| 王 欢,吴 燕,刘 洋,郝 翔,肖懿慧.毛蕊异黄酮通过JAK2/STAT3信号通路抑制大鼠动脉粥样硬化[J].,2022,(24):4618-4626 |
| 毛蕊异黄酮通过JAK2/STAT3信号通路抑制大鼠动脉粥样硬化 |
| Calycoin Inhibits Rat Atherosclerosis through JAK2/STAT3 Signaling Pathway |
| 投稿时间：2022-05-23 修订日期：2022-06-18 |
| DOI：10.13241/j.cnki.pmb.2022.24.004 |
| 中文关键词: 动脉粥样硬化 毛蕊异黄酮 血管平滑肌细胞 表型转化 AK2/STAT3信号通路 血脂代谢 氧化应激 |
| 英文关键词: Atherosclerosis Calycoin Vascular smooth muscle cells Phenotypic transformation AK2/STAT3 signaling pathway Lipid metabolism Oxidative stress |
| 基金项目:国家自然科学基金青年项目（82000414）；西安交通大学第一附属医院院基金（YK201516） |
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| 中文摘要: |
| 摘要 目的：探究毛蕊异黄酮（CA）治疗动脉粥样硬化（AS）的作用及其机制。方法：将10只未建模和给药的Wistar大鼠作为对照组（Control组），50只AS建模Wistar大鼠随机分为AS模型组（AS组）、低剂量CA组（L-CA组，10 mg/kg）、中剂量CA组（M-CA组，50 mg/kg）、高剂量CA组（H-CA组，100 mg/kg）和阳性药物辛伐他汀组（Sim组，2 mg/kg），每组10只。每天给药1次，连续4周。通过苏木精伊红（HE）染色观察大鼠胸主动脉组织的病理变化。按照试剂盒说明书测定各组大鼠血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、丙二醛（MDA）和超氧化物歧化酶（SOD）水平。将大鼠血管平滑肌细胞（VSMC）分为6组，Control组、血管紧张素Ⅱ（Ang Ⅱ）组（10-6 mmol/L Ang Ⅱ）、Ang Ⅱ+0.1 CA组（10-6 mmol/L Ang Ⅱ+0.1 mg/L CA）、Ang Ⅱ+1 CA组（10-6 mmol/L Ang Ⅱ+1 mg/L CA）、Ang Ⅱ+10 CA组（10-6 mmol/L Ang Ⅱ+10 mg/L CA）、Ang Ⅱ+1 CA+AG490（10-6 mmol/L Ang Ⅱ+50 μmol/L AG490）组。通过CCK-8法和EdU染色测定VSMC的增殖，Transwell测定VSMC的迁移。通过免疫荧光染色检测VSMC中的α-平滑肌肌动蛋白（α-SMA）表达。通过Western blot检测大鼠胸主动脉组织和VSMC中的α-SMA、骨桥蛋白（OPN）、JAK2、p-JAK2、STAT3、p-STAT3的蛋白表达。结果：L-CA组、M-CA组、H-CA组和Sim组大鼠胸主动脉的病变均较AS组减轻，其中H-CA组和Sim组形态改善最明显。与AS组相比，M-CA组、H-CA组和Sim组大鼠的血清中TC、TG、LDL-C和MDA水平降低（P<0.05），血清HDL-C和SOD水平升高，胸主动脉组织中的α-SMA蛋白表达水平升高（P<0.05），OPN的蛋白表达水平及JAK2和STAT3的蛋白磷酸化水平降低（P<0.05）。与Ang Ⅱ组相比，Ang Ⅱ+1 CA组、Ang Ⅱ+10 CA组和Ang Ⅱ+1 CA+AG490组的相对细胞活力和EdU阳性率降低（P<0.05），迁移细胞数降低（P<0.05），α-SMA相对荧光强度和蛋白表达水平升高（P<0.05），OPN的蛋白表达水平及JAK2和STAT3的蛋白磷酸化水平降低（P<0.05）。结论：CA可减轻AS大鼠的胸主动脉病变、纠正血脂代谢和氧化应激失衡，其机制可能与CA对VSMC表型转化和JAK2/STAT3信号通路的抑制有关。 |
| 英文摘要: |
| ABSTRACT Objective: To reveal the effect and mechanism of calycoin (CA) in the treatment of atherosclerosis (AS). Methods: 10 unmodeled and administered Wistar rats were used as control group (Control group), and 50 AS modeled Wistar rats were randomly divided into AS model group (AS group), low-dose CA group (L-CA group, 10 mg /kg), middle-dose CA group (M-CA group, 50 mg/kg), high-dose CA group (H-CA group, 100 mg/kg) and positive drug simvastatin group (Sim group, 2 mg/kg) ), 10 in each group. Administer once a day for 4 consecutive weeks. The pathological changes of rat thoracic aorta were observed by hematoxylin and eosin (HE) staining. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined according to the kit instructions. Rat vascular smooth muscle cells (VSMC) were divided into 6 groups: Control group, angiotensin Ⅱ (Ang Ⅱ) group (10-6 mmol/L Ang Ⅱ), Ang Ⅱ+0.1 CA group (10-6 mmol/L Ang Ⅱ+0.1 mg/L CA), Ang Ⅱ+1 CA group (10-6 mmol/L Ang Ⅱ+1 mg/L CA), Ang Ⅱ+10 CA group (10-6 mmol/L Ang Ⅱ+10 mg/L CA), Ang Ⅱ+1 CA+AG490 group (10-6 mmol/L Ang Ⅱ+50 μmol/L AG490). The proliferation of VSMC was measured by CCK-8 method and EdU staining, and the migration of VSMC was measured by Transwell. α-smooth muscle actin (α-SMA) expression in VSMC was detected by immunofluorescence staining. The protein expressions of α-SMA, osteopontin (OPN), JAK2, p-JAK2, STAT3 and p-STAT3 in rat thoracic aorta tissue and VSMC were detected by Western blot. Results: The lesions of rat thoracic aorta on L-CA group, M-CA group, H-CA group and Sim group were all relieved compared with AS group, and the morphology of H-CA group and Sim group improved most obviously. Compared with AS group, serum TC, TG, LDL-C and MDA levels were decreased in M-CA group, H-CA group and Sim group, serum HDL-C and SOD levels were increased, the expression level of α-SMA protein increased, the protein expression level of OPN and the protein phosphorylation levels of JAK2 and STAT3 decreased (P<0.05). Compared with Ang Ⅱ group, the relative cell viability and EdU positive rate of Ang Ⅱ+1 CA group, Ang Ⅱ+10 CA group and Ang Ⅱ+1 CA+AG490 group decreased (P<0.05), the number of migrating cells decreased (P<0.05), the relative fluorescence intensity and protein expression level of α-SMA increased (P<0.05), the protein expression level of OPN and the protein phosphorylation levels of JAK2 and STAT3 were decreased (P<0.05). Conclusion: CA can alleviate thoracic aortic lesions, correct the imbalance of blood lipid metabolism and oxidative stress in AS rats, and the mechanism may be related to the inhibition of VSMC phenotype transformation and JAK2/STAT3 signaling pathway by CA. |
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