脂氧素A4缓解非压迫性腰椎间盘突出症模型大鼠根性神经痛的作用机制

Mechanism of lipoxin A4 in alleviating radicular neuralgia in rat model with non-compression lumbar disc herniation

目的探讨脂氧素A4缓解非压迫性腰椎间盘突出症模型大鼠根性神经痛的作用机制。方法雄性SD大鼠48只随机均分为四组。S组仅暴露相应手术操作部位,术后连续3 d鞘内注射生理盐水10μL/d。M、A和B组建立非压迫性腰椎间盘突出症模型后,分别连续3 d鞘内注射生理盐水10μL/d、含脂氧素A410 ng/d和脂氧素A4100 ng/d的生理盐水10μL/d。比较四组术前1 d和术后7 d的大鼠右侧后肢50%缩足反射阈值(PWT)。RT-PCR法和Western blot法分别检测术后第7天四组大鼠右侧L_(4)~L_(6)段脊髓背角组织炎症因子mRNA表达和NF-κB/p65蛋白表达。结果与S组比较,M、A、B组术后各时间点50%PWT均降低(P<0.05)。与M组比较,A组和B组术后各时间点50%PWT升高,且B组升高更明显(P<0.05)。与S组比较,M、A、B组TNF-α、IL-1βmRNA表达和NF-κB/p65蛋白表达升高,而转化生长因子β1(TGF-β1)mRNA表达降低(P<0.05)。与M组比较,A组和B组TNF-α、IL-1βmRNA表达和NF-κB/p65蛋白表达降低,而TGF-β1 mRNA表达升高,且B组变化更明显(P<0.05)。结论脂氧素A4可以缓解非压迫性腰椎间盘突出症模型大鼠根性神经痛,其作用机制可能与调节炎症介质表达和抑制NF-κB/p65活性有关。

Objective To investigate the mechanism of lipoxin A4 in alleviating radicular neuralgia in rat model with non-compression lumbar disc herniation.Methods Forty-eight male SD rats were randomly and equally divided into four groups.The rats in group S were treated with exposing the corresponding operation site only,which were injected intrathecally with normal saline 10μL/d for 3 days after surgery.A model of non-compression lumbar disc herniation was established in groups of M,A and B,which then was injected intrathecally with normal saline 1oμL/d,normal saline 10μL/d with lipoxin A410 ng/d and lipoxin A4100 ng/d for 3 days,respectively.The 50%paw withdrawal threshold(PWT)of the right hind limb was recorded at one day before and within 7 days after surgery in the four groups.The expressions of inflammatory factors mRNA and NF-kB/p65 protein in dorsal horn of the right spinal cord at the 7^(th )day after surgery in four groups were detected by RT-PCR and Western blot,respectively.Results Compared with group S,50%PWT in groups of M,A and B was decreased at each time point after surgery(P<0.05).Compared with group M,50%PWT in groups of A and B was increased at each time point after surgery,and the increase in group B was more obvious(P<0.05).Compared with group S,mRNA expressions of TNF-αand IL-1β,and NF-sB/p65 protein expression were increased in groups of M,A and B,while mRNA expressions of transforming growth factorβ1(TGF-β1)were decreased(P<0.05).Compared with group M,mRNA expressions of TNF-αand IL-1βand NF-B/p65 protein expression were decreased,while mRNA expression of TGF-pl was increased in groups of A and B,and the changes were more in group B(P<0.05).Conclusion Lipoxin A4 can relieve radicular neuralgia in rat model with non-compression lumbar disc herniation,and its mechanism may be related to regulating expression of inflammatory mediators and inhibiting activity of NF-B/p65.