【摘要】 目的:探讨一氧化氮合酶(nitricoxidesynthase,NOS)抑制剂S-甲基异硫脲(S-methylisothiourea,SMT)对退行性变腰椎间盘基质代谢的影响,为NOS抑制剂的临床应用提供理论依据。方法:实验于2003-03/2004-01在卫生部小儿先天畸形重点实验室完成。无菌条件下,取20例腰椎间盘突出症患者的椎间盘组织(髓核和纤维环),置入体外培养系统,随机分为对照组:不加药物干预;SMT组:加入1mmol/LSMT干预。培养72h后,通过检测硝酸盐和亚硝酸盐的含量来观察椎间盘组织一氧化氮的释放量及NOS的活性;原位杂交法检测椎间盘组织诱导型一氧化氮合酶(induciblenitricoxidesynthase,iNOS)mRNA和基质金属蛋白酶(matrixmetalloprotease,MMP3)mRNA的表达。培养10d后,化学比色法观察椎间盘蛋白多糖含量和羟脯氨酸释放量的变化。结果:SMT组髓核和纤维环一氧化氮释放量较对照组明显减少,NOS活性明显降低(P<0.01)。培养10d后,SMT组髓核组织中蛋白多糖含量比对照组明显增加(t=8.52,P<0.01),羟脯氨酸释放量比对照组显著减少(t=6.58,P<0.01);同时,未检测到iNOSmRNA和MMP3mRNA的表达。结论:NOS抑制剂SMT能抑制过量一氧化氮的释放,对延缓椎间盘退行性变具有积极的作用。更多还原

【Abstract】 AIM:To investigate the effects of nitric oxide synthase(NOS) inhibitor, S methylisothiourea sulfate(SMT),on the metabolism of degenerative lumbar intervertebral disc so as to provide theoretical evidences for the clinical application of NOS inhibitor.METHODS:The experiment was conducted in the Key Laboratory for Children with Congenital Malformation,Ministry of Public Health from March 2003 to January 2004.Twenty degenerative lumbar intervertebral discs(nucleus and fibrous rings) were obtained from the patients undergoing disc surgery under sterile condition.The specimens were cultured in vitro and divided into two groups.The control group was not intervened with any drug.SMT group was intervened with 1 mmol/L SMT.After 72 hour culture,the release of nitric oxide(NO) and the activity of NOS in culture media were measured by detecting the concentrations of nitrate and nitrite salts.The expressions of inducible nitric oxide synthase(iNOS) mRNA and matrix metalloprotease 3(MMP3) mRNA were measured by in situ hybridization.The level of proteoglycan and releasing hydroxyproline in these specimens were measured with colorimetric analysis after 10 day culture.RESULTS:The NO release of nucleus and fibrous rings was significantly less in the SMT group than in the control group,and also the NOS activity lower in the former group than in the latter group(P< 0.01).After 10 day culture,the level of proteoglycan in discs of SMT groups was significantly higher than that in the control group(t=8.52,P< 0.01),and hydroxyproline release was markedly less in SMT group than that in the control group(t=6.58,P< 0.01).Meanwhile,the iNOS mRNA and MMP3 mRNA did not express.CONCLUSION:NOS inhibitor SMT can reduce NO over release and actively retard the process of lumbar intervertebral disc degeneration.更多还原