延胡索甲素调节NMDAR/NF-κB介导的信号通路对利血平诱导纤维肌痛大鼠的作用及机制研究

Effect and Mechanism of Corydaline on Reserpine-induced Fibromyalgia in Rats by Regulating NMDAR/NF-κB Mediated Signaling Pathway

目的研究延胡索甲素对利血平诱导纤维肌痛大鼠的作用及机制。方法60只健康雄性SD大鼠随机分为对照组、模型组、延胡索甲素低、中和高剂量组,每组12只。模型组及延胡索甲素低、中、高剂量组皮下注射利血平建立纤维肌痛大鼠模型;造模成功后,延胡索甲素低、中、高剂量组分别给予大鼠5、10、20 mg/ml的延胡索甲素灌胃,对照组及模型组给予生理盐水灌胃,连续给药10 d。计算各组大鼠的体重减轻值和脑组织含水量,并对机械性痛阈值进行测定,检测血浆肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)及IL-1β水平,观察脑组织病理学改变,Western blot检测脑组织NR1、NR2B及核因子-κB(NF-κB)/P65表达水平。结果与对照组比较,模型组痛阈值显著下降,血浆TNF-α、IL-6及IL-1β水平显著升高,脑组织含水量和体重减轻值均显著升高,脑组织NR1、NR2B、NF-κB/P65表达水平显著升高(P<0.05)。与模型组比较,延胡索甲素低、中、高剂量组痛阈值显著升高,血浆TNF-α、IL-6、IL-1β水平显著下降,脑组织含水量和体重减轻值显著降低,脑组织NR1、NR2B、NF-κB/P65表达水平显著降低(P<0.05),且上述指标的变化均呈现出剂量依赖性。模型组脑组织细胞间隙增大,细胞肿胀,细胞核缩小、破裂,核仁不明显;延胡索甲素高、中、低剂量组脑组织细胞破裂凋亡减少,细胞核完整,核仁清晰可见,细胞形态圆润,细胞间隙缩小。结论延胡索甲素能够改善利血平诱导纤维肌痛大鼠的疾病状态,其机制可能与调节N-甲基-D-天冬氨酸受体/NF-κB介导的信号通路有关。

Objective To study the effect of Corydaline on Reserpine-induced fibromyalgia in rats and its mechanism.Methods Sixty healthy male SD rats were randomly divided into control group,model group,low-,moderate-and high-dose Corydaline groups,with 12 rats in each group.The rat model of fibromyalgia was established by subcutaneous injection of Reserpine in the model group and the low-,moderate-and high-dose Corydaline groups.After successful modeling,the rats in the low-,moderate-and high-dose Corydaline groups were given 5,10,and 20 mg/ml Corydaline,respectively,and the control group and model group were given intragastric saline for 10 consecutive days.The weight loss value and brain tissue water content of rats in each group were calculated,and the mechanical pain threshold was measured.The levels of plasma tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-1βwere detected,pathological changes of brain tissue were observed,and western blot was used to detect the expression levels of NR1,NR2B and nuclear factor-κB(NF-κB)/P65 in brain tissues.Results Compared with the control group,the pain threshold of the model group was significantly reduced,and the plasma TNF-α,IL-6 and IL-1βlevels,the brain tissue water content,weight loss values and the expression levels of NR1,NR2B and NF-κB/P65 in brain tissue were significantly increased(P<0.05).Compared with the model group,the pain threshold of the low-,moderate-and high-dose Corydaline groups were significantly increased,while the plasma TNF-α,IL-6 and IL-1βlevels,the brain tissue water content,weight loss values and the expression levels of NR1,NR2B,NF-κB/P65 in brain tissue were significantly reduced(P<0.05),and the changes of the above indicators were in a dose-dependent manner.There was larger space between cells in the brain tissue of the model group,swollen cells,reduced and ruptured nucleus,and unclear nucleolus.The cell rupture and apoptosis of fibromyalgia rats were reduced,with complete nucleus,the nucleolus that was clearly seen,round cell shape was round and reduced cell space in low-,moderate-,high-dose Corydaline groups.Conclusion Corydaline can improve the disease state of Reserpine-induced fibromyalgia in rats,and its mechanism may be related to the regulation of N-methyl-D-aspartate receptors/NF-κB mediated signal pathway.