芍药苷对椎间盘内紊乱兔Fas介导的凋亡通路的调节作用

目的 探讨芍药苷在兔椎间盘内紊乱（internal disc disruption,IDD）发生过程中,是否干预死亡受体介导的信号传导途径,影响髓核细胞的凋亡,及其发生的可能机制.方法 取新西兰大白兔96只,雌雄不限,体重（3.0±0.5） kg.随机分为4组,每组24只.其中3组行纤维环穿刺造模（分别在L3/L4,L4/L及L5/L6椎间盘进行穿刺）.造模后各组分别采用芍药苷高剂量每天120 mg/kg、低剂量每天30 mg/kg及生理盐水灌胃治疗,正常对照组采用生理盐水灌胃,分笼常规饲养.分别在术后的3周、6周和10周将各组大白兔处死取材,每个时间点8只,离断腰椎,分离椎间盘.免疫组化法检测Fas、FasL、Caspase-8的表达,流式细胞术检测细胞凋亡率.结果 造模组Fas、FasL、Caspase-8的表达较正常对照组升高（P＜0.05）.高、低剂量组Fas、FasL、Caspase-8的表达较生理盐水组降低（P＜0.05）.各造模组细胞凋亡率均高于正常对照组（P＜0.05）;高、低剂量组细胞凋亡率低于生理盐水组（P＜0.05）.结论 芍药苷可以抑制Fas表达,进而抑制Caspase-8的激活,最终起到抑制髓核细胞凋亡的作用.

Modulation effect of paeoniflorin for Fas-mediated apoptosis pathway in internal disc disruption rabbit

Objective To investigate the way of paeoniflorin to intervene the death receptor-dependent pathway,and to affect the apoptosis of nucleus pulposus cells.And to investigated the possible pathogenesis.Methods A total of 96 New Zealand white rabbits,male or female,weighed （3.0 ± 0.5） kg were randomly divided into 4 groups and each group has 24.Annulus fibrosus puncture was modeled in 3 groups（puncturing L3/L4,L4/L5 and L5/L6 intervertebral disc）.After modeled,garaging 120 mg/kg paeoniflorin every day （high paeoniflorin group）、30 mg/kg every day （low paeoniflorin group）、saline （saline group and control group）.Each group of white rabbits were sacrificed （n =12） in 3,6,and 10 weeks after surgery.And the discs were harvested.Immunohistochemical study for the expression of Fas,FasL,Caspase-8 in each stage of intervertebral disc tissue.Flow cytometry was used to detect apoptosis rate.Results The expression of Fas,FasL,Caspase-8 in saline group discs were higher than the control group（P 〈 0.05）.The expression of Fas,FasL,Caspase-8 in high and low paeoniflorin groups were lower than the saline group （P 〈 0.05）.The apoptosis rate of the saline group were higher than the control group（P 〈 0.05）,and the high and low paeoniflorin groups were lower than the saline group（P 〈 0.05）.Conclusion Paeoniflorin can inhibit the expression of Fas,thereby inhibiting the activation of Caspase-8,and uhimately restrain the apoptosis of the nucleus.