ABSTRACT
Purpose: To examine the differences in gene expression between ruptured and non-ruptured nucleus pulposus tissues of the intervertebral discs using gene chip technology. Methods: A total of 8 patients with nucleus pulposus from a lumbar disc herniation (LDH) undergoing discectomy in our hospital were selected, including 4 ruptured and 4 non-ruptured herniated nucleus pulposus cases. Total RNA was extracted from cells by using TRIzol reagent. Nucleus pulposus cDNA probes of the two groups were obtained by the single marker method and hybridized with a human gene expression profiling chip (Agilent). The fluorescence signal images were scanned by a laser, and the obtained genes were analyzed by bioinformatics. Results: There were 75 differentially expressed genes with more than 2-fold-changes, of which 56 were up-regulated and 19 were down-regulated. The differential expression of THSD7A, which was up-regulated 18 times, was the most significant, followed by CCL5, AQP3 and SDC4. Conclusion: THSD7A can be used as a characteristic differentially expressed gene in human ruptured nucleus pulposus. Moreover, CCL5, AQP3 and SDC4 may improve the chemotaxis of stem cell migration for self-healing of damaged disc tissue, increase water uptake by nucleus accumbens cells, and inhibit the inflammatory response, thus delaying the process of intervertebral disc degeneration.
ABSTRACT
Autophagy has been proved to occur in rats with intervertebral disc degeneration (IVDD). Yiqi Huoxue recipe (YQHXR), an effective therapy of traditional Chinese medicine, was widely used for ruptured lumbar disc herniation under clinical observation. More importantly, YQHXR positively regulated the expression of autophagy-related proteins. However, little is known about the significance of YQHXR in the pathologic process of IVDD. Therefore, this study explored the protective effect of YQHXR based on IVDD rat model through magnetic resonance imaging and histopathologic analysis. Then we evaluated the formation of autophagosomes in the degenerated intervertebral disc by transmission electron microscope. Real-time PCR was used to detect the changes of autophagy-related genes. Western blot and immunoprecipitation were used to assess the protein expression of the autophagy-related pathway. We found that YQHXR-induced autophagy attenuated the release of inflammatory factors. In addition, YQHXR promoted the formation of Beclin1-VPS34 complex to activate autophagy through not only activation of the upstream protein AMPK and upregulation of the deubiquitinase USP13, thus in turn alleviating the development of IVDD. We proposed the potential molecular mechanism of YQHXR on autophagy for the first time, so as to provide a theoretical and experimental basis for the clinical application of YQHXR in the treatment of IVDD-related diseases.
ABSTRACT
BACKGROUND: There have been several recent reports of lumbar disc herniation (LDH) resorption; however, large sample studies are lacking, and the mechanism(s) underlying this phenomenon is unclear. OBJECTIVES: To explore the feasibility and clinical outcomes of conservative treatment for giant LDH and to analyze the factors affecting the resorption of giant LDH. STUDY DESIGN: Observational study and original research. SETTING: This work was performed at a University Hospital of Traditional Chinese Medicine, Nanjing University of Traditional Chinese Medicine. METHODS: From January 2008 to December 2019, 409 patients with giant LDH who initially underwent nonsurgical treatment in our hospital were followed for 1-12 years to analyze the rate of surgical intervention, calculate the rate of resorption of protrusions, and the rate of excellent clinical outcomes. RESULTS: Eighty-nine of the 409 patients (21.76%) underwent surgery, while the remaining 320 patients (78.24%) constituted the non-surgical treatment group. The Japanese Orthopaedic Association (JOA) score in the 320 patients changed from 10.22 ± 3.84 points to 24.88 ± 5.69 points after treatment, and the rate of excellent outcomes was 84.06%. Among the 320 patients in the non-surgical treatment group, the protrusion percentage decreased from 70.08±30.95% to 31.67 ± 24.42%. One-hundred and eighty-nine patients (59.06%) had > 30% resorption of protrusions, and 81 patients (25.31%) had a significant resorption of protrusions of > 50%. Among 189 patients with resorption, the shortest resorption interval was 1 month, and the longest was 8 years, with 77 patients (40.74%) showing resorption within 6 months, 51 (26.98%) within 6-12 months, and 61 patients (32.28%) after 12 months. LIMITATION: The main limitations are that all patients were from the same site, and there was a lack of multicenter randomized controlled trials with which to compare data. CONCLUSIONS: Patients with giant LDH are less likely to develop progressive nerve injury and cauda equina syndrome if their clinical symptoms improve after treatment. As long as there is no progressive nerve injury or cauda equina syndrome, conservative treatment is preferred for giant disc herniation. Resorption is more likely with greater disc protrusions in the spinal canal. A ring enhancement bull's eye sign) around a protruding disc on enhanced magnetic resonance imaging is an important indicator of straightforward resorption.
