基因组学在椎间盘退变遗传病因学研究中的应用进展

椎间盘退变（intervertebral disc degeneration,IDD）是引发一系列脊柱相关疾患的病理基础,颈椎病、腰椎间盘突出症等IDD相关疾病已成为全球性公共健康问题,严重影响患者的生活质量并给社会带来沉重的经济负担。研究表明,IDD是环境、遗传等多种因素综合影响的结果,其发病机制极其复杂,至今尚未完全阐明。早期观点认为IDD是由于随着年龄增大椎间盘衰老引发,然而近年来IDD疾患的发病呈现年轻化的趋势。因此,明确IDD的发病机制并寻求科学有效的治疗手段是当前的主要研究方向。研究显示,IDD具有很强的遗传倾向,因此在基因水平寻找其病因及发病机制,已成为国内外研究的热点。近年来高通量测序、高分辨质谱以及计算机综合支撑下的组学技术在生命科学领域发挥越来越重要的作用,其为阐明IDD发病的生物学机制提供了全新的思路和方法,弥补了传统遗传学研究的一些不足。在IDD研究中,主要通过以全基因组关联分析（genome-wide association study,GWAS）、全外显子测序（whole exon sequencing,WES）、DNA微阵列（DNA microarray）等技术来揭示IDD最初阶段的基因表达水平及调控机制,以期在DNA层面发现与IDD相关的突变基因和位点。在该方法及相关技术的助力下,IDD遗传学研究取得了飞速的发展,显著加快了IDD新靶点的发现。笔者就基因组学相关技术在IDD遗传病因学研究中的应用进展予以综述,以期为今后IDD相关疾患更加深入的研究提供参考。     

周期性牵张椎间盘纤维环细胞肌动蛋白骨架的重排

BACKGROUND: When the intervertebral disc is under stress, the hydraulic pressure generated inside the nucleus pulposus makes the annulus fibrosus extend outward and expand, and the annulus collagen fibers are stretched so that the extracellular matrix of annulus fibrosus cells is also under the pressure. In the intervertebral disc, aggrecan is the main component of proteoglycans, matrix metalloproteinase-2 is a major enzyme for extracellular matrix degradation, and tissue inhibitor of metalloproteinase is a multifunctional specific inhibition factor for matrix metalloproteinase activity. There is a mutual regulation between the latter two to keep the homeostasis between them. OBJECTIVE: To investigate the mechanism of cyclic tensile strain in the metabolism of intervertebral disc annulus matrix. METHODS: Rat anulus fibrosus cells were subjected to 2% or 10% cyclic tensile strain at 1.0 Hz for 2 and 12 hours using Flexcell4000 tension system. Then cells were collected and cultured in conditioned medium for gene and protein detection. Real-time quantitative PCR was used to detect mRNA expression of aggrecan, matrix metalloproteinases-2 and tissue inhibitor of metalloproteinase-2. Gelatin zymography was used to detect matrix metalloproteinases-2 activity. RESULTS AND CONCLUSION: The use of 2% cyclic tensile strain had no obvious effect on the stress fiber of actin cytoskeleton, whereas actin cytoskeleton was depolymerized in response to 10% cyclic tensile strain. The 2% cyclic tensile strain raised the expression of Aggrecan at 12 hours; whereas raised the matrix metalloproteinases-2 and tissue inhibitor of metalloproteinase-2 at 2 hours, both of which were in homeostasis; matrix metalloproteinases-2 activity had no significant changes. 10% cyclic tensile strain had no effect on the mRNA expression of Aggrecan. No matter stretching 2 or 12 hours, the matrix metalloproteinases-2 was up-regulated, and the tissue inhibitor of metalloproteinase-2 was down-regulated, both of which were not in balance. Moreover, the matrix metalloproteinases-2 activity was not significantly changed. These findings indicate that the mRNA expressions of Aggrecan, matrix metalloproteinases-2 and tissue inhibitor of metalloproteinase-2 alter in response to cyclic tensile strain in rat anulus fibrosus cells, and the tensile strain induces different mechano-responses in the actin cytoskeleton.      

经皮激光气化减压术治疗腰椎问盘突出症后椎问隙高度改变和中长期临床疗效

目的观察经皮激光气化减压术（pereutaneous laser disc decompression,PLDD）治疗腰椎间盘突出症后椎间隙高度的变化和中长期临床疗效。方法腰椎间盘突出症患者（L4-5）256例,行PLDD治疗,激光输出功率10w,脉冲时间1s,脉冲间隔时间1s。术后随访6、18和60个月,比较术前、术后手术节段椎间隙高度（intervertebral height,IH）变化、手术前后疼痛的VAS评分、Oswestry功能障碍指数（Oswestry Disability Index,ODI）和改良Menab疗效评分法,以评估临床疗效。结果术前、术后VAS疼痛评分及ODI评分较术前明显缓解（P〈0．05）;术前、术后手术节段椎间隙高度比较差异无显著性（P〉0．05）;术后18和60个月满意率（Menab评分优良者）分别为90．3％和86．2％。结论PLDD治疗腰椎间盘突出症远期效果好,同时可有效维持椎间隙高度。     

经皮穿刺激光椎间盘减压术治疗腰椎间盘突出症的疗效及其影响因素

目的分析经皮穿刺激光椎间盘减压术治疗腰椎间盘突出症的疗效及其影响因素。方法腰椎间盘突出症患者145例,应用经皮穿刺激光椎间盘减压术治疗,分别于术后7 d、3和12个月评定疗效。结果术后7 d、3和12个月的优良率分别为89.6%、92.4%和93.1%;17～40岁患者疗效明显优于40～60岁患者,而以61岁以上患者优良率最低;L3/L4、L4/L5和L5/S1椎间盘高度指数,术前分别为0.35±0.14、0.41±0.09和0.38±0.05,术后12个月分别为0.33±0.08、0.39±0.11和0.36±0.07,手术前后相比差异无显著意义。结论经皮激光气化减压术治疗椎间盘突出症近期和远期疗效良好,并发症少,不影响脊柱稳定性。术后时间及患者年龄是影响疗效的因素。     

脊柱侧凸椎体旋转半脱位三种测量方法的可重复性和可信度研究

【摘要】 目的：分析MB法（midbody,MB）、EP法（endplate,EP）和C法（centroid,C）在椎体旋转半脱位（rotatory subluxation,RS）测量中的可重复性和可信度,探讨三种测量方法的影响因素。方法：回顾性分析2012年3月～2020年6月于南京大学医学院附属鼓楼医院行手术治疗的59例脊柱侧凸畸形患者,其中先天性脊柱侧凸15例,特发性脊柱侧凸9例,退变性脊柱侧凸16例,神经肌源性脊柱侧凸19例;男17例,女42例,平均年龄34.0±18.8岁。3名脊柱外科医师均使用MB法、EP法及C法分别间隔两周测量RS值,用组内相关系数（intraclass correlation coefficient,ICC）对三种测量方法结果进行一致性分析。结果：59例患者平均主弯Cobb角为64.2°±23.9°。RS节段分别为T4/5节段1例（1.7%）、T5/6节段2例（3.4%）、T6/7节段3例（5.1%）、T7/8节段3例（5.1%）、T9/10节段1例（1.7%）、T10/11节段1例（1.7%）、T12/L1节段6例（10.2%）、L1/2节段5例（8.5%）、L2/3节段9例（15.3%）、L3/4节段16例（27.1%）、L4/5节段12例（20.3%）。MB法、EP法、C法测量的RS值分别为16.5±7.1mm、8.5±4.2mm、14.2±6.3mm。三种方法的观察者内一致性分别为MB法0.77-0.91、EP法0.78-0.81、C法0.82-0.94;观察者间一致性分别为MB法0.87、EP法0.90、C法0.86。结论：MB法、EP法和C法在RS的测量中均有较高的可重复性及可信度,其中C法的组内一致性最高、EP法的组间一致性最高。     

自制C形椎管内骨折复位器在胸腰段爆裂骨折后路手术中的应用

目的:评价自制C形椎管内骨折复位器在胸腰段爆裂骨折后路手术中对椎管内骨折块的复位效果。方法:将78例符合纳入标准(单节段胸腰段爆裂骨折,骨折块突入椎管,椎管狭窄,合并脊髓神经损伤等)的胸腰段爆裂骨折住院患者随机分入观察组和对照组,两组患者均行后路椎板减压椎管成形、钉棒系统内固定术。观察组在术中应用自制C形椎管内骨折复位器复位椎管内骨折块,对照组应用传统的直角形复位器复位椎管内骨折块。随访并评价两组患者术后局部矢状面Cobb角、伤椎椎体前后缘高度、伤椎椎管截面积以及脊髓神经功能的恢复情况。结果:观察组获得随访34例,对照组获得随访33例,随访时间均为6～12个月,观察组平均7.9个月;对照组平均7.8个月。末次随访时观察组与对照组的局部矢状面Cobb角分别平均恢复15.32°±5.81°和17.58°±7.33°;伤椎椎体前缘高度恢复率分别为(67.32±11.74)%和(66.67±10.78)%;伤椎椎体后缘高度恢复率分别为(54.68±20.13)%和(45.53±32.99)%;脊髓神经功能ASIA评分分别恢复34.53±19.81分和26.97±12.57分;Frankel分级恢复中位数分别为1.0(1.0,2.0)和1.0(1.0,1.0),两组之间的恢复率或恢复分值比较均无统计学差异(P>0.05)。观察组与对照组术后椎管截面积恢复率分别为(85.97±8.74)%和(76.30±6.64)%,组间比较有统计学差异(P<0.05)。结论:在胸腰段爆裂骨折后路手术中采用自制C形椎管内骨折复位器,对突入椎管内的骨折块进行复位,可较好地恢复椎管容积,优于传统的直角形复位器。     

经皮激光减压术治疗腰椎间盘突出症216例

目的观察经皮激光减压术治疗腰椎间盘突出症的疗效。方法对符合纳入标准的216例腰椎间盘突出症患者应用经皮激光间盘气化减压术治疗,分别于术后1周、3个月、1和3年进行随访,评定疗效。结果有效率、优良率术后3 d分别为56.9%、93.1%;术后3个月分别为80.8%、95.3%;术后1年分别为83.4%、94.5%;术后3年分别为82.8%、93.8%。术后1年内处于病情恢复阶段,1年后疗效稳定。结论经皮激光气化减压术治疗椎间盘突出症疗效确切、并发症少,远期效果好于近期效果。