[1]陈瑞丹,张彦,杨培丽,等.迷迭香酸通过抑制NADPH氧化酶/ROS/NLRP3炎症小体通路改善高血压肾病[J].陆军军医大学学报(原第三军医大学学报),2021,43(12):1153-1161.
 CHEN Ruidan,ZHANG Yan,YANG Peili,et al.Rosmarinic acid protects against hypertensive nephropathy by inhibiting NADPH oxidase/ROS/NLRP3 inflammasome pathway[J].J Amry Med Univ (J Third Mil Med Univ),2021,43(12):1153-1161.
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迷迭香酸通过抑制NADPH氧化酶/ROS/NLRP3炎症小体通路改善高血压肾病(/HTML )
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陆军军医大学学报(原第三军医大学学报)[ISSN:1000-5404/CN:51-1095/R]

卷:
43卷
期数:
2021年第12期
页码:
1153-1161
栏目:
基础医学
出版日期:
2021-06-30

文章信息/Info

Title:
Rosmarinic acid protects against hypertensive nephropathy by inhibiting NADPH oxidase/ROS/NLRP3 inflammasome pathway
作者:
陈瑞丹张彦杨培丽李方塘陈垦杨永健
西南交通大学临床医学院;,西部战区总医院心血管内科;陆军军医大学(第三军医大学)大坪医院心血管内科
 
Author(s):
CHEN Ruidan ZHANG Yan YANG Peili LI Fangtang CHEN Ken YANG Yongjian

School of Clinical Medicine, Southwest Jiaotong University,Chengdu, Sichuan Province, 610003; 2Department of Cardiovascular Medicine,General Hospital of Western Theater Command,Chengdu, Sichuan Province, 610003; 3Department of Cardiovascular Diseases, Daping Hospital,Army Medical University,Chongqing, 400010,China

关键词:
Keywords:
rrosmarinic acid hypertensive nephropathy NLRP3 inflammasome NADPH oxidase reactive oxygen species
 
分类号:
R544.1;R692;R965.1
文献标志码:
A
摘要:

目的探究迷迭香酸(rosmarinic acid,RA)对小鼠高血压肾病模型肾脏损伤的保护作用及其相关机制。方法30只6~8周龄雄性C57BL/6小鼠采用随机数字表法分为Control组,AngⅡ组(1.46 mg·kg-1·d-1),AngⅡ+RA组(AngⅡ 1.46 mg·kg-1·d-1+RA 50 mg·kg-1·d-1),每组10只,干预4周。检测血压、尿微量白蛋白、血肌酐及血尿素氮含量;免疫荧光检测肾组织巨噬细胞浸润情况;Masson染色检测肾组织纤维化程度;NADP+/NADPH检测试剂盒检测烟酰胺腺嘌呤二核苷酸磷酸(nicotinamide adenine dinucleotide phosphate,NADPH)氧化酶的活性;二氢乙啶超氧化物阴离子探针检测肾组织ROS水平;q-PCR及免疫印迹检测NADPH氧化酶亚基p22phox、p47phox及核苷酸结合寡聚化结构域样受体3(nucleotide-binding oligomerization domain,Leucine rich Repeat and Pyrin domain containing 3, NLRP3)、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein,ASC)、胱天蛋白酶1(caspase-1)、IL-1β、IL-18的表达水平。结果与Control组相比,AngⅡ组血压、尿蛋白、血肌酐、血尿素氮明显升高(P<0.05);肾脏炎症反应及纤维化程度显著增强(P<0.05)。迷迭香酸干预后,显著改善血压、尿蛋白、血肌酐及血尿素氮(P<0.05);减轻肾脏炎症反应和纤维化程度(P<0.05);NADPH氧化酶亚基p22phox及p47phox表达降低、活性下降(P<0.05);肾组织ROS水平降低(P<0.05);NLRP3炎症小体相关分子NLRP3、ASC、Caspase-1及其下游IL-1β、IL-18表达下降(P<0.05)。结论迷迭香酸通过调控NADPH氧化酶/ROS/NLRP3炎症小体通路改善高血压肾病。

Abstract:

ObjectiveTo investigate the protective effect of rosmarinic acid (RA) on hypertensive nephropathy in mice and its underlying mechanism.  MethodsThirty male C57BL/6 mice (6~8 weeks) were randomly divided into 3 groups: control group, AngⅡ group (Angiotensin II, 1.46 mg·kg-1·d-1) and AngⅡ+RA group (AngiotensinⅡ1.46 ·kg-1·d-1 + RA50 mg·kg-1·d-1), with 10 mice in each group, and were intervened for 4 weeks. Blood pressure, urinary microalbumin, serum creatinine and blood urea nitrogen were detected. Immunofluorescence assay and Masson staining were performed respectively to observe the macrophage infiltration and the severity of renal fibrosis. In addition, the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was determined using NADP+/NADPH test kit; and the level of reactive oxygen species (ROS) in renal tissue was tested by dihydroethidium (DHE) staining. Finally, the expression levels of NADPH oxidase subunits (p22phox, p47phox) and the following proteins were detected by RT-qPCR and western blotting: nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), Caspase-1, IL-1β and IL-18.  ResultsAs compared with the control group, the indicators of blood pressure, urinary microalbumin, serum creatinine and blood urea nitrogen, as well as inflammatory reaction and fibrosis severity of kidney were all significantly increased in AngⅡgroup (P<0.05). However, RA treatment significantly reversed all the above changes (P<0.05). Meanwhile, RA also decreased the expression of NADPH oxidase subunits (p22phox and p47phox) and the activity of NADPH oxidase(P<0.05). The level of ROS in renal tissue and the expression of NLRP3, ASC, Caspase-1, IL-1β and IL-18 were all reduced as well in AngⅡ+RA group.  ConclusionRA may play a protective role in hypertensive nephropathy by inhibiting the activation of NADPH oxidase/ROS/NLRP3 inflammasome pathway.

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更新日期/Last Update: 2021-06-25