| 引用本文: |
卿俊, 刘平安, 鄢然, 刘慧萍, 雷晓明, 黄家威, 管聘, 刘惠敏, 刘婷, 唐佳倩, 张国民.天麻钩藤饮对自发性高血压大鼠血管重塑的抑制作用及对NOX2/ROS通路、内质网应激的影响[J].湖南中医药大学学报,2024,44(12):2150-2156[点击复制] |
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| 天麻钩藤饮对自发性高血压大鼠血管重塑的抑制作用及对NOX2/ROS通路、内质网应激的影响 |
| 卿俊,刘平安,鄢然,刘慧萍,雷晓明,黄家威,管聘,刘惠敏,刘婷,唐佳倩,张国民 |
| (湖南中医药大学, 湖南 长沙 410208;湖南省中西医结合医院, 湖南 长沙 410006;南宁市中医医院, 广西 南宁 530000;湖南中医药大学第一附属医院, 湖南 长沙 410007) |
| 摘要: |
| 目的 研究天麻钩藤饮对自发性高血压大鼠（spontaneously hypertensive rats,SHR）血管重塑的抑制作用及机制。方法 将大鼠随机分为正常对照组、模型组、厄贝沙坦组和天麻钩藤饮组。给药过程中每周测量大鼠尾动脉压；给药4周后，HE染色检测胸主动脉组织情况，测量与计算内膜-中层厚度（intima-media thickness,IMT）、内膜-中层厚度/管腔直径（lumen diameter,LD），同时扫描电镜检查组织形态变化；免疫组织化学测定NADPH氧化酶2（NADPH oxidase 2,NOX2）、C/EBP同源蛋白（C/EBP homologous protein,CHOP）、葡萄糖调节蛋白78（glucose-regulating protein 78,GRP78）蛋白的表达情况；ELISA测定血浆中活性氧（reactive oxygen species,ROS）含量。结果 （1）尾动脉压检测：与正常对照组比较，模型组大鼠收缩压均显著升高（P<0.05）；与模型组比较，给药第1周起各治疗组大鼠收缩压均下降（P<0.05）。（2）胸主动脉组织形态学检测：扫描电镜可见模型组胸主动脉壁较正常对照组明显增厚；与模型组比较，各治疗组胸主动脉壁厚度均降低。HE染色观察可见正常对照组胸主动脉血管结构正常，未见动脉管壁增生；模型组胸主动脉壁明显增厚，单位面积细胞核数量增多；与模型组比较，各治疗组胸主动脉壁厚度、单位面积细胞核数量均减少。与正常对照组比较，模型组胸主动脉IMT、IMT/LD增加（P<0.05）；与模型组比较，各治疗组胸主动脉IMT、IMT/LD下降（P<0.05）。（3）免疫组织化学检测胸主动脉中NOX2、CHOP、GRP78蛋白表达水平：与正常对照组比较，模型组血管壁NOX2、CHOP、GRP78蛋白表达水平显著上升（P<0.05）；与模型组比较，各治疗组血管壁NOX2、CHOP、GRP78蛋白表达均下降（P<0.05）。（4）ELISA测定血浆中ROS含量：与正常对照组比较，模型组大鼠血浆中ROS含量显著上升（P<0.05）；与模型组比较，各治疗组ROS含量显著下降（P<0.05）。结论 天麻钩藤饮在降压的同时抑制血管重塑，其机制可能与抑制NOX2/ROS通路介导的内质网应激有关。 |
| 关键词: 天麻钩藤饮 高血压 血管重塑 NOX2/ROS通路 内质网应激 |
| DOI：10.3969/j.issn.1674-070X.2024.12.002 |
| 投稿时间：2024-05-24 |
| 基金项目:国家自然科学基金面上项目（81973920）;湖南省中医药研究院一般课题（202025）;湖南省教育厅科学研究青年项目（21B0378）;湖南省自然科学基金-医卫行业联合基金项目（2024JJ9466）;湖南省中医药科研计划重点项目（E2022007）;湖南省教育厅科学研究重点项目（22A0260）;湖南省研究生科研创新项目（CX20220821，CX20230836，CX20230827）;湖南中医药大学研究生科研创新项目（2023CX111，20213747）;长沙市2022年度指导性科技计划项目（kzd22005）;湖南省教育厅科学研究项目（20A385）。 |
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| Inhibitory effects of Tianma Gouteng Drink on vascular remodeling and its impact on NOX2/ROS pathway and endoplasmic reticulum stress in SHR |
| QING Jun, LIU Ping'an, YAN Ran, LIU Huiping, LEI Xiaoming, HUANG Jiawei, GUAN Pin, LIU Huimin, LIU Ting, TANG Jiaqian, ZHANG Guomin |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Hunan Provincial Hospital of Integrated Chinese and Western Medicine, Changsha, Hunan 410006, China;Nanning Hospital of Traditional Chinese Medicine, Nanning, Guangxi 530000, China;The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China) |
| Abstract: |
| Objective To explore the inhibitory effects and related mechanism of Tianma Gouteng Drink on vascular remodeling in spontaneously hypertensive rats (SHR). Methods The rats were randomized into normal control, model, irbesartan, and Tianma Gouteng Drink groups. The rat tail artery pressure was measured weekly during administration. After 4 weeks of administration, the tissue of the thoracic aorta was examined by HE staining; intima-media thickness (IMT) of the thoracic aorta was measured and the IMT/lumen diameter (LD) ratio was calculated; the morphological changes of the thoracic aorta were examined by scanning electron microscopy. Immunohistochemical analysis was performed to determine the protein expressions of NADPH oxidase 2 (NOX2), C/EBP homologous protein (CHOP), and glucose-regulating protein 78 (GRP78) in the thoracic aorta. ELISA was used to determine the plasma levels of reactive oxygen species (ROS). Results (1) Tail artery pressure measurement: Compared with normal control group, the systolic blood pressure of rats in model group was significantly higher (P<0.05); compared with model group, the systolic blood pressure of rats in all treatment groups decreased from the first week of administration (P<0.05). (2) Histomorphological examination of the thoracic aorta: Scanning electron microscopy revealed that the wall of the thoracic aorta in model group was significantly thicker than that in normal control group; compared with model group, the thickness of the thoracic aortic wall was reduced in all treatment groups. HE staining showed that the vascular structure of the thoracic aorta in normal control group was normal, with no evidence of arterial wall proliferation; in model group, the wall of the thoracic aorta was significantly thickened, and the number of nuclei per unit area increased; compared with model group, both the thickness of the thoracic aortic wall and the number of nuclei per unit area were reduced in all treatment groups. Compared with normal control group, the IMT and IMT/LD of the thoracic aorta in model group increased (P<0.05); compared with model group, the IMT and IMT/LD of the thoracic aorta decreased in all treatment groups (P<0.05). (3) Immunohistochemical determination of NOX2, CHOP, and GRP78 protein expression levels in the thoracic aorta: Compared with normal control group, the protein expression levels of NOX2, CHOP, and GRP78 in the vascular wall of model group were significantly higher (P<0.05); compared with model group, the protein expression levels of NOX2, CHOP, and GRP78 in the vascular wall decreased in all treatment groups (P<0.05). (4) ELISA measurement of plasma ROS level: Compared with normal control group, plasma ROS level in model group significantly increased (P<0.05); compared with model group, ROS levels of all treatment groups significantly decreased (P<0.05). Conclusion Tianma Gouteng Drink can inhibit vascular remodeling while lowering blood pressure, and its mechanism may be related to the inhibition of endoplasmic reticulum stress mediated by NOX2/ROS pathway. |
| Key words: Tianma Gouteng Drink hypertension vascular remodeling NADPH oxidase 2/reactive oxygen species pathway endoplasmic reticulum stress |
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