| Background:Disc degeneration is one of the most causes of low back pain, which is the result of multiple factors, including nutritional factor. As the largest avascularity tissue in the human body, anything induced destroys of capillary network around the intervertebral disc will be the risk factor of nutritional supply and the predisposing factor of disc degeneration. Diabetes mellitus is a metabolic disease inducing not only the metabolic disturbance, but also microangiopathy. For that reason, some authors suggested that diabetes mellitus might be an influencing factor of disc degeneration. The coexistence of diabetic and lumbar spine disease may cause even greater limitation among the diabetic population when compared with nondiabetic one, prompting more aggressive treatment. Although there was few literature. the interactions between diabetes mellitus and the degenerations of intervertebral disc and endplates was still uncertain. Furthermore, the changes of extracellular matrix and metabolic factors of intervertebral discs in diabetes mellitus are still unknown.Objective:1. To study the influence of diabetes mellitus on disc degeneration Via clinical observation. and to discuss the relationship between diabetes mellitus and the degenerations of intervertebral disc and endplates: 2. To study the disc degeneration in classical diabetic rat model via radiology and histology, and to discuss whether the classical diabetic rat model could be a new animal model to study the disc degeneration;3. To study the changes of extracellular matrix in the intervertebral discs of rats, including the contents of water, collagen, and proteoglycan, and to study the interaction with the metabolic factors, for example, MMP-3, BMP-2 and TIMP-1. Methods:1. Baseline characteristics of 127 patients with low back pain were compared with those of selective operations for other chief complaints in a total of 145 patients in the constituent ratio:the rate and distribution of disc and endplate degenerations in the coexistence diabetic and low back pain patients compared with those without diabetes mellitus; the operative outcomes including VAS and ODI were evaluated between patients with or without diabetes mellitus;2. The study group including 20 SD rat was induced by STZ and both high glucose and fat diet for diabetic animal model:the disc height index on X ray and the signal intensity on T2-weighted MRI were examined at different time points (baseline.4-.8-. and 12-week):the histological examination including HE and Safranin O stains were evaluated at the same time, in order to demonstrate the influences of diabetes mellitus on disc degeneration in the animal model;3. The extracellular matrix in the intervertebral disc was evaluated, including the contents of water and GAG measured by DMMB. the changes of types I and II collagen, and the aggrecan measured by western blot: the mRNA levels of MMP-3. BMP-2 and TIMP-1 was evaluated by qPCR. Results:1. The constituent ratio in low back pain patients was significant higher than that in the patients with selective operations for other chief complaints (X2= 16.17. P<0.01); the rates of severe complications in diabetic population was much more than those in nondiabetic one, especially the hypertension (P<0.01) and osteoporosis(P<0.05):for the classification of intervertebral disc degeneration, Grade III in nondiabetic population was much more than that in diabetic one (P<0.05), however, Grade V in diabetic one was significant more than that in nondiabetic one (P<0.05); Modic Type 2 in diabetic one was also significant much more than that in nondiabetic one (P<0.05); there was no significant different in the outcomes of operations between two gourps (P>0.05);2. The constancy of the diabetic rat model inducing by STZ and high glucose and fat diet was good; on X ray, there were stenosis of intervertebral space and instability in the diabetic rats after 4-week; the stenosis of the space was significant less in both 8-and 12-week on X ray (P<0.01); the signal intensity on T2-weighte MRI also had a trend of attenuate in the study group (P<0.05); there was good dependability between histological and radiological evaluation;3. The content of water in study group was less and less, the outcomes were (68.2±6.2)% and (60.1±9.7)% in 8- and 12-week, respectively. There were statistical differences compared with those at the same time points (P<0.05, P<0.01); the content of GAG in study group was also decreased, and there was statistical differences at 8-week compared with control group (P<0.05); the expressions of aggrecan and collagen type II were decreased, but that of collagen type I was increased; when measured by qPCR, the mRNA level of MMP-3 was increased at both 8- (P<0.05) and 12-week (P<0.01); the mRNA level of BMP-2 was increased at 4-week (P<0.05), but decreased after that time point; the mRNA level of TIMP-1 was only increased at 12-week (P<0.05). Conclusion:1. Diabetes mellitus is one of the influencing factors of disc degeneration:there are much more severe complications in diabetic population than that in nondiabetic one; the end-stage of disc degeneration and Modic changes type 2 was much more in diabetic one:there is no difference in the outcomes between two groups;2. The constancy of diabetic rat model inducing by STZ is good, which could be used as an animal model for the studying of diabetes mellitus and disc degeneration; the disc degeneration is progressed when the diabetes mellitus is coexistence; 3. The contents of water and aggrecan were decreased in the intervertebral disc with diabetes mellitus, and the ratio of type I/II was increased; the abnormality changes of metabolic factors including MMP-3, BMP-2 and TIMP-1 may induce the disorders of extracellular matrix and the influencing factor of disc degeneration. |
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