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.
Highlights
Intervertebral disc degeneration (IVDD) is known as a common disease closely related to accelerated or advanced signs of aging, responsible for several spine-related disorders, such as disc herniation, chronic low back pain, and spinal canal stenosis (Adams and Roughley, 2006; Tang et al, 2018)
To explore whether Yiqi Huoxue recipe (YQHXR) exerted a protective effect on intervertebral disc degeneration (IVDD) in vivo, we established a tail needle-punctured IVDD model with administration of YQHXR
The levels of inflammatory factors (IL-1β, TNF-α, and IL-6) of IVDD group were much higher than those of Sham group, which were suppressed by YQHXR administration (p < 0.01, Figures 2B–D)
Summary
Intervertebral disc degeneration (IVDD) is known as a common disease closely related to accelerated or advanced signs of aging, responsible for several spine-related disorders, such as disc herniation, chronic low back pain, and spinal canal stenosis (Adams and Roughley, 2006; Tang et al, 2018). The clinical symptoms of IVDD are mainly based on the degenerative changes of the intervertebral disc, leading to long-term lumbago and leg pain, neurological deficits, and loss of labor ability, which seriously affect the life quality of patients (Xiong et al, 2020). Caused by accumulation of injury on the basis of degenerative diseases, IVDD will further repeatedly attack the degeneration of the intervertebral disc.
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