中国临床药理学杂志

积雪草酸抑制TLR4/Myd88/NF-κB通路保护同型半胱氨酸损伤心微血管内皮细胞的研究

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刘振华 ¹ , 王彦新 ¹ , 李洪禹 ¹ , 田玮 ¹ , 张馨彤 ¹ , 王新宇 ² , 韦倩 ¹

中国临床药理学杂志 | 临床与基础桥接研究 2026,42(1): 34-39

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中国临床药理学杂志 |临床与基础桥接研究 2026 , 42 (1) : 34 -39

积雪草酸抑制TLR4/Myd88/NF-κB通路保护同型半胱氨酸损伤心微血管内皮细胞的研究

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刘振华¹, 王彦新¹, 李洪禹¹, 田玮¹, 张馨彤¹, 王新宇², 韦倩¹

作者信息

^1.长春中医药大学附属第三临床医院，吉林长春 130117

^2.吉林省药品检验研究院，吉林长春 130299

通讯作者:

韦倩，主任医师，硕士生导师 Tel: （0431）89912500 E-mail: weiqian1981@163.com

作者简介:

刘振华（1985-），男，副主任医师，从事心血管疾病诊断与治疗方向的临床工作和研究

Research of asiatic acid inhibiting the TLR4/Myd88/NF-κB pathway and protecting cardiac microvascular endothelial cells damaged by homocysteine

Zhen-hua LIU¹, Yan-xin WANG¹, Hong-yu LI¹, Wei TIAN¹, Xin-tong ZHANG¹, Xin-yu WANG², Qian WEI¹

Affiliations

^1.The Third Affiliated Clinical Hospital of Changchun University of Chinese Medicine, Changchun 130117, Jilin Province, China

^2.Jilin Institute of Drug Inspection, Changchun 130299, Jilin Province, China

出版时间: 2026-01-17 doi: 10.13699/j.cnki.1001-6821.2026.01.006

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摘要

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目的

评估积雪草酸（AA）通过调控Toll样受体4/髓样分化因子88/核因子κB/ NOD样受体蛋白3（TLR4/MyD88/NF-κB/NLRP3）通路对心微血管内皮细胞（CMECs）凋亡和血管再生的影响。

方法

用同型半胱氨酸（HCY）诱导大鼠CMECs模拟构建冠心病损伤细胞模型，用细胞计数试剂盒（CCK8）法验证模型构建是否成功。将细胞分为对照组（正常培养）、模型组（造模）、积雪草酸组（造模+10 μmol·L^-1 AA）和联合组（造模+1 μg·mL^-1脂多糖+10 μmol·L^-1 AA）。用CCK8法检测细胞活力，用流式细胞术法检测细胞凋亡，用蛋白质印迹法检测凋亡相关蛋白、通路相关蛋白和血管再生相关蛋白的相对表达水平。

结果

对照组、模型组、积雪草酸组和联合组的细胞活性分别为0.92±0.01、0.61±0、0.75±0.01和0.50±0.02；细胞凋亡率分别为（4.96±0.53）%、（24.98±1.68）%、（18.22±0.96）%和（34.17±0.49）%；B细胞淋巴瘤/白血病-2相关X蛋白（Bax）的相对蛋白表达水平分别为0.12±0.01、0.63±0、0.42±0.02和0.96±0.01；Bcl-2蛋白相对表达水平分别为0.99±0.02、0.34±0.01、0.69±0.01和0.10±0.01；TLR4蛋白相对表达水平分别为0.19±0.01、0.65±0、0.41±0.01和0.84±0.01；Myd88蛋白相对表达水平分别为0.29±0.02、0.77±0、0.61±0.01和0.95±0.02；NF-κB蛋白相对表达水平分别为0.22±0.01、0.82±0.02、0.53±0.02和0.84±0.02；NLRP3蛋白相对表达水平分别为0.17±0.02、0.75±0.03、0.50±0.01和0.98±0.01；血管内皮生长因子（VEGF）蛋白相对表达水平分别为0.95±0.01、0.44±0.02、0.68±0.02和0.23±0.01；血小板-内皮细胞黏附分子（CD31）蛋白相对表达水平分别为1.01±0.01、0.44±0.02、0.58±0和0.38±0.01。模型组的上述指标与对照组比较，积雪草酸组的上述指标与模型组比较，联合用药组的上述指标与积雪草酸组比较，在统计学上差异均有统计学意义（均P<0.01）。

结论

AA能通过抑制TLR4/MyD88/NF-κB通路缓解HCY诱导的心微血管内皮细胞凋亡，促进血管再生。

关键词

积雪草酸 / 冠心病 / Toll样受体4/髓样分化因子88/核因子κB/ NOD样受体蛋白3 / 凋亡 / 血管生成

Abstract

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Objective

To evaluate the effects of centella asiatica acid (AA) on the apoptosis of cardiac microvascular endothelial cells (CMECs) and vascular regeneration by modulating the Toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa B/nucleotide-binding oligomerization domain-like receptor protein 3 (TLR4/MyD88/NF-κB/NLRP3) pathway.

Methods

The homocysteine (HCY)-induced rat CMECs were used to simulate and construct a coronary heart disease injury cell model, and the success of model construction was verified using the cell counting kit-8 (CCK8) method. The cells were divided into control group (normal culture), model group (modeling), centella asiatica acid group (modeling + 10 μmol·L^-1 AA) and combined group (modeling + 1 μg·mL^-1 lipopolysaccharide + 10 μmol·L^-1 AA). Cell viability was detected using CCK8, apoptosis was assessed by flow cytometry, and the relative expression levels of apoptosis-related proteins, pathway-related proteins and vascular regeneration-related proteins were measured by Western blot.

Results

The cell viability of control group, model group, asiatica acid group and combination group were 0.92±0.01, 0.61±0, 0.75±0.01 and 0.50±0.02, respectively; the apoptosis rates were (4.96±0.53)%, (24.98±1.68)%, (18.22±0.96)% and (34.17±0.49)%, respectively; the relative protein expression levels of B-cell lymphoma/leukemia 2-associated X protein (Bax) were 0.12±0.01, 0.63±0, 0.42±0.02 and 0.96±0.01, respectively; the relative expression levels of Bcl-2 protein were 0.99±0.02, 0.34±0.01, 0.69±0.01 and 0.10±0.01, respectively; the relative expression levels of TLR4 protein were 0.19±0.01, 0.65±0, 0.41±0.01 and 0.84±0.01, respectively; the relative expression levels of Myd88 protein were 0.29±0.02, 0.77±0, 0.61±0.01 and 0.95±0.02, respectively; the relative expression levels of NF-κ B protein were 0.22±0.01, 0.82±0.02, 0.53±0.02 and 0.84±0.02, respectively; the relative expression levels of NLRP3 protein were 0.17±0.02, 0.75±0.03, 0.50±0.01 and 0.98±0.01, respectively; the relative expression levels of vascular endothelial growth factor (VEGF) protein were 0.95±0.01, 0.44±0.02, 0.68±0.02 and 0.23±0.01, respectively; the relative expression levels of platelet endothelial cell adhesion molecule-1 (CD31) protein were 1.01±0.01, 0.44±0.02, 0.58±0 and 0.38±0.01, respectively. The above indicators of model group were compared with control group, the above indicators of the oxalic acid group were compared with the model group, and the above indicators of the combination therapy group were compared with the asiatica acid group, the differences were all statistically significant (all P<0.01).

Conclusion

AA can alleviate HCY induced apoptosis of cardiac microvascular endothelial cells and promote vascular regeneration by inhibiting TLR4/MyD88/NF-κB pathway.

Key words

asiatic acid / coronary heart disease / Toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa B/nucleotide-binding oligomerization domain-like receptor protein 3 pathway / apoptosis / angiogenesis

引用本文

刘振华, 王彦新, 李洪禹, 田玮, 张馨彤, 王新宇, 韦倩. 积雪草酸抑制TLR4/Myd88/NF-κB通路保护同型半胱氨酸损伤心微血管内皮细胞的研究. 中国临床药理学杂志, 2026 , 42 (1) : 34 -39 . DOI: 10.13699/j.cnki.1001-6821.2026.01.006

Zhen-hua LIU, Yan-xin WANG, Hong-yu LI, Wei TIAN, Xin-tong ZHANG, Xin-yu WANG, Qian WEI. Research of asiatic acid inhibiting the TLR4/Myd88/NF-κB pathway and protecting cardiac microvascular endothelial cells damaged by homocysteine[J]. Chinese Journal of Clinical Pharmacology, 2026 , 42 (1) : 34 -39 . DOI: 10.13699/j.cnki.1001-6821.2026.01.006

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2026年第42卷第1期

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doi: 10.13699/j.cnki.1001-6821.2026.01.006

接收时间：2025-05-23
首发时间：2026-08-06
出版时间：2026-01-17

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收稿日期：2025-05-23

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作者信息

^1.长春中医药大学附属第三临床医院，吉林长春 130117

^2.吉林省药品检验研究院，吉林长春 130299

通讯作者:

韦倩，主任医师，硕士生导师 Tel: （0431）89912500 E-mail: weiqian1981@163.com

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2026.01.006

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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