基于Sirt介导的NF-κB/NLRP3信号通路探讨黄芪甲苷及莪术醇对慢性肾功能衰竭大鼠的作用机制研究  

Sirt Mediated NF-κB/NLRP3 Signaling Pathway Study on the Mechanism of Astragaloside Ⅳ and Curcumol on Rats with Chronic Renal Failure

作　　者：魏升 钟光辉 曹晓丹 陈孟廉 WEI Sheng;ZHONG Guanghui;CAO Xiaodan;CHEN Menglian

机构地区：[1]宁波市中医院,浙江宁波315010 [2]宁波市海曙区段塘街道社区卫生服务中心,浙江宁波315012

出　　处：《新中医》2022年第5期9-13,共5页New Chinese Medicine

基　　金：宁波市科技计划项目(2019A610363);宁波市科技计划项目(2017A610187)。

摘　　要：目的:基于Sirt介导的NF-κB/NLRP3信号通路探讨黄芪甲苷及莪术醇对慢性肾功能衰竭(慢肾衰)大鼠的作用机制。方法:制备大鼠慢肾衰模型,检测干预前后各组(正常组、模型组、黄芪甲苷组、莪术醇组、阳性对照组、益气化瘀组)大鼠血肌酐(SCr)、24 h尿蛋白水平。测定各实验组核转录因子(NF-κB)、NOD样受体蛋白3(NLRP3)、白细胞介素-1β(IL-1β)水平。PCR法、Western印迹法检测肾组织内沉默信息调控因子1(SIRT1)的mRNA表达水平。结果:与正常组大鼠比较,模型组大鼠造模后出现食欲下降、活动减少、精神萎靡、体质量减轻、尿量增加等症状,且上述症状逐渐加重;而给药组上述表现较轻。造模4周后,各组大鼠体质量都低于正常组(P<0.05,P<0.01);给药后,与正常组比较,各组体质量均降低(P<0.05,P<0.01),与模型组比较,各给药组体质量增加(P<0.05,P<0.01)。干预前(造模4周后),各模型组大鼠的SCr、24 h尿蛋白水平高于正常组(P<0.05,P<0.01)。干预后(12周),黄芪甲苷组、莪术醇组、阳性对照组、益气化瘀组的SCr、24 h尿蛋白水平高于正常组(P<0.05,P<0.01),但与模型组比较,显著降低(P<0.05)。与正常组比较,模型组的NF-κB、NLRP3、IL-1β水平均升高(P<0.01);与模型组比较,黄芪甲苷组、莪术醇组、阳性对照组、益气化瘀组的血清NF-κB、NLRP3水平均显著降低(P<0.05,P<0.01),阳性对照组和益气化瘀组的血清IL-1β水平显著降低(P<0.05,P<0.01)。与正常组比较,各造模组大鼠肾脏中SIRT1的mRNA相对表达量均显著降低(P<0.05,P<0.01)。各给药组的SIRT1 mRNA表达均有上升,与模型组比较,益气化瘀组SIRT1的m RNA相对表达量显著上升(P<0.05)。SIRT1的阳性表达主要定位于细胞核和细胞浆,呈棕黄色颗粒状。与正常组比较,造模各组的SIRT1阳性表达率均显著降低(P<0.01);与模型组比较,给药各组的SIRT1阳性表达率均有所上升,其中阳性对照组和益气化�Objective:Based on Sirt mediated NF-κB/NLRP3 signaling pathway to explore the mechanism of astragalosideⅣand curcumol on rats with chronic renal failure(CRF).Methods:The rat model of chronic renal failure was prepared,and the levels of serum creatinine(SCr)and 24 h urinary protein in each group(normal group,model group,astragalosideⅣgroup,Curcumol group,positive control group and Yiqi Huayu group)were detected before and after intervention.Nuclear transcription factor(NF-κB)was measured in each experimental group,nod like receptor protein 3(NLRP3),interleukin-1β(IL-1β).The mRNA expression level of silent information regulatory factor 1(SIRT1)in renal tissue was detected by PCR and Western blot.Results:Compared with the normal group,the rats in the model group had symptoms such as decreased appetite,decreased activity,depressed spirit,reduced body mass and increased urine volume,and the above symptoms gradually aggravated;while the above symptoms were mild in the administration groups.After 4 weeks of modeling,the body mass of rats in each group was lower than that in the normal group(P<0.05,P<0.01).After administration,the body mass of rats in each group decreased compared with the normal group(P<0.01).Compared with the model group,the body mass of each administration group increased(P<0.05,P<0.01).Before the intervention(after 4 weeks of modeling),the SCr and 24 h urinary protein level of each model group was higher than that of the normal group(P<0.01).After the intervention(12 weeks later),the SCr and 24 h urinary protein level of astragalosideⅣgroup,Curcumol group,positive control group and Yiqi Huayu group was higher than that of the normal group(P<0.01),but significantly lower than that of the model group(P<0.01).Compared with the normal group,NF-κB、NLRP3、IL-1βin the model group was significantly higher(P<0.01).The levels of serum NF-κB、NLRP3 in astragalosideⅣgroup,Curcumol group,positive control group and Yiqi Huayu group were significantly lower than those in model group(P<0.05,P<0.01

关 键 词：慢性肾功能衰竭 黄芪甲苷 莪术醇 炎症通路 

分 类 号：R692.5[医药卫生—泌尿科学]