Suppr超能文献

小檗胺对系统性红斑狼疮小鼠的免疫调节作用

[The immunomodulatory effect of berbamine on mice with systemic lupus erythematosus].

作者信息

Wang Hui-Lian, Zhan Jun-Ping, Miao Xi-Yun, Meng Qing-Liang, Ma Jun-Fu

机构信息

Department of Rheumatology, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou 450053, China.

出版信息

Sheng Li Xue Bao. 2025 Jun 25;77(3):432-440. doi: 10.13294/j.aps.2025.0043.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by various complications, and the exact etiology remains unclear. Treatments for SLE encompass hormone therapy, plasma exchange and immunoadsorption, and targeted biological therapies. Berbamine (BBM), a cellular immunopotentiator with diverse biological functions, has not been reported to have immunomodulatory and therapeutic effects on SLE. The mice were divided into control group, model group, positive control group, low, medium and high BBM groups. In control group, C57BL/6J wild mice received intraperitoneal injection of saline. In model group, MRL/lpr lupus mice were treated with intraperitoneal injection of saline. In positive control group, MRL/lpr lupus mice received intragastric administration of hydroxychloroquine sulfate tablets [Plaquenil, 150 mg/(kg·d)]. In BBM groups, MRL/lpr lupus mice received intragastric administration of different concentration of BBM respectively [20 mg/(kg·d), 50 mg/(kg·d), 100 mg/(kg·d)]. After 8 weeks of treatment, blood was collected from the retro-orbital venous plexus, and ELISA was used to detect the levels of anti-double-stranded DNA (dsDNA) antibodies, antinuclear antibodies (ANA), and anti-small nuclear ribonucleoprotein/Sm (snRNP/Sm) antibodies. Spleen tissues were collected for analysis of Th1/Th2 ratio by flow cytometry. The RNA and protein of spleen were extracted, and the levels of T-box transcription factor T-bet and GATA3 (GATA binding protein 3) mRNA and protein were detected by qRT-PCR and Western blot. The proliferation of white blood cells in the blood was tested by blood routine test. The histopathological changes of kidneys of each group were detected by HE staining. Compared with the model group, the levels of ANA, anti-dsDNA, and anti-snRNP/Sm antibodies were significantly reduced in the BBM-treated groups. The Th1/Th2 ratio was significantly decreased in the model group, but reversed by BBM. Compared with the control group, T-bet expression was significantly downregulated, while GATA3 expression was significantly upregulated in the model group. After BBM intervention, T-bet expression significantly increased, while GATA3 expression decreased compared with the model group. The number of white blood cells significantly decreased in the model group, and increased in the BBM-treated groups. In the model group, the glomerular mesangial and endothelial cells showed significant hyperplasia, clear thrombus was observed in the dilated capillaries, and inflammatory cells infiltrated in the renal interstitium. In medium and high BBM groups, the infiltration of inflammatory cells and capillary thrombosis were significantly decreased. In conclusion, BBM exhibits certain immunomodulatory effects on SLE and promotes the proliferation of white blood cells.

摘要

系统性红斑狼疮(SLE)是一种伴有多种并发症的自身免疫性疾病,确切病因尚不清楚。SLE的治疗方法包括激素治疗、血浆置换和免疫吸附以及靶向生物疗法。小檗胺(BBM)是一种具有多种生物学功能的细胞免疫增强剂,尚未见其对SLE有免疫调节和治疗作用的报道。将小鼠分为对照组、模型组、阳性对照组、低、中、高剂量BBM组。对照组中,C57BL/6J野生小鼠腹腔注射生理盐水。模型组中,MRL/lpr狼疮小鼠腹腔注射生理盐水。阳性对照组中,MRL/lpr狼疮小鼠灌胃给予硫酸羟氯喹片[羟氯喹,150mg/(kg·d)]。在BBM组中,MRL/lpr狼疮小鼠分别灌胃给予不同浓度的BBM[20mg/(kg·d)、50mg/(kg·d)、100mg/(kg·d)]。治疗8周后,从眶后静脉丛取血,采用酶联免疫吸附测定(ELISA)法检测抗双链DNA(dsDNA)抗体、抗核抗体(ANA)和抗小核糖核蛋白/Sm(snRNP/Sm)抗体水平。取脾脏组织,采用流式细胞术分析Th1/Th2比值。提取脾脏的RNA和蛋白质,采用实时定量聚合酶链反应(qRT-PCR)和蛋白质免疫印迹法检测T盒转录因子T-bet和GATA结合蛋白3(GATA3)mRNA及蛋白质水平。通过血常规检测血液中白细胞的增殖情况。采用苏木精-伊红(HE)染色检测各组肾脏的组织病理学变化。与模型组相比,BBM治疗组的ANA、抗dsDNA和抗snRNP/Sm抗体水平显著降低。模型组Th1/Th2比值显著降低,但BBM可使其逆转。与对照组相比,模型组T-bet表达显著下调,而GATA3表达显著上调。BBM干预后,与模型组相比,T-bet表达显著增加,而GATA3表达降低。模型组白细胞数量显著减少,BBM治疗组白细胞数量增加。模型组肾小球系膜细胞和内皮细胞显著增生,扩张的毛细血管内可见清晰的血栓,肾间质有炎性细胞浸润。中、高剂量BBM组炎性细胞浸润及毛细血管血栓形成显著减少。综上所述,BBM对SLE具有一定的免疫调节作用,并能促进白细胞增殖。

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验