毛蕊花糖苷调节HMGB1/RAGE/NF-κB信号通路对动脉粥样硬化大鼠内皮功能障碍的影响

doi:10.11958/20230325

天津医药 ›› 2023, Vol. 51 ›› Issue (12): 1339-1343.doi: 10.11958/20230325

毛蕊花糖苷调节HMGB1/RAGE/NF-κB信号通路对动脉粥样硬化大鼠内皮功能障碍的影响

刘艳文¹(), 刘水清¹, 林少伟¹, 刘协红²

1.江苏经贸职业技术学院（邮编211168）
2.湖南省人民医院（湖南师范大学附属第一医院）

收稿日期:2023-03-15 修回日期:2023-05-16 出版日期:2023-12-15 发布日期:2023-12-22
作者简介:刘艳文（1986），女，讲师，主要从事老年慢性病、老年营养与膳食方面研究。E-mail：lyw211168@163.com
基金资助:
教育部第二批国家级职业教育教师教学创新团队建设成果(教师函[2021]7号);江苏省高等学校基础科学（自然科学）面上项目(21KJB360014)

Effect of verbascoside on endothelial dysfunction in atherosclerotic rats by regulating HMGB1/RAGE signal pathway

LIU Yanwen¹(), LIU Shuiqing¹, LIN Shaowei¹, LIU Xiehong²

1. Jiangsu Vocational and Technical College of Economy and Trade, Nanjing 211168, China
2. Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University)

Received:2023-03-15 Revised:2023-05-16 Published:2023-12-15 Online:2023-12-22

刘艳文, 刘水清, 林少伟, 刘协红. 毛蕊花糖苷调节HMGB1/RAGE/NF-κB信号通路对动脉粥样硬化大鼠内皮功能障碍的影响[J]. 天津医药, 2023, 51(12): 1339-1343.

LIU Yanwen, LIU Shuiqing, LIN Shaowei, LIU Xiehong. Effect of verbascoside on endothelial dysfunction in atherosclerotic rats by regulating HMGB1/RAGE signal pathway[J]. Tianjin Medical Journal, 2023, 51(12): 1339-1343.

摘要/Abstract

摘要：

目的探讨毛蕊花糖苷（VB）调节高迁移率族蛋白B1（HMGB1）/晚期糖基化终产物受体（RAGE）/核因子κB（NF-κB）信号通路对动脉粥样硬化（AS）大鼠内皮功能障碍的影响机制。方法采用高脂饲料喂养联合维生素D3溶液腹腔注射的方法建立AS大鼠模型。将大鼠分为对照组（10只），模型组（12只），毛蕊花糖苷低、中、高剂量组（VB-L、M、H，2、5、10 mg/kg，每组10只）和阳性对照组（辛伐他汀，5 mg/kg，10只）。全自动生化分析仪检测血清中血脂水平；HE染色观察大鼠主动脉组织病理变化；酶联免疫吸附试验（ELISA）法检测血清中炎性因子及内皮细胞因子水平；微量法试剂盒检测大鼠氧化应激水平；Western blot检测主动脉HMGB1/RAGE信号通路蛋白表达。结果与对照组相比，模型组大鼠主动脉内膜增厚、血管出现斑块，并伴有脂质沉积和炎性细胞浸润，血清中总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）、C反应蛋白（CRP）、基质金属蛋白酶9（MMP-9）、内皮素1（ET-1）、内脂素、细胞间黏附分子1（ICAM-1）、丙二醛（MDA）及主动脉中HMGB1、RAGE、NF-κB磷酸化水平升高，高密度脂蛋白胆固醇（HDL-C）、一氧化氮（NO）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）水平降低（P<0.05）；与模型组相比，VB各组及辛伐他汀组大鼠病理学变化明显改善，血清中TC、TG、LDL-C、TNF-α、IL-1β、CRP、MMP-9、ET-1、内脂素、ICAM-1、MDA及主动脉中HMGB1、RAGE、NF-κB磷酸化水平降低，血清HDL-C、NO、SOD、GSH-Px水平升高（P<0.05）。结论 VB可下调HMGB1/RAGE/NF-κB信号通路蛋白表达，抑制AS大鼠炎症和氧化应激，改善脂质代谢和血管内皮功能。

关键词: 麦角甾苷, 动脉粥样硬化, HMGB1蛋白质, 高级糖化终产物受体, 内皮功能障碍, 毛蕊花糖苷

Abstract:

Objective To investigate the effect of verbascoside (VB) on endothelial dysfunction in atherosclerotic (AS) rats by regulating high-mobility group protein B1 (HMGB1)/receptor for advanced glycation endproducts (RAGE)/nuclear factor κB (NF-κB) signal pathway. Methods The rat model of AS was established by high fat feeding combined with vitamin D3 solution intraperitoneal injection. Rats were divided into the control group (n=10), the model group (n=12), the low (VB-L), medium (VB-M) and high dose (VB-H) VB groups (2, 5 and 10 mg/kg, n=10), and the positive control group (simvastatin, 5 mg/kg, n=10). The serum level of blood lipids was detected by automatic biochemical analyzer. Pathological changes of aorta were observed by HE staining. Serum levels of inflammatory factors and vascular endothelial cytokines were detected by enzyme-linked immunosorbent assay (ELISA). The level of oxidative stress in rats was detected by micro-method kit. The expression of HMGB1/RAGE signal pathway protein in aorta was detected by Western blot assay. Results Compared with the control group, the intima of aorta in the model group was thickened, plaque appeared in blood vessels, accompanied by lipid deposition and inflammatory cell infiltration. Serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), C-reactive protein (CRP), matrix metalloproteinase-9 (MMP-9), endothelin-1 (ET-1), visfatin, intercellular adhesion molecule-1 (ICAM-1) and malondialdehyde (MDA), and HMGB1, RAGE and phosphorylation levels of NF-κB in aorta were obviously increased. Serum levels of high-density lipoprotein cholesterol (HDL-C), nitric oxide (NO), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were obviously decreased (P<0.05). Compared with the model group, pathological changes of rats were obviously improved in the VB-L, VB-M and VB-H groups and the simvastatin group. Serum levels of TC, TG, LDL-C, TNF-α, IL-1β, CRP, MMP-9, ET-1, visfatin, ICAM-1, MDA, and HMGB1, RAGE, phosphorylation levels of NF-κB in aorta were obviously decreased, and serum levels of HDL-C, NO, SOD and GSH-Px were obviously increased (P<0.05). Conclusion VB can down-regulate the expression of HMGB1/RAGE/NF-κB signal pathway protein, inhibit inflammation and oxidative stress in AS rats, and improve lipid metabolism and vascular endothelial function.

Key words: acteoside, atherosclerosis, HMGB1 protein, receptor for advanced glycation end products, endothelial dysfunction, verbascoside

中图分类号:

R285.5

图/表 7

参考文献 21

[1]	VALLEJO J, COCHAIN C, ZERNECKE A, et al. Heterogeneity of immune cells in human atherosclerosis revealed by scRNA-Seq[J]. Cardiovasc Res, 2021, 117(13):2537-2543. doi:10.1093/cvr/cvab260.
[2]	XU S, ILYAS I, LITTLE P J, et al. Endothelial dysfunction in atherosclerotic cardiovascular diseases and beyond:from mechanism to pharmacotherapies[J]. Pharmacol Rev, 2021, 73(3):924-967. doi:10.1124/pharmrev.120.000096.
[3]	SOEHNLEIN O, LIBBY P. Targeting inflammation in atherosclerosis - from experimental insights to the clinic[J]. Nat Rev Drug Discov, 2021, 20(8):589-610. doi:10.1038/s41573-021-00198-1.
[4]	MA S, LU G, ZHANG Q, et al. Extracellular-superoxide dismutase DNA methylation promotes oxidative stress in homocysteine-induced atherosclerosis[J]. Acta Biochim Biophys Sin (Shanghai), 2022, 54(9):1222-1233. doi:10.3724/abbs.2022093.
[5]	FAN J, WATANABE T. Atherosclerosis:Known and unknown[J]. Pathol Int, 2022, 72(3):151-160. doi:10.1111/pin.13202.
[6]	ZHANG G, YU F, DONG R, et al. Verbascoside alleviates renal fibrosis in unilateral ureteral obstruction rats by inhibiting macrophage infiltration[J]. Iran J Basic Med Sci, 2021, 24(6):752-759. doi:10.22038/ijbms.2021.52759.11903.
[7]	FAN Y, ZHANG K. Verbascoside inhibits the progression of atherosclerosis in high fat diet induced atherosclerosis rat model[J]. J Physiol Pharmacol, 2021, 72(3):329-337. doi:10.26402/jpp.2021.3.03.
[8]	WANG J, LI R, PENG Z, et al. HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2,TLR4,and RAGE/NF-κB signaling pathways[J]. Int J Mol Med, 2020, 45(1):61-80. doi:10.3892/ijmm.2020.4530.
[9]	ZHANG X, FERNÁNDEZ-HERNANDO C. Endothelial HMGB1(high-mobility group box 1)regulation of LDL(low-density lipoprotein)transcytosis:a novel mechanism of intracellular HMGB1 in atherosclerosis[J]. Arterioscler Thromb Vasc Biol, 2021, 41(1):217-219. doi:10.1161/ATVBAHA.120.315517.
[10]	焦艳, 谢世静, 李喆. 沙棘黄酮对大鼠动脉粥样硬化斑块的影响及作用机制[J]. 中国老年学杂志, 2022, 42(6):1472-1475.
	JIAO Y, XIE S J, LI Z. Effect of sea-buckthorn flavone on atherosclerotic plaque in rats and its mechanism of action[J]. Chinese Journal of Gerontology, 2022, 42(6):1472-1475. doi:10.3969/j.issn.1005-9202.2022.06.055.
[11]	白荣钰, 易欢, 陈丰连, 等. 毛冬青三萜皂苷对动脉粥样硬化大鼠肠道菌群的影响[J]. 中草药, 2021, 52(20):6245-6253.
	BAI R Y, YI H, CHEN F L, et al. Effect of triterpenoid saponins from llex pubescens on intestinal flora in atherosclerotic rats[J]. Chinese Traditional and Herbal Drugs, 2021, 52(20):6245-6253. doi:10.7501/j.issn.0253-2670.2021.20.014.
[12]	MAN J J, BECKMAN J A, JAFFE I Z. Sex as a biological variable in atherosclerosis[J]. Circ Res, 2020, 126(9):1297-1319. doi:10.1161/CIRCRESAHA.120.315930.
[13]	WU M, GAO Y, CHEN B. Mechanism of acteoside-activated let-7g-5P attenuating Aβ-induced increased permeability and apoptosis of brain microvascular endothelial cells based on experimental and network pharmacology[J]. Neuroreport, 2022, 33(16):714-722. doi:10.1097/WNR.0000000000001837.
[14]	ZHANG S, HONG F, MA C, et al. Hepatic lipid metabolism disorder and atherosclerosis[J]. Endocr Metab Immune Disord Drug Targets, 2022, 22(6):590-600. doi:10.2174/1871530322666211220110810.
[15]	SHRAMKO V S, STRYUKOVA E V, KASHTANOVA E V, et al. Adipokines and adipocytokines in men with coronary atherosclerosis and overweight[J]. Kardiologiia, 2022, 62(11):49-55. doi:10.18087/cardio.2022.11.n2237.
[16]	JEON S, KIM T K, JEONG S J, et al. Anti-inflammatory actions of soluble ninjurin-1 ameliorate atherosclerosis[J]. Circulation, 2020, 142(18):1736-1751. doi:10.1161/CIRCULATIONAHA.120.046907.
[17]	LIU P, WANG S, WANG G, et al. Macrophage-derived exosomal miR-4532 promotes endothelial cells injury by targeting SP1 and NF-κB P65 signalling activation[J]. J Cell Mol Med, 2022, 26(20):5165-5180. doi:10.1111/jcmm.17541.
[18]	DORAN A C. Inflammation resolution:implications for atherosclerosis[J]. Circ Res, 2022, 130(1):130-148. doi:10.1161/CIRCRESAHA.121.319822.
[19]	KAKE S, KAWAGUCHI H, NAGASATO T, et al. Association between HMGB1 and thrombogenesis in a hyperlipaemia-induced microminipig model of atherosclerosis[J]. In Vivo, 2020, 34(4):1871-1874. doi:10.21873/invivo.11982.
[20]	JEONG J, LEE J, LIM J, et al. Soluble RAGE attenuates AngII-induced endothelial hyperpermeability by disrupting HMGB1-mediated crosstalk between AT1R and RAGE[J]. Exp Mol Med, 2019, 51(9):1-15. doi:10.1038/s12276-019-0312-5.
[21]	OLEJARZ W, GŁUSZKO A, CYRAN A, et al. TLRs and RAGE are elevated in carotid plaques from patients with moderate-to-severe obstructive sleep apnea syndrome[J]. Sleep Breath, 2020, 24(4):1573-1580. doi:10.1007/s11325-020-02029-w.

组别	n	TC	TG	HDL-C	LDL-C
对照组	10	1.42±0.18	0.62±0.12	2.25±0.34	1.75±0.40
模型组	12	2.08±0.25^a	1.41±0.30^a	0.96±0.36^a	6.10±0.72^a
VB-L组	10	1.80±0.21^b	1.12±0.20^b	1.42±0.28^b	5.39±0.60^b
VB-M组	10	1.65±0.24^b	0.79±0.25^bc	1.69±0.45^b	4.66±0.45^bc
VB-H组	10	1.49±0.16^bc	0.74±0.22^bc	1.88±0.32^bc	3.85±0.51^bcd
辛伐他汀组	10	1.52±0.18^bc	0.70±0.20^bc	1.92±0.30^bc	3.48±0.45^bcd
F		15.589^＊＊	20.348^＊＊	18.493^＊＊	86.051^＊＊

组别	n	TC	TG	HDL-C	LDL-C
对照组	10	1.42±0.18	0.62±0.12	2.25±0.34	1.75±0.40
模型组	12	2.08±0.25^a	1.41±0.30^a	0.96±0.36^a	6.10±0.72^a
VB-L组	10	1.80±0.21^b	1.12±0.20^b	1.42±0.28^b	5.39±0.60^b
VB-M组	10	1.65±0.24^b	0.79±0.25^bc	1.69±0.45^b	4.66±0.45^bc
VB-H组	10	1.49±0.16^bc	0.74±0.22^bc	1.88±0.32^bc	3.85±0.51^bcd
辛伐他汀组	10	1.52±0.18^bc	0.70±0.20^bc	1.92±0.30^bc	3.48±0.45^bcd
F		15.589^＊＊	20.348^＊＊	18.493^＊＊	86.051^＊＊

组别	n	TNF-α/（ng/L）	IL-1β/（ng/L）	CRP/（mg/L）	MMP-9/（μg/L）
对照组	10	189.15±36.74	20.32±4.01	1.23±0.15	70.22±5.15
模型组	12	323.06±34.15^a	30.98±3.57^a	4.68±0.20^a	105.32±8.23^a
VB-L组	10	276.24±38.20^b	26.01±3.70^b	2.73±0.18^b	79.24±7.01^b
VB-M组	10	258.20±39.21^b	24.61±3.78^b	2.70±0.15^b	82.24±8.01^bc
VB-H组	10	223.78±36.22^bc	21.75±3.12^b	2.45±0.16^bcd	78.42±7.52^bc
辛伐他汀组	10	245.21±35.25^b	22.53±3.01^b	2.30±0.14^bcd	85.20±9.31^b
F		17.078^＊＊	12.941^＊＊	513.455^＊＊	27.992^＊＊

组别	n	TNF-α/（ng/L）	IL-1β/（ng/L）	CRP/（mg/L）	MMP-9/（μg/L）
对照组	10	189.15±36.74	20.32±4.01	1.23±0.15	70.22±5.15
模型组	12	323.06±34.15^a	30.98±3.57^a	4.68±0.20^a	105.32±8.23^a
VB-L组	10	276.24±38.20^b	26.01±3.70^b	2.73±0.18^b	79.24±7.01^b
VB-M组	10	258.20±39.21^b	24.61±3.78^b	2.70±0.15^b	82.24±8.01^bc
VB-H组	10	223.78±36.22^bc	21.75±3.12^b	2.45±0.16^bcd	78.42±7.52^bc
辛伐他汀组	10	245.21±35.25^b	22.53±3.01^b	2.30±0.14^bcd	85.20±9.31^b
F		17.078^＊＊	12.941^＊＊	513.455^＊＊	27.992^＊＊

组别	n	ET-1/（ng/L）	内脂素/（μg/L）	ICAM-1/（ng/L）	NO/（μmol/L）
对照组	10	106.30±22.12	18.32±3.10	14.02±2.65	31.02±3.74
模型组	12	158.36±25.52^a	45.15±5.23^a	57.21±6.78^a	18.81±3.23^a
VB-L组	10	130.02±18.04^b	39.21±4.60^b	50.10±4.52^b	23.90±2.61^b
VB-M组	10	125.74±22.47^b	28.15±5.12^bc	37.21±4.85^bc	25.17±3.02^b
VB-H组	10	112.80±23.52^b	22.45±2.98^bcd	24.72±4.12^bcd	28.49±3.42^bc
辛伐他汀组	10	115.63±20.13^b	22.04±3.01^bcd	28.32±4.74^bcd	29.33±3.14^bc
F		7.864^＊＊	71.208^＊＊	119.643^＊＊	21.224^＊＊

毛蕊花糖苷调节HMGB1/RAGE/NF-κB信号通路对动脉粥样硬化大鼠内皮功能障碍的影响

Effect of verbascoside on endothelial dysfunction in atherosclerotic rats by regulating HMGB1/RAGE signal pathway

引用本文

RichHTML

PDF (PC)

可视化

摘要/Abstract

使用本文

图/表 7

参考文献 21

相关文章 15

编辑推荐

Metrics

本文评价

组别	n	SOD/ （U/mL）	MDA/ （μmol/L）	GSH-Px/ （U/mL）
对照组	10	234.42±18.14	2.73±0.45	601.25±23.41
模型组	12	145.47±17.25^a	4.89±0.57^a	403.58±34.70^a
VB-L组	10	169.23±17.38^b	4.05±0.42^b	454.21±29.41^b
VB-M组	10	184.25±15.02^b	3.74±0.47^b	495.23±23.21^bc
VB-H组	10	215.49±16.20^bcd	2.80±0.41^bcd	549.56±24.52^bcd
辛伐他汀组	10	213.78±14.91^bcd	2.85±0.45^bcd	556.69±27.17^bcd
F		43.803^＊＊	37.908^＊＊	75.571^＊＊

组别	n	HMGB1/ β-actin	RAGE/ β-actin	p-NF-κB p65/ NF-κB p65
对照组	10	0.39±0.12	0.20±0.05	0.19±0.01
模型组	12	0.99±0.15^a	0.63±0.06^a	0.72±0.08^a
VB-L组	10	0.82±0.12^b	0.50±0.04^b	0.64±0.05^b
VB-M组	10	0.64±0.10^bc	0.42±0.05^bc	0.49±0.05^bc
VB-H组	10	0.42±0.12^bcd	0.31±0.04^bcd	0.38±0.06^bcd
辛伐他汀组	10	0.45±0.16^bcd	0.33±0.07^bcd	0.33±0.05^bcd
F		38.143^＊＊	90.077^＊＊	137.603^＊＊

[1]	天津市医学会神经外科学分会. 颅外段颈部动脉粥样硬化性疾病外科治疗京津冀专家共识[J]. 天津医药, 2024, 52(3): 225-230.
[2]	林瑶, 刘从娜, 王世霞, 张志勇. 金合欢素调节HMGB1/TLR4信号通路对脂多糖诱导牙髓细胞凋亡的影响[J]. 天津医药, 2024, 52(12): 1238-1243.
[3]	谷巍, 张惠娜, 侯丽萍, 于敏, 程黎蓉. 脂质相关指数与糖尿病肾病相关性研究[J]. 天津医药, 2024, 52(12): 1308-1312.
[4]	张贵婷, 何超. oxLDL/β2GPⅠ/aβ2GPⅠ复合物通过TLR4/MyD88/NF-κB途径促进血管内皮细胞血管生成[J]. 天津医药, 2024, 52(11): 1131-1136.
[5]	吴美娜, 戴为正, 潘毓敦, 傅懋林, 陈晓瑜. 常规脑电图联合血清miR-146a、miR-129-5p水平检测对药物难治性癫痫的临床诊断价值[J]. 天津医药, 2024, 52(11): 1207-1210.
[6]	王生成, 李琪, 蔡潇阳, 唐咏婕. 汉防己甲素对支气管哮喘小鼠气道重塑的影响及机制探讨[J]. 天津医药, 2023, 51(9): 943-947.
[7]	左宪宏, 张婷婷, 李月琴, 赵佳琪. 沉默Salusin-β对糖尿病大鼠内皮功能障碍的影响及机制研究[J]. 天津医药, 2023, 51(5): 491-497.
[8]	黄绚丽, 秘乐, 徐宇, 王红嫚. HMGB1和RAGE在呼吸机相关性肺炎中作用的研究进展[J]. 天津医药, 2023, 51(11): 1276-1280.
[9]	朱云林, 殷广莉, 戴平涛. 颈动脉超声及血清HbA1c、FIB对急性前循环脑梗死的评估价值分析[J]. 天津医药, 2022, 50(9): 948-952.
[10]	王华, 何雄. 护心通络方通过干预CETP介导脂质代谢抗兔动脉粥样硬化的实验研究[J]. 天津医药, 2022, 50(8): 827-831.
[11]	林玉凤, 汪志云, 王雪松△. 丁苯酞下调血清脂蛋白相关磷脂酶A2改善急性大动脉#br# 粥样硬化型脑梗死患者预后的临床观察#br#[J]. 天津医药, 2022, 50(5): 544-547.
[12]	胡明哲, 陈香岩, 吴光亮, 乔利军, 蔡业锋△. 中性粒细胞淋巴细胞比值、淋巴细胞单核细胞比值与症状性颅内动脉粥样硬化性狭窄的关系#br#[J]. 天津医药, 2022, 50(5): 493-497.
[13]	黄秋阳, 王伟, 罗书, 郑文武, 冯健, 叶强, 郑舒展. PM_2.5通过TLR4破坏自噬流加重Raw264.7巨噬细胞炎症反应[J]. 天津医药, 2022, 50(11): 1139-1145.
[14]	郭丹丹, 曹丽, 张凯, 周贵明. 中老年女性颈动脉斑块发生及稳定性相关危险因素分析[J]. 天津医药, 2021, 49(7): 719-722.
[15]	许景涵, 左俊荣, 韩楚仪, 李婷婷, 金冬霞, 赵福梅, 丛洪良. PCSK9抑制剂在ox-LDL诱导HUVECs损伤中的保护作用研究[J]. 天津医药, 2021, 49(7): 683-688.