吡咯烷二硫代氨基甲酯抑制TNF-α和MMP-9表达延缓大鼠颈椎间盘退变及机制研究

发布时间：2018-03-04 08:12

本文选题：吡咯烷二硫代氨基甲酯(PDTC)　切入点：颈椎间盘退变　出处：《中国药理学通报》2017年10期 　论文类型：期刊论文

【摘要】：目的观察吡咯烷二硫代氨基甲酯(PDTC)对大鼠颈椎动力失衡模型颈椎间盘组织形态及肿瘤坏死因子α(TNF-α)、基质金属蛋白酶9(MMP-9)表达的影响,探讨PDTC抑制颈椎间盘退变作用及其机制。方法 54只SD大鼠随机分为3组,切断大鼠颈后部浅、深肌群构建颈椎间盘退变动物模型。PDTC给药组(A组):造模术后腹腔每日注射PDTC溶液。模型组(B组):造模术后腹腔每日注射生理盐水。假手术组(C组):手术切开大鼠颈后部皮肤后立即缝合并每日腹腔注射生理盐水。术后10、12、16周分批处死动物,获取C5/6椎间盘组织,光镜下观察椎间盘形态改变,qPCR检测椎间盘组织中TNF-αmRNA、MMP-9 mRNA表达;Western blot检测椎间盘组织中TNF-α、MMP-9蛋白表达变化。结果 PDTC给药组(A组)椎间盘结构破坏减轻,纤维环结构排列有序。模型组(B组)TNF-α、MMP-9基因表达量随实验时间的延长而增多,早期增速较快,后期逐渐缓慢,在12周达高峰,而蛋白表达量在术后10周即达到较高水平,与12周、16周时间点比较无明显差异(P0.05)。各时间点PDTC给药组TNF-αmRNA、MMP-9 mRNA及蛋白表达量较模型组(B组)明显降低(P0.01),但明显高于假手术组(P0.01)。结论 TNF-α、MMP-9是参与大鼠颈椎间盘退变过程的重要炎性因子,TNF-α、MMP-9可能通过NF-κB信号通路参与大鼠颈椎间盘退变,PDTC有望成为颈椎间盘退变的防治药物。
[Abstract]:Objective to observe the effect of pyrrolidine dithiocarbamate (PDTCN) on the morphology of cervical intervertebral disc and the expression of matrix metalloproteinase 9 (MMP-9) in cervical disc of rats with cervical dynamic imbalance. To investigate the inhibitory effect of PDTC on cervical disc degeneration and its mechanism, 54 SD rats were randomly divided into 3 groups. Animal model of cervical intervertebral disc degeneration. Group A: intraperitoneal injection of PDTC solution daily after modeling. Group B: intraperitoneal injection of normal saline daily after modeling. The skin of the posterior part of the neck was sutured immediately and intraperitoneally injected with saline daily. The animals were executed in batches 10 weeks and 1216 weeks after operation. C5 / 6 intervertebral disc tissue was obtained. The morphological changes of intervertebral disc were observed under light microscope. The expression of TNF- 伪 mRNA-MMP-9 mRNA in intervertebral disc tissue was detected by qPCR and the expression of TNF- 伪 -mRNA-MMP-9 protein in intervertebral disc tissue was detected by Western blot. Results the structural damage of intervertebral disc was alleviated in group A (treated with PDTC). In group B, the expression of TNF- 伪 MMP-9 gene increased with the prolongation of experimental time. The expression of TNF- 伪 MMP-9 gene increased rapidly in the early stage, slowly in the later stage, and reached its peak at 12 weeks, while the protein expression reached a higher level at 10 weeks after operation. TNF- 伪 mRNA-MMP-9 mRNA and protein expression in PDTC group were significantly lower than those in model group B (P 0.01), but significantly higher than that in sham operation group (P 0.01). Conclusion TNF- 伪 MMP-9 is involved in cervical disc degeneration in rats. TNF- 伪 -MMP-9 may be involved in the degeneration of rat cervical intervertebral disc through NF- 魏 B signaling pathway, and PDTC may be a drug to prevent and treat the degeneration of cervical intervertebral disc.
【作者单位】：江西省人民医院骨二科;
【基金】：江西省科技支撑计划资助项目(No 20122BBG70118,20151BBG70119)
【分类号】：R681.5

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