芒果苷对神经病理性大鼠坐骨神经的保护作用

Protective Effects of Mangiferin on Partial Sciatic Nerve of Neuropathic Rats

目的:探讨芒果苷(MGF)对坐骨神经压迫性损伤模型(PSNL)大鼠的镇痛作用及相关的分子机制研究。方法:60只大鼠随机分为假手术组、模型组、MGF 25 mg/kg组、MGF 50 mg/kg组和MGF 100 mg/kg组,分别于术后1 d、10 d、20 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20 d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)含量和内皮型一氧化氮合酶(e NOS)活性,以及氧化应激因子丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH)、过氧化氢酶(CAT)含量,Western blotting法检测e NOS蛋白表达水平。结果:第1 d、10 d和20 d,模型组较假手术组TWL[(13.1±1.2)vs(6.7±0.8),(13.6±1.3)vs(6.9±0.7),(13.7±1.3)vs(6.8±0.9)]和MWT[(43.6±3.9)vs(35.2±3.7),(44.2±4.1)vs(35.4±3.8),(44.5±4.9)vs(35.6±3.7)]显著下降;术后第1 d,模型组与各浓度MGF组之间无显著差异,而第10 d和20 d,MGF各浓度组较模型组TWL和MWT明显提高;ELISA结果显示,术后20 d MGF各浓度组较模型组MDA含量显著降低,并且MGF各浓度组较模型组SOD、GSH和CAT含量显著提高,MGF 25 mg/kg组、MGF 50 mg/kg组和MGF 100 mg/kg组NO含量[(40.2±3.9)、(33.6±3.4)、(29.9±3.1)ng/mg]和e NOS活性[(105.7±5.3)、(89.3±4.7)、(0.2±5.1)μmol/g]较模型组[(58.9±4.3)ng/mg、(148.2±6.9)μmol/g]显著下降(P<0.05);Western blotting结果显示,MGF 25 mg/kg组、MGF 50 mg/kg组和MGF 100 mg/kg组可显著抑制e NOS活性[(17.1±1.3)、(14.2±1.1)、(12.8±1.3)],与模型组(22.6±2.8)比较有统计学意义(P<0.05)。结论:芒果苷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有关。

Objective To investigate the analgesic effect of mangiferin （MGF） on sciatic nerve in rats with neuropathic pain and to explore the potential mechanism. Methods Sixty rats were randomly divided into ？ve groups： Sham group, model group, MGF 25 mg/kg group, MGF 50 mg/kg group and MGF 100 mg/kg group. Thermal withdrawal latency （TWL） and mechanical withdrawal threshold （MWT） were detected before surgery and on day 1, 10 and 20 after surgery. The content of nitric oxide （NO） and the activity of endothelial nitric oxide synthase （eNOS） were detected by ELISA, the levels of malondialdehyde （MDA）, superoxide dismutase （SOD）, glutathione peroxidase （GSH） and catalase （CAT） were also detected on day 20 after surgery, and eNOS protein expression was valued by Western blotting. Results On day 1, day10 and day20, TWL and MWT in model group were signi？cantly down-regulated, compared with Sham group [（13.1±1.2） vs （6.7±0.8）, （13.6±1.3） vs （6.9±0.7）, （13.7±1.3） vs （6.8±0.9）, P 〈 0.05], [（43.6±3.9） vs （35.2±3.7）, （44.2±4.1） vs （35.4±3.8）, （44.5±4.9） vs （35.6±3.7）, P 〈 0.05]. There was no significant difference in TWL and MWT between the MGF group and model group on day 1, while TWL and MWT in MGF 25 mg/kg group, MGF 50 mg/kg group and MGF 100 mg/kg group were markedly up-regulated on day 10 and day 20. ELISA results demonstrated that the content of MDA in MGF group was signi？cantly down-regulated, and the contents of SOD, GSH and CAT in MGF groups were markedly up-regulated, compared with the model group. Besides, the NO contents [（40.2±3.9）,（33.6±3.4） and （29.9±3.1） ng/mg] and the eNOS activities [（105.7±5.3）, （89.3±4.7） and （80.2±5.1） μmol/g] in MGF 25 mg/kg, 50 mg/kgand 100 mg/kg groups were signi？cantly down-regulated, compared with the model group [（58.9±4.3） ng/mg and （148.2±6.9） μmol/g, P 〈 0.05]. Western blotting indicated that the protein expression of eNOS in MGF group [（17.1±1.3）, （14.2±1.1） and （12.8±1.3）] was markedly down-regulated, compared with the model group （22.6±2.8）. Conclusion MGF can relieve the neuropathic pain induced by sciatic nerve ligation, and the molecular mechanism may be related to the anti-oxidative stress and anti-in？ammation.