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辽宁中医药大学中医脏象理论及应用教育部重点实验室,沈阳 110847
Received:14 December 2023,
Revised:2024-05-24,
Accepted:24 May 2024,
Published:30 June 2024
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赵娜,隋国媛,孟嘉伟,等.基于EETs介导的细胞焦亡探讨化瘀祛痰方对ApoE-/-小鼠动脉粥样硬化的影响[J].中国药房,2024,35(12):1437-1442.
ZHAO Na,SUI Guoyuan,MENG Jiawei,et al.Exploration of the effects of Huayu qutan formula on atherosclerosis in ApoE-/- mice based on EETs-mediated pyroptosis[J].ZHONGGUO YAOFANG,2024,35(12):1437-1442.
赵娜,隋国媛,孟嘉伟,等.基于EETs介导的细胞焦亡探讨化瘀祛痰方对ApoE-/-小鼠动脉粥样硬化的影响[J].中国药房,2024,35(12):1437-1442. DOI: 10.6039/j.issn.1001-0408.2024.12.05.
ZHAO Na,SUI Guoyuan,MENG Jiawei,et al.Exploration of the effects of Huayu qutan formula on atherosclerosis in ApoE-/- mice based on EETs-mediated pyroptosis[J].ZHONGGUO YAOFANG,2024,35(12):1437-1442. DOI: 10.6039/j.issn.1001-0408.2024.12.05.
目的
2
探讨化瘀祛痰方对ApoE
-/-
小鼠动脉粥样硬化(AS)的影响及机制。
方法
2
将30只ApoE
-/-
小鼠随机分为模型组、化瘀祛痰方组[20 g/(kg·d)
]
和瑞舒伐他汀组[1.55 mg/(kg·d)
]
,每组10只,另取10只C57BL/6J小鼠作为正常对照组。ApoE
-/-
小鼠喂饲高脂饲料12周复制AS模型。造模成功后,各组小鼠灌胃相应药物或生理盐水,每日1次,连续4周。末次给药后,检测各组小鼠血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、5,6-环氧二十碳三烯酸(5,6-EET)、8,9-EET、11,12-EET、14,15-EET、白细胞介素1β(IL-1β)、IL-18水平,主动脉组织中核因子κB抑制蛋白(IκB)、核因子κB(NF-κB)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、胱天蛋白酶1(Caspase-1)、IL-1β、IL-18 mRNA表达水平和IκB、NF-κB、NLRP3、凋亡相关斑点样蛋白质(ASC)、Caspase-1、消皮素D(GSDMD)、IL-1β、IL-18蛋白表达水平,并观察主动脉组织形态学变化。
结果
2
与模型组比较,化瘀祛痰方组及瑞舒伐他汀组小鼠血清中TC、TG、LDL-C、IL-1β、IL-18水平,主动脉组织中IκB、NF-κB、NLRP3、Caspase-1、IL-1β、IL-18 mRNA表达水平以及IκB、NF-κB、NLRP3、ASC、Caspase-1、GSDMD、IL-1β、IL-18蛋白表达水平均显著降低(
P
<0.05),血清中5,6-EET、8,9-EET、11,12-EET、14,15-EET水平均显著升高(
P
<0.05);主动脉粥样斑块明显减少。
结论
2
化瘀祛痰方可能通过EETs介导细胞焦亡发挥抗AS作用。
OBJECTIVE
2
To explore the effects and mechanism of Huayu qutan formula on atherosclerosis (AS) in ApoE
-/-
mice.
METHODS
2
Thirty ApoE
-/-
mice were randomly divided into model group, Huayu qutan formula group [20 g/(kg·d)
]
, rosuvastatin group [1.55 mg/(kg·d)
]
, with 10 mice in each group. Another 10 C57BL/6J mice were selected as normal control group. ApoE
-/-
mice were given high-lipid diet for 12 weeks to induce AS model. After modeling, each group was given relevant medicine or normal saline intragastrically, once a day, for 4 consecutive weeks. After the last administration, the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), 5,6-epoxyeicosatrienoic acid (5, 6-EET), 8,9-EET, 11,12-EET, 14,15-EET, interleukin-1β (IL-1β) and IL-18 in serum were detected; mRNA expressions of inhibitor of nuclear factor κB (IκB), nuclear factor κB (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Caspase-1, IL-1β and IL-18 in the aortic tissue of mice were detected; protein expression levels of IκB, NF-κB, NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), Caspase-1, gasdermin D (GSDMD), IL-1β and IL-18 in the aortic tissue of mice were detected. The morphological changes of the aortic tissue were observed.
RESULTS
2
Compared with model group, the serum levels of TC, TG, LDL-C, IL-1β and IL-18, the mRNA expressions of IκB, NF-κB, NLRP3, Caspase-1, IL-1β and IL-18 in aortic tissue, and the protein expressions of IκB, NF-κB, NLRP3, ASC, Caspase-1, GSDMD, IL-1β and IL-18 were all decreased significantly in Huayu qutan formula group and rosuvastatin group (
P
<0.05), while the serum levels of 5,6-EET, 8,9-EET, 11,12-EET and 14,15-EET were increased significantly (
P
<0.05). The aortic atherosclerotic plaques were alleviated significantly.
CONCLUSIONS
2
Huayu qutan formula can play role of anti-AS through EETs-mediated pyroptosis.
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