| 李建橡，马晓聪，李芳艳，吴福佳，周月，许育佳，岳桂华.黄连解毒汤调控IRE1α-XBP1-CHOP内质网应激信号通路改善SHR主动脉损伤[J].,2023,43(5):585-590 |
| 黄连解毒汤调控IRE1α-XBP1-CHOP内质网应激信号通路改善SHR主动脉损伤 |
| Huanglian Jiedu Decoction Alleviates SHR Aortic Injury via Regulating IRE1 α- XBP1-CHOP Endoplasmic Reticulum Stress Signal Pathway |
| |
| DOI：10.7661/j.cjim.20230404.012 |
| 中文关键词: 黄连解毒汤 自发性高血压 内质网应激 主动脉 IRE1α-XBP1-CHOP信号通路 中药复方 |
| 英文关键词:Huanglian Jiedu Decoction essential hypertension endoplasmic reticulum stress abdominal aorta IRE1α-XBP1-CHOP signaling pathway Chinese herbal compound |
| 基金项目:国家自然科学基金资助项目（No.81860831）；广西自然科学基金资助项目（No.2018GXNSFAA281077） |
|
| Hits: 530 |
| Download times: 290 |
| 中文摘要: |
| 目的 观察黄连解毒汤（HLJDD）对自发性高血压大鼠（SHR）通过主动脉肌醇酶1α（IRE1α）- x-框结合蛋白1（XBP1）-C/EBP同源蛋白（CHOP）介导内质网应激信号通路的影响。方法 将
50只SHR随机分为模型组、低剂量HLJDD组（7.5 g/kg）、中剂量HLJDD组（15 g/kg）、高剂量HLJDD组（30 g/kg）以及卡托普利组（0.0175 g/kg）5个组别，另设WKY大鼠为空白对照组，每组各10只。除模型组和空白对照组灌胃给予等体积的生理盐水外，其余各组分别灌胃给予相应剂量药物，每天1次，共6周。实验末，取主动脉行HE染色检测组织病理变化，TUNEL染色检测细胞凋亡，Western Blot和qPCR检测IRE1α-XBP1-CHOP通路相关蛋白和mRNA表达水平变化。结果 与空白对照组比较，模型组主动脉内膜严重脱落，中膜弹性纤维排列有一定紊乱，主动脉凋亡细胞率显著升高（P<0.05）；中、高剂量HLJDD组和卡托普利组能够有效改善组织病理现象，显著降低细胞凋亡率（P<0.05）。与空白对照组比较，模型组中内质网应激标志基因XBP1、葡萄糖调节蛋白（GRP78）、CHOP、蛋白质二硫键异构酶（PDIA6）、miR-322表达升高（P<0.05）；eNOS表达降低（P<0.05）。与模型组比较，不同剂量HLJDD及卡托普利干预后，XBP1、GRP78、CHOP、PDIA6、IRE1α、miR-322表达降低（P<0.05），内皮型一氧化氮合酶（eNOS）表达升高（P<0.05）。结论 HLJDD能够有效改善SHR主动脉组织损伤的作用机制可能与调控IRE1α-XBP1-CHOP介导内质网应激信号传导途径有关。 |
| 英文摘要: |
| Objective To observe the effect of Huanglian Jiedu Decoction（HLJDD）on the endoplasmic reticulum stress signaling pathway mediated by inositol-requiring enzyme 1α- X-box binding protein 1-C/EBP homologous protein（IRE1α -XBP1-CHOP） in spontaneous hypertension rats（SHR）. Methods Totally 50 SHR were randomly divided into model group，low-dose HLJDD group （7.5 g·kg-1），medium-dose HLJDD group （15 g·kg-1），high-dose HLJDD group （30 g·kg-1）and captopril group （0.0175 g·kg-1），and the WKY rats were selected as the blank control group，with 10 in each group. Except for the equal volume of physiological saline given to the stomach in the model group and the blank control group，the other groups were given the corresponding doses of drugs once a day for a total of 6 weeks. At the end of the experiment，aortic HE staining was used to detect histopathological changes，TUNEL staining was used to detect apoptosis，and Western Blot and qPCR were used to detect changes in IRE1α-XBP1-CHOP pathway-related proteins and mRNA expression levels. Results Compared with the blank control group，the aortic endometrium in the model group was seriously detached，the middle membrane elastic fiber arrangement was disordered to a certain extent，and the aortic apoptosis cell rate increased significantly（P<0.05）. The medium and high-dose HLJDD groups and captopril group could effectively alleviate histopathological phenomena and significantly reduce the apoptosis rate（P<0.05）. Compared with the blank control group，the expression of the endoplasmic reticulum stress marker genes XBP1，glucose regulated protein（GRP78），CHOP，protein disulfide isomerase A6（PDIA6），miR-322 in the model group increased （P<0.05）； the expression of endothelial nitric oxide synthase（eNOS） decreased （P<0.05）.Compared with the model group，after different doses of HLJDD and captopril intervention，the expressions of XBP1，GRP78，CHOP，PDIA6，IRE1α，miR-322 decreased to a certain extent （P<0.05），and eNOS expression increased （P<0.05）. Conclusion The mechanism of action that HLJDD can effectively alleviate SHR aortic tissue injury may be related to the regulation of IRE1α-XBP1-CHOP mediated endoplasmic reticulum stress signal transmission. |
| View Full Text View/Add Comment Download reader |
