摘 要：为研究右旋硫辛酸［R-(+)-硫辛酸］抗氧化应激对脑肿瘤大鼠神经细胞凋亡及YAP/TAZ信号通路的影响，本研究将50只SD雄性大鼠随机分为对照组（Control组）、模型组（Model组）、R-(+)-硫辛酸组（RLA组）、N-乙酰-L-半胱氨酸（NAC）组和R-(+)-硫辛酸+NAC组（RLA+NAC组）。除Control组外，其余组均建立C6脑胶质瘤大鼠模型。RLA组腹腔注射R-(+)-硫辛酸，NAC组腹腔注射NAC，RLA+NAC组同时腹腔注射R-(+)-硫辛酸和NAC，Control组、Model组注射等体积生理盐水。各组均持续干预15 d，记录干预后各组大鼠瘤体体积及抑瘤率。TUNEL荧光染色检测各组神经细胞凋亡情况；硫代巴比妥酸法检测丙二醛（MDA）；羟胺法检测超氧化物歧化酶（SOD）；铁离子还原抗氧化能力（FRAP）测定法检测总抗氧化能力（TAC）；微量检测试剂盒检测还原型谷胱甘肽（GSH）；苏木精-伊红（HE）染色观察脑组织形态；免疫印迹检测脑组织Yes相关蛋白（YAP）、含PDZ结合基序的转录共激活因子（TAZ）、大肿瘤抑制激酶1（LATS1）、富含半胱氨酸的血管生成诱导因子61（CYR61）、结缔组织生长因子（CTGF）的蛋白表达水平。研究表明，与Model组相比，各干预组（RLA组、NAC组、RLA+NAC组）的大鼠瘤体体积均显著减小（P<0.05），其中RLA+NAC组大鼠瘤体体积最小。RLA+NAC组的抑瘤率显著高于RLA组和NAC组（P<0.05），而RLA组与NAC组间的抑瘤率无统计学差异（P>0.05）。组织学观察显示：Model组神经细胞凋亡明显，组织形态异常；各干预组的神经细胞凋亡均有所减少，组织形态得到改善，其中RLA+NAC组的改善最为显著。与Control组相比，Model组及各干预组的MDA含量以及YAP、TAZ、CYR61、CTGF的蛋白表达水平均显著升高（P<0.05），而SOD和TAC活性、GSH含量及磷酸化LATS1（p-LATS1）蛋白表达水平则显著降低（P<0.05）。与Model组相比，各干预组的上述指标均得到逆转（P<0.05），其中RLA+NAC组逆转程度最大（P<0.05）。RLA组与NAC组在上述所有指标的比较中均无显著差异（P>0.05）。在本研究条件下，R-(+)-硫辛酸的抗氧化应激作用有利于改善C6脑胶质瘤大鼠神经细胞凋亡情况，并调节YAP/TAZ相关通路蛋白。
关键词：C6脑胶质瘤；右旋硫辛酸；氧化应激；Yes相关蛋白；含PDZ结合基序的转录共激活因子
中图分类号：R739.41      文献标志码：A    DOI：10.3969/j.issn.1007-7146.2026.04.009

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）