【摘要】 目的:探索橙皮素(HES)对坐骨神经压迫性损伤(PSNL)模型大鼠的镇痛作用及相关分子机制。方法:制作大鼠PSNL模型。75只大鼠随机分为5组,15只/组,分别为假手术(sham)组、模型(model)组、HES低浓度(HES 10)组、HES中浓度(HES 20)组和HES高浓度(HES 40)组,分别给与HES 10 mg/kg、20 mg/kg、40 mg/kg灌胃给药,1次/日,连续21 d,sham组和model组给与等量生理盐水灌胃。分别于术前1 d和术后1、7、14、21 d测定大鼠后足热缩足反射潜伏期(TWL)及机械缩足反射阈值(MWT);第21天取各组大鼠右侧坐骨神经,Elisa法检测氧化应激因子一氧化氮(NO)、炎症因子肿瘤坏死因子(TNF)-α、白介素(IL)-1β、IL-6和单核细胞趋化因子(MCP)-1含量和内皮型一氧化氮合酶(e NOS)活性;Western blot法检测e NOS蛋白表达水平,免疫组化法检测TNF-α、IL-1β的表达。结果:造模后TWL和MWT显著下降(P<0.05),HES治疗7、14、21 d后TWL及MWT明显升高,高于model组(P<0.05)。Elisa结果显示,造模后,NO、TNF-α、IL-1β、IL-6、MCP-1含量及e NOS活性显著提高(P<0.05);HES治疗21 d后,NO、TNF-α、IL-1β、IL-6、MCP-1含量和e NOS活性明显降低,低于model组(P<0.05)。Western结果显示,造模后,e NOS蛋白表达显著提高,HES可显著抑制e NOS蛋白表达,低于model组(P<0.05)。免疫组化检测结果显示,HES治疗21 d后,TNF-α和IL-1β均显著低于model组(P<0.05)。结论:HES能缓解坐骨神经结扎引起的神经病理性疼痛,其分子机制可能与抑制坐骨神经氧化应激反应和炎症反应有关。更多还原

【Abstract】 Objective: To investigate the effects Hesperetin(HES) on relieving pain and the expression of oxidative stress factors and inflammatory factors in partial sciatic nerve ligation(PSNL) model rats. Methods: Seventy-five SD rats were randomly divided into five groups(n=15 respectively): sham group, model group, HES 10group(10 mg/kg), HES 20 group(20 mg/kg) and HES 40 group(40 mg/kg). Thermal withdrawal latency(TWL)and mechanical withdrawal threshold(MWT) were tested 1 day before and 1, 7, 14, 21 days after surgery. Twenty-one days after surgery, the rats were harvested. The content of nitric oxide(NO), tumor necrosis factor(TNF)-α, interleukin(IL)-1β, IL-6, monocyte chemotactic factor(MCP)-1 and the activity of endothelial nitric oxide synthase(e NOS) were detected by Elisa. The protein expression of e NOS was valued by western blot method and the protein expression of TNF-α and IL-1β were observed via immunohistochemical staining. Results:Compared with those in the sham group, TWL and MWT in model group were significantly down-regulated(P<0.05). While 7, 14, 21 days after HES treatment, TWL and MWT in HES group were markedly up-regulated compared with those in the model group(P<0.05). Data of Elisa showed that the content of NO, TNF-α, IL-1β, IL-6,MCP-1 and the activity of e NOS increased in model group(P<0.05), which were significantly decreased after 21-day treatment of HES(P<0.05). Data of western blot showed that the HES treatment significantly suppressed the protein expression of e NOS(P<0.05). Data of immunohistochemical staining showed that HES treatment significantly suppressed the protein expression of TNF-α and IL-1β(P<0.05). Conclusion: HES can relieve the neuropathic pain induced by sciatic nerve ligation, and the molecular mechanism may be related to the anti-oxidative stress and anti-inflammation.更多还原