目的 探究毛蕊花糖苷（Verb）调控硫氧还蛋白相互作用蛋白（TXNIP）/NOD样受体蛋白3（NLRP3）通路对发育期惊厥性脑损伤大鼠神经炎症的影响。方法 将大鼠随机分为对照组、模型组、Verb低和高剂量（5、10 mg·kg^-1）组、TMAO（NLRP3激活剂，110 mg·kg^-1）组、Verb（10 mg·kg^-1） ＋TMAO（110 mg·kg^-1）组，每组12只，除对照组外，采用ip 5× 10⁶ U的青霉素的方式构建大鼠模型，Verb ip给药，TMAO ig给药，每天1次，连续28 d。新物体识别实验检测大鼠认知能力；记录大鼠惊厥强度评分、发作潜伏期与发作持续时间；苏木精-伊红（HE）染色检测海马组织病理损伤；尼氏染色检测神经元存活情况；酶联免疫吸附试验（ELISA）检测氧化应激指标和炎症反应指标水平；免疫荧光法检测离子钙结合适配分子1（Iba-1）和胶质纤维酸性蛋白（GFAP）阳性表达； Western blotting法检测TXNIP、NLRP3、凋亡相关斑点样蛋白（ASC）和半胱氨酸天冬氨酸蛋白酶1（Caspase-1）蛋白表达。结果 与对照组比较，模型组大鼠认知能力下降，大鼠惊厥强度评分和发作持续时间增加，海马组织病理损伤加重，尼氏小体数量减少，超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性降低，丙二醛（MDA）、白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）含量，Iba-1和GFAP阳性表达以及TXNIP、NLRP3、ASC、Caspase-1蛋白表达量明显升高（P＜0.05）；与模型组比较，Verb低和高剂量组大鼠认知能力提高，大鼠惊厥强度评分和发作持续时间减少，发作潜伏期延长，海马组织病理损伤减轻，尼氏小体数量增多，SOD和GSH-Px活性升高，MDA、IL-1β和IL-18含量，Iba-1、GFAP阳性表达以及TXNIP、NLRP3、ASC、Caspase-1蛋白表达量明显降低（P＜0.05）；与模型组比较，TMAO组大鼠认知能力下降，惊厥强度和发作持续时间增多，发作潜伏期缩短，脑组织神经炎症损伤程度更严重，尼氏小体数量减少，SOD和GSH-Px活性降低，MDA、IL-1β和IL-18含量，Iba-1和GFAP阳性表达以及TXNIP、NLRP3、ASC和Caspase-1蛋白表达量明显升高（P＜0.05）；与Verb高剂量组比较，Verb＋TMAO组大鼠认知能力下降，惊厥强度评分和发作持续时间增加，发作潜伏期缩短，海马组织病理损伤加重，尼氏小体数量减少，SOD和GSH-Px活性降低，MDA、IL-1β和IL-18含量，Iba-1和GFAP阳性表达以及TXNIP、NLRP3、ASC、Caspase-1蛋白表达量明显升高（P＜0.05）。结论 Verb可能通过抑制TXNIP/NLRP3通路，减轻惊厥大鼠炎症、氧化应激及脑组织损伤，改善认知能力。

Objective To discuss the effect of verbascoside (Verb) on neuroinflammation in rats with developmental convulsive brain injury by regulating the thioredoxin interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) pathway. Methods The rats were randomly divided into a control group, a model group, Verb low and high dose (5, 10 mg·kg^-1) groups, a TMAO (NLRP3 activator, 110 mg·kg^-1) group, and a Verb (10 mg·kg^-1) + TMAO (110 mg·kg^-1) group, with 12 rats in each group. Except for the control group, the rat model was established by ip injection of 5 million U of penicillin. Verb was administered ip, and TMAO was administered ig, once daily for 28 consecutive days. The cognitive ability of the rats was assessed using the novel object recognition test, the convulsive intensity score, seizure latency, and seizure duration of the rats were recorded, hematoxylin-eosin (HE) staining was used to detect histopathological damage in the hippocampus, Nissl staining was used to assess neuronal survival, enzyme-linked immunosorbent assay (ELISA) was used to measure levels of oxidative stress and inflammatory response indicators, immunofluorescence was used to detect the positive expression of ion calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP), and Western blotting was used to detect the protein expression of TXNIP, NLRP3, apoptosis-related speck-like protein (ASC), and cysteine aspartate protease 1 (Caspase-1). Results Compared with control group, the cognitive ability of rats in the model group decreased, the convulsion intensity score and seizure duration of rats increased, the pathological damage of hippocampal tissue aggravated, the number of Nissl bodies decreased, and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) decreased, the contents of malondialdehyde (MDA), interleukin-1β (IL^-1β), and interleukin-18 (IL^-18), the positive expressions of Iba-1 and GFAP, and the protein expression levels of TXNIP, NLRP3, ASC and Caspase-1 were prominently increased (P<0.05). Compared with model group, the cognitive ability of rats in the Verb low and high group was improved, the seizure intensity score and seizure duration of rats were reduced, the seizure latency was prolonged, the pathological damage of hippocampal tissue was alleviated, the number of Nissl bodies was increased, and the activities of SOD and GSH-Px were elevated, the contents of MDA, IL^-1β and IL^-18, the positive expressions of Iba-1 and GFAP, and the protein expression levels of TXNIP, NLRP3, ASC and Caspase-1 were prominently decreased (P<0.05). In the TMAO group, the cognitive ability of rats decreased, the intensity and duration of convulsions increased, the latency of convulsions shortened, the degree of neuroinflammatory injury in brain tissue was more severe, the number of Nissl bodies decreased, and the activities of SOD and GSH-Px decreased, the contents of MDA, IL^-1βand IL^-18, the positive expressions of Iba-1 and GFAP, and the protein expression levels of TXNIP, NLRP3, ASC and Caspase-1 were significantly increased (P<0.05). Compared with Verb high dose group, the cognitive ability of rats in the Verb high dose + TMAO group decreased, the seizure intensity score and seizure duration of rats increased, the seizure latency shortened, the pathological damage of hippocampal tissue aggravated, the number of Nissl bodies decreased, and the activities of SOD and GSH-Px decreased, the contents of MDA, IL^-1β and IL^-18, the positive expressions of Iba-1 and GFAP, and the protein expression levels of TXNIP, NLRP3, ASC and Caspase-1 were significantly increased (P<0.05). Conclusion Verb can alleviate inflammation, oxidative stress response, and brain tissue damage, and improve cognitive ability in convulsive rats by inhibiting TXNIP/NLRP3 pathway.

R965

江西省自然科学基金课题（20242BAB25474）；江西省中医药管理局科技计划项目（2025022718）