近年來,國內外的學者對椎間盤的生物化學變化進行了大量深入的研究,對揭示椎間盤退變規(guī)律作出了很多貢獻。但是,對椎間盤退變機制的解釋尚不圓滿,很多問題還有待于解決。目前這種狀況還不能適應椎間盤疾病防治工作的需要。展望未來,椎間盤生物化學研究有望從以下幾個方面獲得突破性進展。
1.椎間盤細胞的生物學特性研究 椎間盤主要由細胞及周圍基質構成,通過探討細胞生長、繁殖、凋亡的規(guī)律,有助于深入了解椎間盤基質生化成分的代謝特點,探索椎間盤生物化學的變化規(guī)律,有助于尋找預防椎間盤退變的方法,對預防與治療退變性疾病具有重要意義。
2.膠原與蛋白多糖調控機制的研究 隨著對椎間盤基質成分結構、功能以及調節(jié)規(guī)律認識的逐步深入,用各種手段調節(jié)不同退變時期椎間盤內基質成分的種類和水平,利用不同基質成分及合成類抑制因子調節(jié)其活性可以從根本上調控椎間盤基質成分的含量與性質變化,改善椎間盤力學性能,從而達到預防或延緩椎間盤退變的目的。膠原和蛋白多糖作為椎間盤組織中的主要大分子物質,在椎間盤中具有極其重要的功能,對其結構和功能的進一步研究,將為椎間盤的退變的預防和椎間盤突出的治療開拓一種新的途徑。如對膠原與蛋白多糖基因的監(jiān)測、蛋白多糖基因的體內轉染等,在椎間盤疾病的預防和治療方面都具有較高的研究價值和較好的應用前景。
3.椎間盤基質降解機制的研究 近年來,認為在椎間盤退變過程中,基質金屬蛋白酶(MMPs)發(fā)揮著重要作用,但是到目前為止僅僅在椎間盤中發(fā)現(xiàn)幾種MMPs,隨著現(xiàn)代檢測技術的進步,如免疫細胞化學、原位雜交技術、酶譜學等的應用,無疑將使我們能夠在椎間盤中發(fā)現(xiàn)更多的MMPs,通過建立更接近于體內環(huán)境的培養(yǎng)體系,以觀察各種因子對MMPs的影響,探討MMPs的作用和調節(jié)機制,采用基因治療策略,調控椎間盤中MMPs的表達,通過對MMPs降解基質成分及其調控機制研究,可尋找到阻止椎間盤退變的有效方法。在應用基質降解酶進行化學溶核療法的基礎和臨床研究時,在觀察它們對髓核作用的同時,進一步明確其對軟骨終板、纖維環(huán)的作用特點,對神經組織的急慢性毒性反應以及硬膜外和椎間盤內注射引起的近、遠期并發(fā)癥等,對這些問題的正確認識和深入探討將會使化學溶核療法成為一種治療椎間盤突出癥真正有價值的方法。
4.組織工程和細胞生物學的研究與基因治療椎間盤退變 近年來,組織工程和細胞生物學的研究取得突破性進展,從椎間盤的生物化學領域,用各種手段調節(jié)不同退變時期椎間盤內基質成分的種類和水平,利用基因調節(jié)其活性可以從根本上調控椎間盤基質成分的含量與性質變化。在椎間盤退變過程中,基質成分變化對椎間盤的生理功能產生較大的影響。基因治療的主要方法應該是利用基因轉染技術,使體細胞表達對椎間盤退變有抑制和逆轉作用的生長因子,預防或延緩椎間盤退變,使椎間盤基質成分的產生變化。基因治療中存在的缺點和不足,如生物安全性、表達穩(wěn)定性差等,是基因治療椎間盤退變需要解決的問題?;蛑委熓墙窈笾委熥甸g盤退變的重要方向。
(楊華清)
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