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吡咯烷二硫代氨基甲酯抑制TNF-α和MMP-9表達延緩大鼠頸椎間盤退變及機制研究

發(fā)布時間:2018-03-04 08:12

  本文選題:吡咯烷二硫代氨基甲酯(PDTC) 切入點:頸椎間盤退變 出處:《中國藥理學(xué)通報》2017年10期  論文類型:期刊論文


【摘要】:目的觀察吡咯烷二硫代氨基甲酯(PDTC)對大鼠頸椎動力失衡模型頸椎間盤組織形態(tài)及腫瘤壞死因子α(TNF-α)、基質(zhì)金屬蛋白酶9(MMP-9)表達的影響,探討PDTC抑制頸椎間盤退變作用及其機制。方法 54只SD大鼠隨機分為3組,切斷大鼠頸后部淺、深肌群構(gòu)建頸椎間盤退變動物模型。PDTC給藥組(A組):造模術(shù)后腹腔每日注射PDTC溶液。模型組(B組):造模術(shù)后腹腔每日注射生理鹽水。假手術(shù)組(C組):手術(shù)切開大鼠頸后部皮膚后立即縫合并每日腹腔注射生理鹽水。術(shù)后10、12、16周分批處死動物,獲取C5/6椎間盤組織,光鏡下觀察椎間盤形態(tài)改變,qPCR檢測椎間盤組織中TNF-αmRNA、MMP-9 mRNA表達;Western blot檢測椎間盤組織中TNF-α、MMP-9蛋白表達變化。結(jié)果 PDTC給藥組(A組)椎間盤結(jié)構(gòu)破壞減輕,纖維環(huán)結(jié)構(gòu)排列有序。模型組(B組)TNF-α、MMP-9基因表達量隨實驗時間的延長而增多,早期增速較快,后期逐漸緩慢,在12周達高峰,而蛋白表達量在術(shù)后10周即達到較高水平,與12周、16周時間點比較無明顯差異(P0.05)。各時間點PDTC給藥組TNF-αmRNA、MMP-9 mRNA及蛋白表達量較模型組(B組)明顯降低(P0.01),但明顯高于假手術(shù)組(P0.01)。結(jié)論 TNF-α、MMP-9是參與大鼠頸椎間盤退變過程的重要炎性因子,TNF-α、MMP-9可能通過NF-κB信號通路參與大鼠頸椎間盤退變,PDTC有望成為頸椎間盤退變的防治藥物。
[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- 偽 mRNA-MMP-9 mRNA in intervertebral disc tissue was detected by qPCR and the expression of TNF- 偽 -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- 偽 MMP-9 gene increased with the prolongation of experimental time. The expression of TNF- 偽 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- 偽 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- 偽 MMP-9 is involved in cervical disc degeneration in rats. TNF- 偽 -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.
【作者單位】: 江西省人民醫(yī)院骨二科;
【基金】:江西省科技支撐計劃資助項目(No 20122BBG70118,20151BBG70119)
【分類號】:R681.5

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