人参皂苷Rg2对慢性坐骨神经损伤大鼠痛觉敏化和抑郁状态的影响
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摘要
目的:观察人参皂苷Rg2对慢性坐骨神经损伤大鼠痛觉敏化、抑郁状态的影响。方法:将50只SD大鼠随机分为5组(n=10):空白对照组(Normal+生理盐水腹腔注射)、假手术组(手术但不结扎+生理盐水腹腔注射)、坐骨神经慢性压迫损伤(CCI)组(CCI+生理盐水腹腔注射)、人参皂苷Rg2低剂量组(CCI+Rg25 mg/kg腹腔注射)、人参皂苷Rg2高剂量组(CCI+Rg210 mg/kg腹腔注射)。CCI模型建立后,药物通过注射器进行腹腔内注射5ml/kg,每天1次,连续14 d。分别在术前1 d和术后1、3、5、7、10、14 d测定大鼠的机械性缩足反射阈值(MWT)和热缩足潜伏期(TWL);术前1 d和术后第14日时检测明暗箱实验和强迫游泳试验。结果:与假手术组比较,CCI组术后14 d机械痛阈值和热痛潜伏期明显缩短(P<0.01),明箱内停留时间明显缩短(P<0.01),穿梭次数明显减少(P<0.01),游泳潜伏期明显延长(P<0.01)。与CCI组比较,人参皂苷Rg2组术后14 d机械痛阈和热痛潜伏期明显增加(P<0.01),大鼠在明箱内时间明显延长(P<0.01),穿梭次数明显增多(P<0.01),且游泳潜伏期明显缩短(P<0.01)。结论:人参皂苷Rg2能抑制CCI大鼠的机械痛敏和热痛敏,同时改善其抑郁状态。
Objective: To investigate the effects of ginsenoside-Rg2 on mechanical allodynia,heat hyperalgeia,depressive state of rats with chronic sciatic nerve constriction injury. Methods: Fifty SD rats were randomly divided into 5 groups: blank control group( Normal,normal + saline),sham operation group( Sham,sham operation + saline),chronic constriction injury of the sciatic nerve group( CCI,CCI + saline),ginsenoside-Rg2 low dose group( CCI + Rg25 mg/kg),and ginsenoside-Rg2 high dose group( CCI + Rg210 mg/kg).After the CCI model was established,drug were injected into the abdominal cavity through the syringe once a day,for 14 consecutive days.The mechanical shrinkage foot reflex threshold( MWT) and thermal withdrawal latency( TWL) were determined at 1 d before the operation and at 1,3,5,7,10 and 14 d after the operation.Light-dark transition test,forced swimming test were determined at1 d before the operation and at 14 d after the operation.Results: Compared with the sham group,the MWL and TWL of the CCI rats were decreased significantly( P<0.01),time in the light compartment and number of transition were decreased( P<0.01),the immobility time in FST was also prolonged significantly( P<0.01). At 14 days after CCI operation,the MWL and TWL of the ginsenosideRg2 groups were increased significantly( P<0.01),time in the light compartment and number of transition were also shortened significantly( P<0.01),the immobility time in FST was also shortened significantly( P<0.01). Conclusion: Intraperitoneal injection of ginsenoside-Rg2 can inhibit the mechanical and thermal pain sensitivity of CCI rats,and can relieve depressive state.
Objective: To investigate the effects of ginsenoside-Rg2 on mechanical allodynia,heat hyperalgeia,depressive state of rats with chronic sciatic nerve constriction injury. Methods: Fifty SD rats were randomly divided into 5 groups: blank control group( Normal,normal + saline),sham operation group( Sham,sham operation + saline),chronic constriction injury of the sciatic nerve group( CCI,CCI + saline),ginsenoside-Rg2 low dose group( CCI + Rg25 mg/kg),and ginsenoside-Rg2 high dose group( CCI + Rg210 mg/kg).After the CCI model was established,drug were injected into the abdominal cavity through the syringe once a day,for 14 consecutive days.The mechanical shrinkage foot reflex threshold( MWT) and thermal withdrawal latency( TWL) were determined at 1 d before the operation and at 1,3,5,7,10 and 14 d after the operation.Light-dark transition test,forced swimming test were determined at1 d before the operation and at 14 d after the operation.Results: Compared with the sham group,the MWL and TWL of the CCI rats were decreased significantly( P<0.01),time in the light compartment and number of transition were decreased( P<0.01),the immobility time in FST was also prolonged significantly( P<0.01). At 14 days after CCI operation,the MWL and TWL of the ginsenosideRg2 groups were increased significantly( P<0.01),time in the light compartment and number of transition were also shortened significantly( P<0.01),the immobility time in FST was also shortened significantly( P<0.01). Conclusion: Intraperitoneal injection of ginsenoside-Rg2 can inhibit the mechanical and thermal pain sensitivity of CCI rats,and can relieve depressive state.
引文
[1]付波,翁谢川,王静,等.慢性神经痛对抑郁状态以及中枢多巴胺神经元电生理的影响[J].中国应用生理学杂志,2016,32(5):403-407.
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[9]张娟,马千,吕晨,等.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[J].浙江中医药大学学报,2015,39(5):329-334.
[10]Zhang M,Dai W,Liang J,et al.Effects of UCMS-induced depression on nociceptive behaviors induced by electrical stimulation of the dura mater[J].Neurosci Lett,2013,551:1-6.
[11]徐静,鲁玉刚,俞卫锋.慢性坐骨神经结扎大鼠前扣带皮层对脊髓痛觉信息传递的调节[J].临床麻醉学杂志,2016,32(4):393-397.
[12]Li TT,Ren WH,Xiao X,et al.NMDA NR2A and NR2Breceptors in the rostral anterior cingulated cortex contribute to pain-related aversion in male rats[J].Pain,2009,146(1-2):183-193.
[13]Ren Y,Wang JL,Zhang X,et al.Antidepressant-like effects of ginsenoside Rg2 in a chronic mild stress model of depression[J].Brain Res Bull,2017(134):211-219.
[14]Herskovits AZ,Guarente L.SIRT1 in neurodevelopment and brain senescence[J].Neuron,2014,81(3):471-483.
[15]Bennett GJ,Doyle T,Salvement D.Mitotoxicity in distal symmetrical sensory peripheral neuropathies[J].Nat Rev Neurol,2014,10(6):326-336.
[2]刘茹,谢泽敏,王星明,等.丰富环境对坐骨神经慢性压迫小鼠痛阈及抑郁样行为的影响[J].临床麻醉学杂志,2018,34(1):57-62.
[3]Yalcin I,Barthas F,Barrot M.Emotional consequences of neuropathic pain:insight from preclinical studies[J].Neurosci Biobehav Rev,2014,47:154-164.
[4]胡玲,王星明,杨建军.慢性疼痛导致抑郁症的相关机制[J].江苏医药,2012,38(16):1936-1938.
[5]马赫佟,郜玉钢,祝洪艳,等.人参皂苷Rg2、Rh1对神经系统作用及相关机制的研究进展[J].上海中医药杂志,2018,52(12):110-112.
[6]吕晨,郭小文,郑晖,等.腹腔注射SRT1720对慢性坐骨神经结扎大鼠痛觉敏化和脊髓Sirt1表达/活性的影响[J].中华全科医学,2016,14(6):900-903.
[7]朱雅冰,贾改丽,陆嘉辉,等.脊髓自噬功能激活与大鼠2型糖尿病神经病理性疼痛的关系[J].中国应用生理学杂志,2018,34(4):318-323.
[8]马益梅,李传达,朱雅冰,等.Rv D1对大鼠2型糖尿病神经病理性痛的作用及机制研究[J].中国应用生理学杂志,2017,33(3):277-281.
[9]张娟,马千,吕晨,等.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[J].浙江中医药大学学报,2015,39(5):329-334.
[10]Zhang M,Dai W,Liang J,et al.Effects of UCMS-induced depression on nociceptive behaviors induced by electrical stimulation of the dura mater[J].Neurosci Lett,2013,551:1-6.
[11]徐静,鲁玉刚,俞卫锋.慢性坐骨神经结扎大鼠前扣带皮层对脊髓痛觉信息传递的调节[J].临床麻醉学杂志,2016,32(4):393-397.
[12]Li TT,Ren WH,Xiao X,et al.NMDA NR2A and NR2Breceptors in the rostral anterior cingulated cortex contribute to pain-related aversion in male rats[J].Pain,2009,146(1-2):183-193.
[13]Ren Y,Wang JL,Zhang X,et al.Antidepressant-like effects of ginsenoside Rg2 in a chronic mild stress model of depression[J].Brain Res Bull,2017(134):211-219.
[14]Herskovits AZ,Guarente L.SIRT1 in neurodevelopment and brain senescence[J].Neuron,2014,81(3):471-483.
[15]Bennett GJ,Doyle T,Salvement D.Mitotoxicity in distal symmetrical sensory peripheral neuropathies[J].Nat Rev Neurol,2014,10(6):326-336.