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| TNFAIP3 Alleviating Lumbar Disc Herniation in Rats by Regulating the Sirt1/FOXO3/Wnt/β-catenin Axis |
| WANG Jing, LIU Dafeng |
| The Third Hospital of Heilongjiang, Heilongjiang Bei'an 164092, China |
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Abstract Objective: To investigate the effects of TNFAIP3 (TNFα-induced protein 3) on lumbar disc herniation (LDH) in rats and explore its potential underlying mechanisms. Methods: A rat model of LDH was established through autologous nucleus pulposus transplantation. Eight healthy rats were used as the sham operation group, undergoing the same procedures as the modeling rats except for the placement of the nucleus pulposus. Five days after modeling, the model rats were randomly divided into four groups: model group, positive control group (ibuprofen, 20mg/kg), AAV empty virus group, and TNFAIP3 overexpression group (150 μL AAV-R-TNFAIP3, 1×1012vg/mL), with eight rats in each group. The positive control group received an intraperitoneal injection of ibuprofen at 20mg/kg. The TNFAIP3 overexpression group received an intraperitoneal injection of AAV-R-TNFAIP3 viral vector, while the AAV empty virus group received an equal volume of AAV empty viral vector, both administered once a week. The sham operation and model groups received daily intraperitoneal injections of an equal volume of saline throughout the study period. After four weeks of continuous treatment, the mechanical paw withdrawal threshold (MPWT) was assessed using the Von Frey filament test to evaluate the analgesic effect. Pathological changes in lumbar tissues were observed by hematoxylin and eosin (HE) staining. Serum levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression of TNFAIP3, Sirt1, FOXO3, Wnt3a, and β-catenin in lumbar tissues were detected by qRT-PCR and Western Blot, respectively. Results: Compared with the sham operation group, the model and AAV empty virus groups showed significantly decreased MPWT (P<0.05), increased inflammatory cell infiltration and pathological damage in lumbar tissues (P<0.05), elevated serum levels of TNF-α, IL-1β, and IL-6 (P<0.05), and downregulated mRNA and protein expression of TNFAIP3, Sirt1, and FOXO3 (P<0.05) with upregulated Wnt3a and β-catenin (P<0.05) in lumbar tissues. Compared with the model group, the positive control and TNFAIP3 overexpression groups exhibited significantly increased MPWT (P<0.05), reduced inflammatory cell infiltration and pathological damage in lumbar tissues (P<0.05), and decreased serum levels of TNF-α, IL-1β, and IL-6 (P<0.05). Notably, the TNFAIP3 overexpression group showed significantly upregulated mRNA and protein expression of TNFAIP3, Sirt1, and FOXO3 (P<0.05) and downregulated Wnt3a and β-catenin (P<0.05) in lumbar tissues. Conclusion: TNFAIP3 improves the symptoms and pathological changes of LDH in rats by modulating the Sirt1/FOXO3/Wnt/β-catenin axis.
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2025, Vol. 31 
