Bradford D S, Oegema T R, Cooper K M, Wakano K, Chao E Y
Spine (Phila Pa 1976). 1984 Mar;9(2):135-47. doi: 10.1097/00007632-198403000-00004.
In the adult mongrel dog, in vivo injection of chymopapain into the intervertebral disc resulted, at two weeks, in disc space narrowing. However, [35S]sulfate labeling and proteoglycan characterization demonstrate that the nucleus retains the ability to synthesize proteoglycans, although they were degraded rapidly by residual proteolytic activity. Three months following chymopapain treatment, the intervertebral dog disc shows that an increase in disc height, return of nuclear material, and proteoglycan aggregate is present. At six months following chymopapain treatment, proteoglycans of similar characteristics to normal canine intervertebral disc are identified with a glucosamine/galactosamine ratio approaching normal values. Biomechanically, the short-term (30-120 minutes) in vitro effects of chymopapain appear to be the same as the carrier causing increased disc height, stiffness values, and creep rates. In the vivo study, after three weeks, chymopapain-injected discs had significant reductions in disc height and compressive stiffness, but the creep rate was increased substantially. However, at three months postinjection, these biomechanical properties began to reverse and approached those of the uninjected controls. The observations reported in this study suggest that chymopapain has a profound but reversible effect on normal canine intervertebral disc. The radiographic narrowing of the intervertebral disc following chymopapain injection correlates with loss of proteoglycan content, structure, and biomechanical properties. The restoration of normal disc height following chymopapain injection is explained by reconstitution of normal intervertebral disc. EDTA and cysteine used alone have no discernable in vivo enzymatic effect on intervertebral disc proteoglycan biochemistry. Chemonucleolysis with chymopapain would appear less likely to alter permanently proteoglycan biochemistry and the biomechanical properties of the disc than surgical excision in experimental animals.
在成年杂种犬中，向椎间盘内进行木瓜凝乳蛋白酶的体内注射，两周后导致椎间盘间隙变窄。然而，[35S]硫酸盐标记和蛋白聚糖特性表明，髓核保留了合成蛋白聚糖的能力，尽管它们会被残留的蛋白水解活性迅速降解。木瓜凝乳蛋白酶治疗三个月后，犬椎间盘显示椎间盘高度增加、髓核物质恢复以及蛋白聚糖聚集体出现。在木瓜凝乳蛋白酶治疗六个月后，鉴定出具有与正常犬椎间盘相似特征的蛋白聚糖，其氨基葡萄糖/半乳糖胺比值接近正常值。从生物力学角度来看，木瓜凝乳蛋白酶的短期（30 - 120分钟）体外效应似乎与载体相同，会导致椎间盘高度增加、刚度值和蠕变率增加。在体内研究中，三周后，注射木瓜凝乳蛋白酶的椎间盘的椎间盘高度和压缩刚度显著降低，但蠕变率大幅增加。然而，在注射后三个月，这些生物力学特性开始逆转并接近未注射对照组的特性。本研究报告的观察结果表明，木瓜凝乳蛋白酶对正常犬椎间盘有深远但可逆的影响。注射木瓜凝乳蛋白酶后椎间盘的影像学变窄与蛋白聚糖含量、结构和生物力学特性的丧失相关。注射木瓜凝乳蛋白酶后正常椎间盘高度的恢复是由于正常椎间盘的重构。单独使用乙二胺四乙酸（EDTA）和半胱氨酸对椎间盘蛋白聚糖生物化学在体内没有明显的酶促作用。在实验动物中，与手术切除相比，用木瓜凝乳蛋白酶进行化学髓核溶解似乎不太可能永久性改变椎间盘的蛋白聚糖生物化学和生物力学特性。
