Astragaloside IV attenuates nucleus pulposus cell injury in herniated discs via the miR-125a-5p/NLRP1 axis
Objective In human nucleus pulposus cells with IL-1β-induced degeneration,we investigated the effects of astragaloside IV(AS-IV)on signaling pathways mediated by miR-125a-5p and its target genes to reveal the effects of AS-IV on the proliferation,apoptosis,and inflammatory responses of human nucleus pulposus cells.Methods RT-qPCR was used to detect the expressions of miR-125a-5p and Nucleotide oligomerization domain(NOD)-like receptor protein 1(NLRP1)in the nucleus pulposus tissue of patients with disc herniation.IL-1β was used to induce nucleus pulposus cell degeneration,and the expressions of miR-125a-5p and NLRP1 were detected at the intervention concentrations of AS-IV at 20,50 or 80 μg·mL-1.The nucleus pulposus cells were treated with 80 μg·mL-1 AS-IV and IL-1β,and transfected with miR-125a-5p mimic and NLRP1 overexpression plasmid separately or jointly,and then the cell proliferation,apoptosis and secretion of inflammatory factors were detected respectively;Western blotting was used to detect the phosphorylation levels of signal pathway related proteins p56 and p38 in cells.Results MiR-125a-5p expression was down-regulated and NLRP1 expression was upregulated in nucleus pulposus tissues of lumbar disc herniation(LDH)patients.Intervention of IL-1β-treated nucleus pulposus cells with AS-IV promoted miR-125a-5p expression and reduced NLRP1 expression as well as phosphorylation levels of p56 and p38 proteins.AS-IV promoted nucleus pulposus cell proliferation,reduced apoptosis and the secretion of inflammatory factors in cells.Conclusion AS-IV reduces IL-1β-induced damage to nucleus pulposus by up-regulating the expression of miR-125a-5p,inhibiting the expressions of NLRP1 and activation of the NF-κB/MAPK signaling pathway.
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