【目的】探讨黄芪甲苷Ⅳ对系统性红斑狼疮 （SLE） 小鼠的治疗作用及机制。 【方法】将40只雌性自发性MRL/lpr SLE模型 小鼠随机分为5组，模型组、泼尼松组、黄芪甲苷Ⅳ组、黄芪甲苷Ⅳ+CHPG[核因子KappaB （NF-κB） 通路激活剂]组和黄芪甲 苷Ⅳ+尼日利亚菌素[NOD样受体家族含pyrin结构域蛋白3 （NLRP3） 激活剂]组，每组8只。以8只雌性MRL/MpJ小鼠作为正常 组。给药期间，称量体质量。给药结束后，称量脾脏、胸腺、肾脏质量，计算脏器指数，检测尿液样本中的24 h尿蛋白水 平，血液样本中生化指标肌酐 （SCr） 、血尿素氮 （BUN） ，自身抗体[抗核抗体 （ANA） 、抗双链DNA （dsDNA） 抗体、抗snRNP/ Sm抗体]，炎症介质[白细胞介素 （IL） -1β、IL-18]水平，采用苏木素-伊红 （HE） 染色观察肾组织病理损伤，Masson染色观察 肾组织纤维化，采用蛋白免疫印迹 （Western Blot） 法检测肾脏和脾脏组织中NF-κB/NLRP3炎症小体通路相关蛋白表达。 【结果】与模型组比较，泼尼松组和黄芪甲苷Ⅳ组小鼠体质量增加，脾脏指数、胸腺指数和肾脏指数降低，血清ANA抗体、 抗dsDNA抗体、抗snRNP/Sm抗体水平降低，SCr、BUN、24 h尿蛋白水平降低，IL-1β、IL-18水平降低，肾脏和脾脏组织 中p-p65/p65、p-IκBα/IκBα、cleaved caspase-1/pro caspase-1比值及NLRP3蛋白相对表达量降低 （均P＜0.05） ，肾组织病理 损伤和纤维化减轻，且2个给药组间比较，差异无统计学意义 （P＞0.05） 。NF-κB激活剂和NLRP3炎症小体激活剂能够在一 定程度上消除黄芪甲苷Ⅳ对SLE小鼠上述指标的改善作用。 【结论】黄芪甲苷Ⅳ能够改善SLE小鼠的免疫功能，减轻肾损伤和 炎症反应，其作用机制可能与其抑制NF-κB/NLRP3炎症小体途径的活化有关。

Objective To investigate the therapeutic effect and mechanism of astragaloside Ⅳ on systemic lupus erythematosus （SLE） mice. Methods A total of 40 female spontaneous MRL/lpr SLE model mice were randomly divided into five groups：model group，Prednisone group，astragaloside Ⅳ group，astragaloside Ⅳ + CHPG [nuclear factor KappaB （NF- κB） pathway activator] group and astragaloside Ⅳ + Nigerian [NOD-like receptor family pyrin domain containing protein 3 （NLRP3） activator] group，with eight mice in each group. Eight female MRL/MpJ mice were used as normal group. During the administration， the body mass was weighted. After administration，the spleen，thymus and kidney were weighted，and the organ index was calculated. The 24-hour urinary protein level in urine samples，the biochemical indexes of creatinine （SCr） ，blood urea nitrogen （BUN） ，autoantibodies [antinuclear antibody （ANA），anti-double-stranded DNA （dsDNA） antibody，anti-snRNP/Sm antibody］ and inflammatory mediators [interleukin（IL）-1β， IL-18］ in blood samples were detected. The pathological damage of renal tissue was observed by hematoxylin-eosin （HE） staining，and the fibrosis of renal tissue was observed by Masson staining. The expressions of NF-κB/NLRP3 inflammasome pathway-related proteins in kidney and spleen tissues were detected by Western Blot. Results Compared with the model group，the body mass of mice in prednisone group and astragaloside Ⅳ group increased，the spleen index，thymus index and kidney index were decreased，the serum levels of ANA antibody，anti-dsDNA antibody and anti-snRNP/Sm antibody were decreased，the levels of SCr，BUN and 24-hour urine protein were decreased，the levels of IL-1β and IL-18 wrere decreased，the ratios of p-p65/p65，p-IκBα/IκBα，cleaved caspase-1/pro caspase-1 and the relative expression of NLRP3 protein in kidney and spleen tissues were decreased （all P＜0.05）， and the pathological damage and fibrosis of renal tissue in SLE mice were alleviated，there being no significant difference between the two administration groups （P＞0.05） . NF-κB activator and NLRP3 inflammasome activator eliminated the improvement of astragaloside Ⅳ on the above indexes in SLE mice to a certain extent. Conclusion Astragaloside Ⅳ can improve the immune function of SLE mice，reduce renal injury and inflammatory response， and its mechanism may be related to its inhibition of the activation of NF-κB/NLRP3 inflammasome pathway.

R285.5

云南省中医联合专项-青年项目 （编号：202301AZ070001-142）