六味二至四妙丸调控NF-κB信号通路介导治疗狼疮性肾炎作用机制的研究
Study on the mechanism of action of Liuwei Erzhi Simiao Pill on Attenuates lupus nephritis by regulating NF-κB signaling pathway
李松梅 1张玲忠 1尹蔚萍 1马殿飞 1吴招 1邹楠婷 1李小丝 1万春平 1夏杰1
作者信息
- 1. 云南中医药大学第一临床医学院,云南昆明 650021
- 折叠
摘要
目的:探讨六味二至四妙丸(LWEZSMW)调控NF-κB信号通路改善狼疮性肾炎的效应机制.方法:50只MRL/lpr自发性狼疮小鼠随机分为5组:模型组、阳性药物组(泼尼松龙2 mg·kg-1)、六味二至四妙丸低剂量组(9.45 g·kg-1)、中剂量组(18.90g·kg-1)和高剂量组(37.80g·kg-1).每组10只,连续给药干预35d后,考马斯亮蓝法检测各组小鼠蛋白尿水平.H&E染色检测小鼠肾脏病理损伤程度;免疫荧光检测各组小鼠肾脏免疫复合物沉积水平.流式细胞术检测各组小鼠脾脏和淋巴结CD11b+单核细胞比例.Western blot检测肾组织中p-IKB、p-NF-KB蛋白表达水平.结果:六味二至四妙丸药物干预后可显著减轻狼疮肾组织病理损伤,减少肾脏免疫复合物沉积,降低蛋白尿水平(P＜0.05);与模型组比较,六味二至四妙丸高剂量组淋巴细胞中CD11b+炎症细胞比例显著降低(P＜0.01),肾组织中p-IKB、p-NF-KB蛋白表达水平显著低于模型组(P＜0.05).结论:六味二至四妙丸对狼疮性肾炎具有明显保护效应,其机制可能与抑制NF-κB信号通路介导炎症反应有关,为六味二至四妙丸临床治疗系统性红斑狼疮(systemic lupus erythematosus,SLE)提供科学依据和生物学基础.
Abstract
OBJECTIVE To investigate the regulation of Liuwei Erzhi Simiao Pill(LWEZSMW)on NF-KB signaling path-way to improve lupus nephritis.METHODS Fifty MRL/lpr spontaneous lupus mice were randomly divided into 5 groups:model group,positive drug group(prednisolone 2 mg·kg-1)and LWEZSMW low dose group(9.45 g·kg-1),medium dose group(18.90 g·kg-1)and high dose group(37.80 g·kg-1)with 10 mice in each group.After 35 days of drug intervention,pro-teinuria was detected by Camas Brilliant Blue method,the degree of kidney pathological damage was detected by H&E staining,and the level of immune complex deposition was detected by immunofluorescence.Flow cytometry was used to detect the propor-tion of CD11b+ monocytes in the spleen and lymph nodes,The protein levels of p-IκB,NF-κB in the renal tissues were deter-mined by Western blot.RESULTS MRL/lpr mice treated with LWEZSMW showed significant reduction in renal damage.The proteinuria level,the deposition of immune complexes in the kidney and the proportion of lymphocytes and splenic lymphocytes CD11b+ inflammatory cells was significantly reduced in the high-dose group of LWEZSMW compared with the model group(P＜0.05 or P＜0.01);Meanwhile,the protein level of p-IκB、p-NF-κB were significantly reduced in the high-dose group(P＜0.05).CONCLUSION LWEZSMW can significantly alleviates lupus nephritis,and its underlying mechanism may be related to inhibit-ing NF-KB signaling pathway-induced inflammatory response,providing a scientific basis and biological foundation for LWEZSMW clinical treatment of systemic lupus erythematosus(SLE).
关键词
六味二至四妙丸/系统性红斑狼疮/狼疮性肾炎/NF-κB信号通路Key words
Liuwei Erzhi Simiao Pill/systemic lupus erythematosus/lupus nephritis/NF-κB signaling pathway引用本文复制引用
基金项目
云南省科技厅-云南中医药大学应用基础研究联合专项资金项目(2019FF002-045202001AZ070001-059)
云南省科技厅-云南中医药大学应用基础研究联合专项资金项目(202101AZ070001-116)
云南省教育厅治疗痹症中医中药工程研究中心项目(2023GYB08)
云南省科技人才和平台计划(202105AG070012)
云南省第五批中医药师带徒项目(云卫中医发展发[2020]2号)
出版年
2024
NETL
NSTL
维普
万方数据