Abstract: To investigate the effects of antioxidant stress of R-(+)-lipoic acid on apoptosis of nerve cells and on YAP/TAZ signaling pathway in brain tumor rats, fifty male SD rats were randomly divided into the Control group, the Model group, the R-(+)-lipoic acid group (RLA group), the N-acetyl-L-cysteine (NAC) group and the R-(+)-lipoic acid +NAC group (RLA+NAC group). All groups of C6 glioma model were established except the Control group. The RLA group was intraperitoneally injected with R-(+)-lipoic acid, the NAC group was intraperitoneally injected with NAC, the RLA+NAC group was intraperitoneally injected with both R-(+)-lipoic acid and NAC simultaneously, the Control group and the Model group were injected with the equal volume of normal saline. Each group was continuously intervened for 15 days. Tumor volume and tumor inhibition rate of rats in each group were recorded after the intervention. TUNEL fluorescence staining was used to detect the apoptosis of nerve cells in each group; malondialdehyde (MDA) was detected by the thiobarbiturate method; superoxide dismutase (SOD) was detected by the hydroxylamine method; total antioxidant capacity (TAC) was detected by the ferric reducing antioxidant power (FRAP) assay; the reduced glutathione (GSH) was detected by the microassay kit; the morphology of brain tissue was observed by hematoxylin and eosin (HE) staining; Western blot was used to detect the protein expression levels of Yes-associated protein (YAP), transcriptional co-activator with PDZ-binding motif (TAZ), large tumor suppressor kinase 1 (LATS1), cysteine-rich angiogenic inducer 61 (CYR61), and connective tissue growth factor (CTGF) in brain tissue. The study showed that compared with the Model group, the tumor volumes in all intervention groups (RLA group, NAC group, and RLA+NAC group) were significantly reduced (P<0.05), with the smallest tumor volume observed in the RLA+NAC group. Accordingly, the tumor inhibition rate of the RLA+NAC group was significantly higher than those of the RLA group and the NAC group (P<0.05), while there was no statistically significant difference between the RLA group and the NAC group (P>0.05). Histological observation revealed obvious neuronal apoptosis and abnormal tissue morphology in the Model group. In all intervention groups, neuronal apoptosis was reduced and tissue morphology was improved, with the most pronounced improvement observed in the RLA+NAC group. The results showed that compared with the Control group, the Model group and all intervention groups showed significantly increased contents of MDA, as well as protein expression levels of YAP, TAZ, CYR61, and CTGF (P<0.05), while the activities of SOD and TAC, the content of GSH, and the protein expression level of phosphorylated LATS1 (p-LATS1) were significantly decreased (P<0.05). Compared with the Model group, the aforementioned indicators in all intervention groups were reversed (P<0.05), with the RLA+NAC group exhibiting the most significant reversal effect (P<0.05). The RLA group and NAC group showed no significant differences in any of the aforementioned indicators (P>0.05). Under the conditions of this study, the antioxidant stress effect of R-(+)-lipoic acid is beneficial for alleviating excessive nerve cell apoptosis in rats with C6 glioma and regulating the YAP/TAZ-related pathway proteins.
Keywords: C6 glioma; R-(+)-lipoic acid; oxidative stress; Yes-associated protein; transcriptional co-activator with PDZ-binding motif
（Acta Laser Biology Sinica, 2026, 35(4): 361-368）