTL and light box activity time prolonged,the number of shuttles increased,the glutamate content and the protein expression of c-Fos,p-mTOR,p-p70S6K in ACC decreased in the Ica group(P<0.05).Compared with the Ica group,PWMT decreased,PWTL and light box activity time shortened,shuttle times decreased,ACCglutamate content and the protein expression of c-Fos,p-mTOR,p-p70S6K increased in the Ica+LPA group(P<0.05).CONCLUSION Ica can alleviate hyperalgesia and mood disorders in CCI rats,improve the synaptic plasticity of ACC,and reduce its excitability.The mechanism may be related to the inhibition of mTOR signaling pathway.