防止椎板切除术后硬脊膜外瘢痕粘连的实验研究

作者在４个平面间隔切除１１只山羊的椎板，分别用硅胶膜、自体游离脂肪片、带蒂肌肉瓣覆盖硬脊膜，一处平面作空白对照。术后４个月组织学检查，结果显示，硅胶膜后方有少许瘢痕组织增生，间质中有炎细胞灶状浸润，硅胶膜与硬膜囊无瘢痕形成，新形成的椎管后壁光滑，硬膜囊无受压；脂肪片被纤维组织取代，周围纤维组织增生轻微，形成菲薄之纤维膜，与硬脊膜容易分离；带蒂肌肉瓣周围形成较多瘢痕与硬脊膜粘连重，肌肉瓣已完全纤维化，空白组形成瘢痕最多，与硬脊膜粘连最重。术后硬膜囊矢状径以硅胶膜组最大，脂肪片组次之，带蒂肌肉瓣组再次之，空白组最小。作者认为，硅胶膜与脂肪片能明显防止椎板切除术后纤维瘢痕粘连对硬膜囊的压迫，在支架诱导作用方面，硅胶膜优于脂肪片，在生物相容性方面脂肪片优于硅胶膜。带蒂肌肉瓣优于对照组，但不及前两者。     

保存硬脊膜预防椎管内术后粘连的实验研究

28只大白兔随机分为实验和对照2组,均切除L5椎板,造成12mm×5mm的硬膜囊裸露区后,实验组用酒精保存的同种异体硬脊膜覆盖,对照组不用任何间置物覆盖、术后2、4、8、12周时进行肉眼及光镜观察,8周时还进行硬膜外粘连等级评定及病理切片的计算机图像分析。结果显示,对照组硬膜外腔消失,逐渐形成致密粘连,实验组硬膜外间隙存在,粘连明显少于对照组,揭示保存硬脊膜可以有效的预防椎管内术后粘连。     

椎板切除术后预防硬膜外瘢痕粘连的实验研究

为了寻找预防椎板切除后硬膜粘连的材料，选用家兔３０只，随机分为三组，每组１０只。每只作Ｌ３、Ｌ５椎板切除，形成两个大小１ｃｍ×０．５ｃｍ的缺损，一个缺损无任何覆盖，作空白对照；另一个缺损分别在硬膜外覆盖几丁糖、聚乳酸（ＰＬＡ）膜及明胶海绵，即为几丁糖组、ＰＬＡ膜组及明胶海绵组。术后２，４，６，８及１０周处死动物，通过肉眼、光镜及透射电镜，观察瘢痕生长及硬膜外粘连情况。结果表明，几丁糖组和ＰＬＡ膜组硬膜外均光滑、无增厚，硬膜外腔隙未见纤维组织增生或粘连；几丁糖具有明显抑制成纤维细胞生长和促进表皮细胞生长的作用，切口愈合快。而各组空白对照和明胶海绵组硬膜外纤维组织增生或粘连明显，硬膜外腔隙基本消失。认为，可生物降解吸收的几丁糖、ＰＬＡ膜能有效地预防椎板切除术后瘢痕粘连。     

预防椎板切除术后硬膜外粘连的实验研究

目的通过动物实验观察预防硬膜外粘连的有效材料和方法。方法５６只大白兔随机分为４组。切除Ｌ５椎板后造成１２ｍｍ×５ｍｍ硬脊膜裸露区,Ａ组不用任何间置物覆盖,Ｂ组充填质量分数为２％的透明质酸钠,Ｃ组用酒精保存的异体硬脊膜覆盖,Ｄ组用透明质酸钠充填后再用硬脊膜覆盖。术后２、４、８、１２周进行肉眼及光镜观察,８周还行硬膜外粘连等级评定及计算机图像分析。结果Ａ组硬膜外形成致密粘连,Ｂ、Ｃ组部分粘连,Ｄ组无明显粘连。结论保存硬脊膜与透明质酸钠联合应用为预防椎管内粘连最为有效的方法。     

自体真皮移植预防硬膜外纤维化及粘连的实验研究

目的 探讨自体真皮移植预防硬膜外纤维化及粘连的效果,为临床应用提供实验依据.方法 选取5头西藏小型猪,手术切除L2、L4全椎板造成缺损,去除硬膜后方硬膜外脂肪暴露硬脊膜,切取自体真皮移植于L2椎板缺损处覆盖硬脊膜(实验组),L4椎板缺损处硬脊膜外不用任何移植物覆盖(自身空白对照组).于术后2、4、6、8、10周全麻下股动脉放血法各处死1头动物,大体观察移植真皮存活情况及是否存在毛发生长、皮脂腺和汗腺分泌物.采用改良Robertson记分法评定硬膜外瘢痕量及粘连程度,SPSS 13.0统计学软件进行统计分析.组织学观察移植真皮内皮肤附属器变化情况.结果 移植真皮全部成活,与体表真皮比较明显增厚(P<0.05).实验组未见移植真皮毛发生长、皮脂腺囊肿和汗液囊肿形成;真皮与硬脊膜之间存在潜在的易分离平面,只有极少量瘢痕组织,粘连疏松,硬膜表面和移植真皮表皮面光滑.对照组大量的瘢痕形成,竖脊肌前方瘢痕组织严重且广泛长人硬膜外腔,与硬脊膜粘连紧密,硬脊膜从瘢痕组织上分离困难.改良Robertson记分法评分,实验组硬膜外瘢痕量及粘连程度明显低于对照组(P<0.05).组织学观察见毛囊萎缩、毛根坏死、皮脂腺及汗腺消失.结论 自体真皮是一种具有良好的抑制瘢痕形成和物理隔离屏障作用的生物材料.自体真皮移植能有效地预防硬膜外纤维化及粘连,具有临床应用价值.     

DL-PLA/CHI复合膜的防硬膜外粘连实验研究

目的　比较消旋聚乳酸 /甲壳素 (DL -PLA/CHI)膜 ,消旋聚乳酸 (DL -PLA)膜 ,几丁糖膜和聚四氟乙烯(ePTFE)膜防止硬膜外瘢痕粘连效果。方法　将 75只新西兰白兔随机分为 5组 ,施以全椎板切除术 ,分别予以放置消旋聚乳酸 /甲壳素 (DL -PLA/CHI)膜 ,消旋聚乳酸 (DL -PLA)膜 ,几丁糖膜和聚四氟乙烯 (ePTFE)膜防粘连处理 ,对照组不作特殊处理 ,通过大体观察、光镜观察瘢痕生长及硬膜外粘连情况。结果　DL -PLA组 ,DL -PLA/CHI组及ePTFE组硬膜外均光滑、无增厚 ,几丁糖组出现个别硬膜外腔隙纤维组织增生粘连。而空白对照组硬膜外纤维组织增生或粘连明显 ,硬膜外腔隙基本消失。几丁糖膜崩解吸收最快 ,DL -PLA/CHI膜较DL -PLA膜的崩解速度有所加快 ,但是机体的炎性反应明显减轻。瘢痕粘连形成的半定量评分结果经秩和检验 ,各实验组与对照组差异有非常显著性意义 ,而实验组之间无显著差异。结论　DL -PLA/CHI薄膜具有可靠的物理屏障作用 ,防止硬膜外瘢痕粘连效果良好。     

7.0T micro-MRI评价局部应用丝裂霉素C和消旋聚乳酸膜抑制大鼠硬膜外粘连及瘢痕形成

目的应用7.0Tmicro-MR比较单独应用丝裂霉素C（MMC）、消旋聚乳酸（DL-PLA）膜以及二者联合应用（MMC＋DL-PLA膜）时抑制大鼠椎板切除术后硬膜外粘连的效果。方法将16只SD大鼠随机分为4组,每组4只,椎板切除术后于硬膜外给予不同局部处理：单纯MMC组局部应用MMC 0.67mg/ml;单纯DL-PLA膜组给予生理盐水和0.05mm厚DL-PLA膜;MMC＋DL-PLA膜组给予MMC 0.67mg/ml和0.05mm厚DL-PLA膜;对照组单纯应用生理盐水。术后4周处死大鼠,分别行7.0Tmicro-MR扫描及瘢痕组织面积测定,并于镜下观察硬脊膜与后方瘢痕组织粘连情况。结果单纯MMC组和单纯DL-PLA膜组硬膜外瘢痕组织较疏松,瘢痕面积小,与硬脊膜部分粘连。MMC＋DL-PLA膜组硬膜外瘢痕组织较疏松,瘢痕面积更小,与硬脊膜未形成明显粘连。对照组标本硬膜外瘢痕组织致密,瘢痕面积大,与硬脊膜形成紧密粘连。结论局部单独应用浓度为0.67mg/ml的MMC或0.05mm厚的DL-PLA膜均能减少硬膜外瘢痕组织增生,二者联合应用时效果更显著。     

填充物预防椎板切除术后粘连的动物实验和临床观察

腰椎椎板切除术后常常由于硬膜外间隙形成的疤痕与硬脊膜粘连而出现一些并发症。为了防止术后疤痕粘连的形成,我们于1991年对筋膜片、游离脂肪和明胶海棉预防椎板切除术后的粘连做了动物实验观察和临床应用:     

聚乳酸凝胶预防硬膜外瘢痕粘连的实验研究

目的 探讨新型生物可吸收材料聚乳酸凝胶(polyactic acid glue，PLA-G)预防椎板切除术后硬膜外瘢痕粘连的作用。方法 切除24只成年日本大耳白兔的L2和L5椎板；在L5外露的硬膜及神经根表面喷涂液态PLA-G形成胶冻膜，为实验组；L2处只做椎板切除，为自身空白对照组。术后2、4、6、8、10及12周随机处死各4只兔，取标本行大体、组织学及超微结构的观察。结果 2周时实验组PLA-G未降解为机械屏障膜，硬膜与外侧瘢痕组织(scartissue，ST)间有明显间隙，光镜下显示间隙内无细胞；对照组为血肿覆盖较易分开，硬膜与ST间有血细胞团块，成纤维细胞(fibroblast，FB)增生活跃。4周时实验组PLA-G部分降解，机械屏障及间隙存在，光镜下ST中FB增多；对照组为较多质脆ST与硬膜广泛粘连，光镜下可见组织细胞浸润间隙，ST内FB明显多于实验组。6周时实验组PLA-G完全降解，少量ST与硬膜无粘连，光镜下FB已减少；对照组有大量质韧难以从硬膜分离的ST，FB继续增生活跃。8、10及12周时实验组ST与硬膜无粘连；对照组ST与硬膜粘连严重，光镜下见ST和硬膜粘连紧密伴毛细血管再造。超微结构观察：4周时实验组FB的粗面内质网较稀疏，分泌胶原纤维少；对照组FB的粗面内质网极丰富，胶原纤维多而成束。结论 PLA-G在实验兔腰椎板切除后的硬膜外能有效地减少瘢痕形成和粘连。     

应用人工硬脊膜预防瘢痕粘连早期临床观察

目的：介绍一种新的预防脊柱外科手术后瘢痕组织形成，硬膜粘连的一种方法，提高对椎板切除术后硬膜粘连的认识。方法：对17例腰椎间盘突出症椎板间开窗、间盘摘除的病人，术中应用美国戈尔公司生产的人造硬脊膜，术后3—6个月行核磁共振检查瘢痕组织的生成与硬膜粘连的情况。结果：17例应用人造硬脊膜的病人，3—6个月核磁共振示人造硬脊膜与脊髓之间无粘连，无瘢痕组织长入硬脊膜外空间，而同期手术的14例病人末应用此人工材料，其核磁共振影像均可见不同程度的瘢痕组织增生，脊髓与瘢痕组织粘连，神经根周围亦有瘢痕组织包裹、环绕。结论：人造硬脊膜有效降低了椎板切除术后瘢痕组织的产生程度，使病人减少了椎板切除术后瘢痕组织生成导致的疼痛，亦为二次手术创造了有利的条件。人造硬脊膜是一种比较理想的隔离物。     

Effect of polylactic acid glue in preventing epidural scar mdhesion after laminectomy in rabbits

Objective： To determine the efficacy of polylactic acid glue in preventing epidural scar adhesion after laminectomy in rabbits. Methods： Twenty-four Japanese white rabbits underwent laminectomy （including the attached ligaments） at Lz and Ls. After laminectomy at Ls, polylactic acid glue was sprayed on the dura and nerve roots and this segment was taken as the experimental group. After laminectomy at Lz, nothing was used and this segment was enrolled as the self control group. Four rabbits were killed every two weeks postoperatively till the end of the experiment at 12 weeks. Then the operated spine was observed grossly, histologically and ultrastructurally to check the degree of scar formation, the status of epidural scar adhesion, the absorption of the glue, and the intraceHular structure of fibroblasts. Results： The glue coagulated immediately after spraying and showed excellent hemostatic effect. The glue membrane was easy to be taken away from the dura mater of the samples for 2 weeks and there were no cells in the epidural space in the experimental group. But the dura mater was covered by hematoma in the control group,which formed mild adhesion, with fibroblasts proliferating actively. In the 4th week, some glue shivers remained in the epidural space with fibroblasts increasing a little, and the dura mater was smooth in the experimental group. However, in the control group, the formed scar was fragile and conglutinated with the dura mater diffusely and fibroblasts were much more than those in the experimental group. In the 6th-12th weeks, there was a potential interspace between the scar and the dura mater, and the polylactic acid glue was absorbed completely in the experimental group. Much tough scar was found in the control group, which was very difficult to dissect from the dura mater and the surrounding tissues. From the ultrastructural observation of the fibroblasts, the nucleus became much bigger and the rough endoplasmic reticulum was much more plentiful in the control group than that in the experimental group. Conclusions： Polylactic acid glue can effectively reduce epidural cicatrization and adhesion.     

Effect of polylactic acid glue in preventing epidural scar adhesion after laminectomy in rabbits

Objective: To determine the efficacy of polylactic acid glue in preventing epidural scar adhesion after laminectomy in rabbits. Methods: Twenty-four Japanese white rabbits underwent laminectomy (including the attached ligaments) at L2 and L5. After laminectomy at L5, polylactic acid glue was sprayed on the dura and nerve roots and this segment was taken as the experimental group. After laminectomy at L2, nothing was used and this segment was enrolled as the self control group. Four rabbits were killed every two weeks postoperatively till the end of the experiment at 12 weeks. Then the operated spine was observed grossly, histologically and ultrastructurally to check the degree of scar formation, the status of epidural scar adhesion, the absorption of the glue, and the intracellular structure of fibroblasts. Results: The glue coagulated immediately after spraying and showed excellent hemostatic effect. The glue membrane was easy to be taken away from the dura mater of the samples for 2 weeks and there were no cells in the epidural space in the experimental group. But the dura mater was covered by hematoma in the control group, which formed mild adhesion, with fibroblasts proliferating actively. In the 4th week, some glue shivers remained in the epidural space with fibroblasts increasing a little, and the dura mater was smooth in the experimental group. However, in the control group, the formed scar was fragile and conglutinated with the dura mater diffusely and fibroblasts were much more than those in the experimental group. In the 6th-12th weeks, there was a potential interspace between the scar and the dura mater, and the polylactic acid glue was absorbed completely in the experimental group. Much tough scar was found in the control group, which was very difficult to dissect from the dura mater and the surrounding tissues. From the ultrastructural observation of the fibroblasts, the nucleus became much bigger and the rough endoplasmic reticulum was much more plentiful in the control group than that in the experimental group. Conclusions: Polylactic acid glue can effectively reduce epidural cicatrization and adhesion.     

硬膜外注射倍他米松-利多卡因混合液对兔神经根炎症及硬膜外粘连的影响

目的 评价硬膜外注射倍他米松-利多卡因混合液对兔神经根炎症及硬膜外粘连的影响.方法 成年雄性新西兰大白兔24只,体重2.0～2.1 kg,采用随机数字表法,将兔随机分为2组(n=12):对照组和治疗组,在L2,3间隙进行硬膜外穿刺置管,置管后24 h注入消毒滑石粉0.5 mg/kg,制备神经根炎症及硬膜外粘连模型.给予滑石粉后3 d,治疗组经硬膜外导管注射倍他米松0.25mg/kg+利多卡因2.5 mg/kg,对照组给予等容量生理盐水.给予倍他米松+利多卡因后21 d,取脊髓和脊神经根,肉眼、光镜和电镜观察神经根和硬膜的病理学结果,并进行硬膜炎性细胞计数.结果 对照组神经根炎性反应和硬膜外粘连明显.治疗组未见明显和神经根炎性反应硬膜外粘连.治疗组硬膜炎性细胞计数(21±12)明显少于对照组(250±43)(P<0.01).结论 硬膜外注射倍他米松-利多卡因混合液可减轻兔神经根炎症及硬膜外粘连.

Abstract：

Objective To investigate the effects of epidural administration of a mixture of betamethasone and lidocaine on nerve root inflammation and epidural space adhesion in rabbits. Methods Twenty-four adult male New Zealand white rabbits weighing 2.0-2.1 kg, were randomly divided into 2 groups ( n = 12 each): control group and treatment group. A catheter was inserted into epidural space at L2,3 interspace. Twenty-four hour after epidural catheter placement, talcum powder 0.5 mg/kg was injected into epidural space to make the model of nerve root inflammation and epidural space adhesion. Three days later a mixture of lidocaine 2.5 mg/kg and betamethasone 0.25 mg/kg was injected via the epidural catheter in treatment group, while the equal volume of normal saline was given in control group. At 21 days after administration of lidocaine and betamethasone, the spinal cord was removed, and dura mater and nerve root were checked with naked eye, light microscope and electron microscope.The neutrophil count in the dura mater was determined. Results There was nerve root inflammation and epidural space adhesion in control group. The nerve root inflammation and epidural space adhesion was not observed in treatment group. The neutrophil count was reduced in treatment group (21 ± 12) compared with control group (250 ±43) ( P < 0.01) . Conclusion Epidural administration of a mixture of betamethasone and lidocaine can alleviate nerve root inflammation and epidural space adhesion.     

同种异体骨板覆盖预防硬膜外瘢痕粘连的实验研究

目的 探讨经冻干辐照处理后的同种异体骨板预防椎板切除术后硬膜外瘢痕粘连的作用。方法 12只成年雄性绵羊,随机分成A、B两组,每组6只。两组均作L3,4和L4,5椎板切除,A组的L4,5和B组的L3,4椎板缺损用“H”形同种冻干辐照骨板覆盖,为实验节段;A组的L3,4和B组的L4,5不覆盖骨板作为对照节段。于术后4、8、12、16、20和24周取材,行大体、X线平片和组织切片观察;并对4、24周取材行CT扫描。结果 术后4周,实验节段可见同种骨板形态、位置保持完好,椎管内无狭窄,硬膜囊无压迫,镜下椎板咬除缘有多量新生骨小梁生成,周边有大量软骨细胞及其分泌黏多糖和坏死后所留下的空腔,骨板内侧有增生纤维组织及少量炎性细胞浸润;对照节段可见大范围致密的纤维组织夹杂变性坏死肌肉嵌入椎板缺损处,硬膜广泛粘连,硬膜囊受压。术后24周,实验节段椎管重建基本完成,覆盖骨板吸收完全,并与再生椎板融合,椎管形态完好,硬膜外未见瘢痕组织;对照节段椎板再生未完成,瘢痕组织自椎管外嵌入椎管内,压迫硬膜囊及脊髓,硬膜外间隙几乎消失。统计学分析表明手术后期（16～24周）,实验节段与对照节段相比硬膜粘连程度明显减轻,椎管矢状径均较对照节段大,硬膜囊形状保持良好,无明显压迫。结论 同种异体冻干辐照骨板在实验羊椎板切除后的硬膜外能有效减少瘢痕形成和粘连。     

Chronic cervical and lumbar epidural catheterization through the atlanto-occipital membrane in rats

We report here an efficient means of epidural catheter placement through atlanto-occipital membrane in rats. METHODS: Male SD rats (n = 84) were divided into lumbar (n = 48) and cervical (n = 36) groups. Under sterile technique, PVC V-1 tubing was inserted and advanced caudally targeted to the C 4 or L 4 level. Analgesic efficacy and duration were measured by injecting increments of 2% lidocaine until a maximum paw withdrawal latency time from a radiant heat thermal stimulator. Rats (n = 6 each day) were sacrificed and an autopsy was performed to observe both the laterality of the catheter tip and the proliferation of fibrous tissue around the catheter. RESULTS: The volume of lidocaine and its duration was 52 +/- 17 microliters and 27 +/- 13 min (mean +/- SD) in lumbar, 30 +/- 10 microliters and 26 +/- 9 min in cervical group. In lumbar group, two catheters penetrated the dura. The remaining catheters were confirmed to be in the epidural space within L 4 +/- 1 or C 4 +/- 2 segment. Lumbar catheter tips were almost equally distributed between the center, left and right, while cervical catheter tips were distributed between left and center portion of the epidural space. The severity of tissue proliferation was time dependent. The proliferation of fibrotic tissue seemed more rapid in cervical than lumbar group. CONCLUSION: Although this approach for epidural catheter placement is efficient and produces excellent drug effects on day 3 after implantation, as reported by others, rapid development of fibrous tissue around the catheter quickly limits the usefulness of the epidural catheter.