Pyrrolidine dithiocarbamate alleviated rat cervical intervertebral disc degeneration via reducing tumor necrosis factor α and matrixmetalloproteinase 9 expression and its underlying mechanism / 中国药理学通报

ABSTRACT

Aim To observe the effect of pyrimidine dithiocarbamate (PDTC) on the variance of disc morphology and the expressions of TNF-α, MMP-9 in the cervical disc in cervical dynamic equilibrium rat models, and to investigate the roles of PDTC in the process of intervertebral disc degeneration and the mechanism involved.Methods Fifty-four SD rats were divided into three groups randomly, then the dynamic equilibrium rat model was established by cutting the nuchal superficial and deep muscle of the rats.The dynamic equilibrium rats with PDTC solution intraperitoneal injection after operations were defined as PDTC group (group A), the models with saline intraperitoneal injection after operations as saline group (group B), the rats of fake operation with saline intraperitoneal injection as blank group (group C), and the animals were sacrificed in batches 10 weeks, 12 weeks, 16 weeks respectively after operation.The C5, C6 vertebrae and C5/6 discs were harvested, and the disc morphology was observed.TNF-α, MMP-9 mRNA expressions were detected by q-PCR and protein expression was observed by Western blot.Results Compared with the saline group, the morphology of disc in PDTC group was destructed slightly and fiber ring arranged orderly.TNF-α, MMP-9 gene and protein expressions had no obvious changes (P>0.05) in blank group (group C) at each time point.The expressions of IL-6, MMP-9 mRNA increased with time in group B, but the amount increased fast firstly, and slow lately, reaching peak in 12 weeks.The expression of TNF-α, MMP-9 protein became steady in group B from 10 weeks compared with other time points(P>0.05).TNF-α, MMP-9 genes and proteins expression decreased obviously in PDTC group (group A) compared with saline group (group B) (P<0.01) at each time point, but higher than blank group C(P<0.01) at each time point.Conclusions TNF-α and MMP-9 are important inflammatory factors involved in rat cervical disc degeneration, PDTC relieves the degeneration of rat cervical disc by reducing the expression of TNF-α and MMP-9 via disturbing the NF-κB signal pathway probably, and PDTC may become potential medicine for disc degeneration.