白花丹素减轻免疫球蛋白A肾病大鼠肾损伤的作用及机制  

Effects and mechanisms of plumbagin on reducing kidney injury in rats with immunoglobulin A nephropathy

作　　者：梁素忍[1] 郭志玲[1] 胡昭[2] 常洁[1] 刘俊英[1] 郭佳音[1] 陈豫闽[1] 李飞[1] 董少卿[1] 贾国强[1] LIANG Suren;GUO Zhiling;HU Zhao;CHANG Jie;LIU Junying;GUO Jiayin;CHEN Yumin;LI Fei;DONG Shaoqing;JIA Guoqiang(Department of Nephrology,the First Affiliated Hospital of Henan University of Science and Technology,Luoyang 471000,China;Department of Nephrology,Qilu Hospital of Shandong University,Jinan 250012,China)

机构地区：[1]河南科技大学第一附属医院肾内科,洛阳471000 [2]山东大学齐鲁医院肾内科,济南250012

出　　处：《免疫学杂志》2019年第12期1022-1029,共8页Immunological Journal

基　　金：山东省重点研发课题（2017GSF21116)

摘　　要：目的探究白花丹素(PLB)对免疫球蛋白A肾病(IgAN)大鼠肾脏损伤的缓解作用及其相关的机制。方法牛血清白蛋白+脂多糖+四氯化碳法建立IgAN大鼠模型,并通过灌胃给予PLB(50,100和200 mg·kg-1)处理。收集尿液检测蛋白尿,取心尖血检测血清肌酸酐(SCr)和尿素氮(BUN)。HE染色观察病理变化,TUNEL染色检测细胞凋亡;专用试剂盒检测肾组织部位氧化应激水平。另设N-乙酰半胱氨酸(NAC)200 mg·kg-1组,Western印迹和ELISA同步检测肾组织IL-18和IL-1β及其前体表达水平,Western印迹法检测肾组织NOD样受体热蛋白结构域3(NLRP3)、接头蛋白凋亡相关点状蛋白(ASC)和胱天蛋白酶1蛋白表达水平。结果与正常对照组比较,模型组肾组织尿蛋白、SCr、BUN浓度,细胞凋亡率和氧化应激水平升高,PLB(50、100和200 mg·kg-1)处理可显著降低肾组织尿蛋白、SCr、BUN含量,降低细胞凋亡及氧化应激水平。同时,NAC 200 mg·kg-1处理可显著降低氧化应激水平,降低IL-18和IL-1β及其前体蛋白表达,降低NLRP3/ASC/胱天蛋白酶1的蛋白表达;与200 mg·kg-1PLB处理有着一致的调控作用。结论 PLB可通过调控ROS抑制NLRP3激活,减轻IgAN大鼠肾脏损伤。This study aims to explore the relieving effect of plumbagin(PLB) on renal injury in rats with Immunoglobulin A nephropathy(IgAN) and its mechanism. An IgAN rat model was established by bovine serum albumin + lipopolysaccharide + carbon tetrachloride method and treated with PLB(50, 100 and 200 mg·kg-1) via i.g.Then the urine was collected to detect proteinuria, and the apical blood was gathered to detect serum creatine(SCr)and urea nitrogen(BUN). HE staining were used to observe the pathological changes, TUNEL staining were used to determine the cell apoptosis, while specific kits were used to detect oxidative stress levels in kidney tissue. A animal group of 200 mg·kg-1 N-acetylcysteine(NAC) was established, and the expressions of IL-18 and IL-1β as well as their precursors in renal tissues were determined by ELISA and Western blot. Western blot was used to detect the protein levels of NOD-like receptor pyrin domain containing three(NLRP3), apoptosis-associated speck-like protein(ASC) and Caspase-1. Data showed that the levels of proteinuria, SCr, BUN, cell apoptotic rate, oxidative stress in IgAN model group were increased significantly compared to normal control group, while 50, 100 and200 mg·kg-1 PLB treatment significantly decreased the concentrations of urinary protein, SCr and BUN in renal tissue, and decreased the level of apoptosis and oxidative stress. Meanwhile, treatment with 200 mg·kg-1 NAC significantly reduced oxidative stress,decreased IL-18 and IL-1β as well as their precursor protein expression, and decreased NLRP3/ASC/Caspase-1 protein expression, which were consistent with the effects of 200 mg·kg-1 PLB treatment. Taken together, PLB can inhibit NLRP3 activation by regulating ROS, thereby reducing renal damage in rats with IgA nephropathy.

关 键 词：白花丹素 IGAN 活性氧 NLRP3炎症小体 

分 类 号：R692.31[医药卫生—泌尿科学]