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

作　　者：李松梅 张玲忠 尹蔚萍 马殿飞 吴招 邹楠婷 李小丝 万春平 夏杰 LI Songmei;ZHANG Lingzhong;YIN Weiping;MA Dianfei;WU Zhao;ZOU Nanting;LI Xiaosi;WAN Chunping;XIA Jie(School of clinical medicine,Yunnan University of Chinese Medicine,Yunnan Kunming 650021,China)

机构地区：[1]云南中医药大学第一临床医学院,云南昆明650021

出　　处：《中国医院药学杂志》2024年第2期133-137,177,共6页Chinese Journal of Hospital Pharmacy

基　　金：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[编号:2019FF002(-045)、202001AZ070001-059和202101AZ070001-116];云南省教育厅治疗痹症中医中药工程研究中心项目(编号:2023GYB08);云南省科技人才和平台计划(编号: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)。

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(18.90 g·kg^(-1))和高剂量组(37.80 g·kg^(-1))。每组10只,连续给药干预35 d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-IκB、p-NF-κB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-IκB、p-NF-κB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。OBJECTIVE To investigate the regulation of Liuwei Erzhi Simiao Pil(l LWEZSMW)on NF-κB 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-κB 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 

分 类 号：R285[医药卫生—中药学]