2023 年第 3 期 第 18 卷

沙棘黄酮对小鼠动脉粥样硬化斑块和NOD样受体蛋白3的影响及作用机制

Effect and mechanism of Hippophae rhamnoides flavone on atherosclerotic plaque and NOD-like receptor protein 3 in mice

作者：贾敏李城城王乐玲王丽妹张玲李俊红

英文作者：Jia Min Li Chengcheng Wang Yueling Wang Limei Zhang Ling Li Junhong

单位：广东省广州市胸科医院综合内科，广州510095

英文单位：Department of General Medicine Guangzhou Chest Hospital Guangdong Province Guangzhou 510095 China

关键词：沙棘黄酮；动脉粥样硬化；斑块；炎症

英文关键词：Hippophaerhamnoidesflavone;Atherosclerosis;Plaque;Inflammation

• 摘要：

• 目的 分析沙棘黄酮对小鼠动脉粥样硬化斑块和NOD样受体蛋白3（NLRP3）的影响及作用机制。方法 选取50只无特定病原体级载脂蛋白E基因敲除C57BL/6雄性小鼠，其中10只作为对照组，其余40只建立动脉粥样硬化模型。取小鼠腹主动脉显微镜下观察验证造模是否成功。将建模成功的30只小鼠，按照简单随机化法分为模型组、阿托伐他汀钙组及沙棘黄酮组，各10只。建模成功后开始给药，对照组、模型组予0.9%氯化钠注射液0.5 L灌胃，阿托伐他汀钙组予0.9%氯化钠注射液0.5 L+阿托伐他汀钙10 mg/kg灌胃，沙棘黄酮组予0.9%氯化钠注射液0.5 L+沙棘黄酮10 mg/kg灌胃，均为1次/d、连续灌胃7周。观察小鼠颈总动脉粥样硬化斑块面积、内膜中层厚度（IMT），检测血脂、血清炎症因子水平及颈总动脉组织Toll样受体4（TLR4）/白细胞介素6（IL-6）/信号转导与转录激活因子3（STAT3）通路蛋白表达量。结果 模型组斑块面积、IMT均大于对照组，阿托伐他汀钙组、沙棘黄酮组斑块面积、IMT均小于模型组，且沙棘黄酮组小于阿托伐他汀钙组［（0.24±0.09）cm2比（0.37±0.13）cm2、（0.16±0.02）mm比（0.25±0.03）mm］（均P<0.05）。模型组总胆固醇、三酰甘油、低密度脂蛋白胆固醇、血清IL-1β、IL-6、NLRP3水平及颈总动脉组织TLR4、IL-6、STAT3蛋白表达量均高于对照组，阿托伐他汀钙组、沙棘黄酮组上述指标水平均低于模型组，且沙棘黄酮组均低于阿托伐他汀钙组（均P＜0.05）；模型组高密度脂蛋白胆固醇（HDL-C）水平低于对照组，阿托伐他汀钙组、沙棘黄酮组HDL-C水平高于模型组，且沙棘黄酮组高于阿托伐他汀钙组（均P<0.05）。结论 沙棘黄酮可以减少小鼠动脉粥样硬化斑块，降低血脂及NLRP3水平，其作用机制可能与抑制TLR4/IL-6/STAT3通路有关。

• Objective  To analyze the effect and mechanism of Hippophae rhamnoides flavone on atherosclerotic plaque and NOD-like receptor protein 3 (NLRP3) in mice. Methods  Totally 50 specific pathogen free C57BL/6 male mice with apolipoprotein E gene knockout were selected. Ten of them were divided into the control group, and the remaining 40 were established as atherosclerotic model. The abdominal aorta of mice was observed under the microscope to verify whether the model was successful. Later, 30 atherosclerotic model mice were randomly divided into model group, atorvastatin calcium group and Hippophae rhamnoides flavone group, with 10 mice in each group. After successfully modeling, drug administration was started. The control group and the model group received 0.9% sodium chloride injection 0.5 L for gavage, the atorvastatin calcium group received 0.9% sodium chloride injection 0.5 L + atorvastatin calcium 10 mg/kg for gavage, and the Hippophae rhamnoides flavone group received 0.9% sodium chloride injection 0.5 L + Hippophae rhamnoides flavone 10 mg/kg for gavage, all with once a day for 7 weeks. The common carotid artery atherosclerotic plaque area and intima-media thickness (IMT) in mice were observed. Levels of blood lipid, serum inflammatory factors and the expression of Toll-like receptor 4 (TLR4)/interleukin-6 (IL-6)/signal transducer and activators of transcripton 3 (STAT3) pathway were detected. Results  The plaque area and IMT in the model group were larger than those in the control group, the plaque area and IMT in the atorvastatin calcium group and Hippophae rhamnoides flavone group were lower than those in the model group, and the two indexes in the Hippophae rhamnoides flavone group were lower than those in the atorvastatin calcium group ［（0.24±0.09）cm2 vs（0.37±0.13）cm2,（0.16±0.02）mm vs （0.25±0.03）mm］(all P<0.05). The levels of total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, surum IL-1β, IL-6, NLRP3, and expressions of TLR4, IL-6 and STAT3 protein in common carotid artery tissue in the model group were higher than those in the control group, the above indexes in the atorvastatin calcium group and Hippophae rhamnoides flavone group were lower than those in the model group, and those in the Hippophae rhamnoides flavone group were lower (all P<0.05); the level of high-density lipoprotein cholesterol (HDL-C) in the model group was lower than that in the control group, the levels of HDL-C in the atorvastatin calcium group and Hippophae rhamnoides flavone group were higher than that in the control group, and the level of HDL-C in the Hippophae rhamnoides flavone group was higher(all P<0.05). Conclusions  Hippophae rhamnoides flavone can reduce atherosclerotic plaque, and decrease levels of blood lipid and NLRP3 in mice. Its mechanism may be related to inhibit TLR4/IL-6/STAT3 pathway.