芍药苷可逆转疼痛共病抑郁大鼠海马内脑源性神经营养因子含量的减少

Paeoniflorin Reversed Reduction of BDNF in Hippocampus of Pain-Comorbidity Depression Rats

目的观察慢性压迫性损伤(CCI)和慢性轻度应激(CMS)共患大鼠热痛阈及机械痛阈的变化,并研究芍药苷对CCI+CMS大鼠海马内脑源性神经营养因子(rain-derived neurotrophic factor,BDNF)表达的影响。方法分别用机械缩足反射阈值(MWT)和热缩足潜伏期(TWL)来评价大鼠机械痛敏和热痛敏。用敞箱实验中的总路程、中心格路程及穿越中心格次数来评价大鼠的抑郁样状态。SD大鼠随机分为6组:Sham组(假手术组)、CCI组、CCI+CMS+NS组、CMS组、CCI+CMS+芍小组(芍药苷低剂量组50 mg/kg),CCI+CMS+芍大组(芍药苷高剂量组100 mg/kg)。各组分别在术前1 d和术后7 d、14 d测定MWT和TWL,术后14 d行敞箱实验,最后提取大鼠海马测定BDNF的蛋白表达。结果和Sham组相比,CCI组及CCI+CMS+NS组在术后7 d、14 d的PWL、MWT均降低(P<0.05),且CCI+CMS+NS组PWL、MWT降低更为显著。芍药苷组可逆转CCI+CMS+NS组的热痛敏和机械痛敏。芍大及芍小组在逆转热痛敏上有显著差异(P<0.05),在逆转机械痛敏上无显著差异。和Sham组相比,CMS组及CCI+CMS+NS组的总路程、中心格总路程、穿越中心格次数均减少(P<0.05),且CCI+CMS+NS组减少的更为显著。芍药苷组可逆转CCI+CMS+NS组大鼠总路程、中心格总路程及穿越中心格次数的减少,即逆转抑郁样行为,但芍大及芍小组仅在总路程的减少上有差异(P<0.05),另两项指标无差异。和Sham组相比,CMS组、CCI+CMS+NS组海马内BDNF含量减少(P<0.05),且CCI+CMS+NS组减少的更为显著。芍药苷组可逆转CCI+CMS+NS组BDNF含量的减少,但芍大与芍小组无显著差异。结论芍药苷能抑制CCI+CMS大鼠的机械痛敏和热痛敏,逆转抑郁样行为,同时高剂量组较低剂量组效果更为显著,其抗抑郁及镇痛作用机制可能和增加海马内BDNF的表达有关。

Objective To observe the changes of heat pain threshold and mechanical pain threshold in chronic compression injury(CCI)and chronic mild stress(CMS)co-affected rats and investigate the effect of paeonin on the expression of brain derived neurotrophic factor(BDNF)in the hippocampus of CCI+CMS rats.Methods Mechanical and thermal pain sensitivity were evaluated by mechanical foot reflex threshold(MWT)and thermal foot latency(TWL),respectively.The depression-like state of the rats was evaluated by the total distance,the distance of the central lattice and the times of crossing the central lattice in the open-box experiment.SD rats were randomly divided into 6 groups:sham group(sham operation group),CCI group,CCI+CMS+NS group,CMS group,CCI+CMS+paeoniflorin low-dose group(50 mg/kg)and CCI+CMS+paeoniflorin high-dose group(100 mg/kg).MWT and TWL were measured 1 d before and 7 d and 14 d after surgery,respectively.After surgery,the hippocampus of rats was extracted to measure the protein expression of BDNF.Results Compared with those of the sham group,the PWL and MWT of CCI group and CCI+CMS+NS group were decreased 7 and 14 days after surgery(P<0.05),and the decrease of PWL and MWT of CCI+CMS group was more significant.Paeoniflorin groups could reverse the heat and mechanical pain sensitivity of CCI+CMS+NS group.There was significant difference between paeoniflorin low-dose group and paeoniflorin high-dose group group in the reverse heat pain sensitivity(P<0.05),but no significant difference in the reverse mechanical pain sensitivity.Compared with those of the sham group,the total distance,the total distance of center grid and the times of crossing center grid in CMS group and CCI+CMS+NS group were all reduced(P<0.05),and the reduction in CCI+CMS+NS group was more significant.Paeoniflorin groups could reverse the reduction of total distance,total distance of center grid and the number of crossing center grid in CCI+CMS+NS group,that is,the depression like behavior was reversed,but only the reduction of total distance was different in the paeoniflorin low-dose group group and paeoniflorin high-dose group group(P<0.05),the other two indexes were not different.Compared with that of the sham group,BDNF content in the hippocampus of CMS group and CCI+CMS+NS group decreased(P<0.05),and the decrease in CCI+CMS+NS group was more significant.Paeoniflorin groups could reverse the reduction of BDNF content in CCI+CMS+NS group,but there was no significant difference between paeoniflorin low-dose group and paeoniflorin high-dose group.Conclusion Paeoniflorin can inhibit mechanical pain sensitivity and heat pain sensitivity and reverse depressive behavior in CCI+CMS rats,and the effect in high-dose group is more significant than that in low-dose group.Moreover,the mechanism of antidepressant and analgesia may be related to the increase of BDNF expression in hippocampus.