| Summary: | 博士 === 國立陽明大學 === 傳統醫藥研究所 === 105 === English Abstract
Intervertebral disc (IVD) degeneration is believed to contribute to low back pain. To understand the pathogenesis and regulatory mechanism of puncture-induced IVD degeneration, we established a rat-tail puncture model using Kirschner wire and a homemade stopper. The progress of disc degeneration was evaluated by histological examination and the quantitative measurement of type I and type II collagen expression at 0.5, 1, 2, 6, and 12 weeks after puncture and compared to control rats of the same age. The punctured disc demonstrated transient upregulation of Col2a1 and continuous upregulation of Col1a1 in nucleus pulposus. Histological examination and Safranin-O staining revealed progressive degeneration of the punctured disc. Matrix metalloproteinase 13 (MMP13) was increased at 1 week after puncture but did not change in the control group. Interleukin-1 beta (IL-1) mRNA expression level was elevated at the acute stage after puncture compared to the control group. A transient increase and then decrease in expression of hypoxia inducible factor 2 (HIF-2) in the nucleus pulposus (NP) was detected, followed by an increase at 12 weeks after puncture, while HIF-2 was upregulated with age in control nucleus pulposus. This model may potentially be valuable for the study of the molecular mechanisms and dissection of the pathways underlying disc degeneration.
Honokiol is one of the major compounds of Magnolia officinalis with ability to inhabit hypoxia inducible factor pathway and MMP13 expression. Honokiol can be a possible candidate in the treatment of intervertebral disc degeneration. To evaluate the distribution of honokiol into intervertebral disc, we developed in vitro and in vivo methods using high-performance liquid chromatography. The rat tail disc was used as the in vitro experimental model. For in vivo animal experiment, the blood samples and tail discs were collected from cardiac puncture and rat tail separately at 15, 30, 60, 120 and 240 min after honokiol administration (30 mg/kg, i.v.). A validated liquid chromatographic system was applied for honokiol analysis. The in vitro experimental results demonstrated that honokiol diffused into intervertebral disc and was concentration-dependent. Honokiol also distributed easily into the intervertebral disc after honokiol administration (30 mg/kg, i.v.). The concentration ratio of honokiol disc-to-plasma (Cdisc/Cplasma) is about 36% (1.79/4.91) at 15 min and about 49.6% (1.51/3.04) at 30 min after honokiol administration. These results demonstrated that application of traditional Chinese medicine in the treatment of intervertebral disc degeneration should be feasible. However, the therapeutic effect of honokiol in retardation of intervertebral disc degeneration should be further studied.
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