摘要
目的探讨栀子苷(geniposide,GPO)对免疫球蛋白A肾病(immunoglobulin A nephropathy,IgAN)的作用及机制。方法将C57BL 6雌性小鼠随机分为对照(Control)组、IgA肾病(IgAN)组、栀子苷低、中、高剂量(GPO 25、50、100 mg)组、阳性药物对照组(Losartan 80 mg)组,每组20只。将NLRP3 KO小鼠随机分为NLRP3敲除小鼠IgA肾病(NLRP3 KO IgAN)组、NLRP3敲除小鼠IgA肾病给药(NLRP3 KO IgAN+GPO 100 mg)组,每组20只。通过施用牛血清白蛋白(bovine serum albumin,BSA)、脂多糖(lipopolysaccharide,LPS)和四氯化碳(carbon tetrachloride,CCl4)建立小鼠IgAN模型,采用灌胃给药,连续4周。通过全自动生化分析仪检测尿液中尿蛋白、血液中尿素氮(blood urea nitrogen,BUN)、血清肌酐(serum creatinine,Src);ELISA检测肾组织中IgA、白介素-1β(interleukin-1β,IL-1β)和IL-18的水平;HE染色观察病理变化;蛋白印迹检测肾组织中NLRP3表达;试剂盒检测肾组织中SOD和MDA含量。结果 GPO呈剂量依赖性降低IgAN小鼠24 h尿蛋白(P<0.05,P<0.01),降低IgAN小鼠血液中BUN和Src(P<0.05,P<0.01),减少IgAN小鼠肾组织中IgA沉积(P<0.05,P<0.01),缓解IgAN小鼠肾小球系膜扩张和炎性细胞的浸润,减轻IgAN小鼠肾组织炎症反应和氧化应激(P<0.05,P<0.01),减少IgAN小鼠肾组织中NLPR3蛋白表达(P<0.05,P<0.01);敲除NLPR3与给药GPO 100 mg对IgAN小鼠具有类似作用,而GPO对敲除NLPR3的NLPR3 KO小鼠并无作用。结论GPO通过调节NLRP3来减轻IgAN模型小鼠炎症反应和氧化应激。
To investigate the effect of geniposide(GPO) on immunoglobulin A nephropathy(IgAN) and the mechanism, female C57 BL6 mice were recruited and randomly divided into control group, IgAN group, low, medium and high doses of GPO(25, 50, 100 mg) groups, and positive drug control(Losartan 80 mg) group, with 20 mice in each group. NLRP3 KO mice were randomly divided into NLRP3 KO IgAN group and NLRP3 KO IgAN + GPO 100 mg group, with 20 mice in each group. IgAN model was established by administration of bovine serum albumin(BSA), lipopolysaccharide(LPS) and carbon tetrachloride(CCl4). The mice were administered by intragastric administration for 4 weeks. Then, urine protein, blood urea nitrogen(BUN) and serum creatinine(Src) were detected by automatic biochemical analyzer;the levels of IgA, interleukin(IL)-1β and IL-18 in renal tissues were detected by ELISA. Furthermore, the pathological changes in kidney were observed by HE staining, the expression of NLRP3 in renal tissues was detected by Western blotting, and the SOD and MDA contents in the kidney tissue were detected by a kit. Data showed that GPO dose-dependently reduced 24 h urine protein in IgAN mice(P<0.05, P<0.01),decreased BUN and Src levels in blood(P<0.05, P<0.01), decreased IgA deposition in renal tissues(P<0.05, P<0.01). Furthermore, GPO also dosedependently relieved mesangial expansion and inflammatory cell infiltration in IgAN mice, alleviated renal tissue inflammation and oxidative stress(P<0.05, P<0.01), and decreased the expression of NLPR3 protein in renal tissues(P<0.05, P<0.01). Knockout of NLPR3 and administration of GPO 100 mg had similar effects on IgAN mice, whereas GPO had no effect on NLPR3 KO mice. In conclusion, GPO reduces inflammatory response and oxidative stress in IgAN model mice by regulating NLRP3.
作者
庞欣
张建伟
庞欣欣
陈小永
解红霞
PANG Xin;ZHANG Jianwei;PANG Xinxin;CHEN Xiaoyong;XIE Hongxia(Department of Nephrology,Second Affiliated Hospital,Henan University of Traditional Chinese Medicine,Zhengzhou 450002 Henan,China)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2020年第10期870-876,共7页
Immunological Journal
基金
2018年河南省高等学校重点科研项目(19A360009)
2018年河南省中医院院级课题(2018YJKT01)。
关键词
栀子苷
免疫球蛋白A肾病
炎症反应
氧化应激
Geniposide
Immunoglobulin A nephropathy
Inflammatory response
Oxidative stress
