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李钰佳,李定祥,张熙,彭珣,刘春华,邓奕辉.基于AGEs/RAGE/NF-κB通路探讨左归降糖通脉方对大鼠脑微血管内皮细胞损伤的保护作用[J].湖南中医药大学学报英文版,2022,42(7):1057-1063.[Click to copy
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| 基于AGEs/RAGE/NF-κB通路探讨左归降糖通脉方对大鼠脑微血管内皮细胞损伤的保护作用 |
| 李钰佳,李定祥,张熙,彭珣,刘春华,邓奕辉 |
| (湖南中医药大学, 湖南 长沙 410208;湖南省第二人民医院, 湖南 长沙 410035) |
| 摘要: |
| 目的 观察左归降糖通脉方对晚期糖基化终末产物（advanced glycation end products,AGEs）诱导大鼠脑微血管内皮细胞（brain microvascular endothelial cells,BMECs）损伤的干预作用，并基于AGEs/RAGE/NF-κB通路探讨左归降糖通脉方的作用机制。方法 将30只SD大鼠随机均分为空白组（同体积蒸馏水）、中药组[左归降糖通脉方36 g/(kg·d)]和西药组[尼莫地平18.35 mg/(kg·d)+格列齐特27.5 mg/(kg·d)]，每日灌胃1次，连续5 d，用于制备含药血清。将BMECs随机分为空白组、模型组、左归降糖通脉方组、尼莫地平+格列齐特组、晚期糖基化终末产物受体（receptor for advanced glycation end products,RAGE）抑制剂(FPS-ZM1)组及吡咯烷二硫代氨基甲酸铵（pyrrolidinedithiocarbamate ammonium,PDTC）组，BMECs加入200 mg/L的AGEs作用24 h后，分别予空白血清、空白血清、左归降糖通脉方含药血清、尼莫地平+格列齐特含药血清、FPS-ZM1、PDTC干预。通过形态学观察及CCK-8法检测细胞存活率，采用Western blot、RT-PCR法检测RAGE、核因子κB（nuclear factor kappa-B,NF-κB）的蛋白和mRNA表达情况。结果 与空白组比较，模型组细胞存活率明显下降（P＜0.01）；与模型组比较，左归降糖通脉方组及尼莫地平+格列齐特组细胞存活率上升（P＜0.05）；相较于空白组，模型组RAGE、NF-κB的蛋白和mRNA表达水平明显上调（P＜0.01）；相较于模型组，左归降糖通脉方组、尼莫地平+格列齐特组、FPS-ZM1组及PDTC组RAGE、NF-κB的蛋白和mRNA表达水平明显下调（P＜0.05）；左归降糖通脉方组与FPS-ZM1组RAGE、NF-κB的蛋白和mRNA表达差异无统计学意义（P＞0.05）。结论 左归降糖通脉方可能通过抑制AGEs与RAGE的结合，抑制AGEs/RAGE/NF-κB通路的激活，下调下游炎症因子的释放，对BMECs起到保护作用。 |
| 关键词: 糖尿病血管并发症 糖基化终末产物 左归降糖通脉方 脑微血管内皮细胞 核因子κB |
| DOI：10.3969/j.issn.1674-070X.2022.07.001 |
| Received:June 30, 2021 |
| 基金项目:国家自然科学基金项目（81874416）；湖南省中医药科研计划项目（201947）；湖南省教育厅科学研究项目（16K063）。 |
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| Effect of Zuogui Jiangtang Tongmai Formula on brain microvascular endothelial cells injury in rats based on AGEs/RAGE/NF-κB signaling pathway |
| LI Yujia,LI Dingxiang,ZHANG Xi,PENG Xun,LIU Chunhua,DENG Yihui |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;The Second People's Hospital of Hunan Province, Changsha, Hunan 410035, China) |
| Abstract: |
| Objective To observe the therapeutic effect of Zuogui Jiangtang Tongmai Formula (ZGJTTMF) on the injury of rat brain microvascular endothelial cells (BMECs) induced by advanced glycation end products (AGEs), and to explore the mechanism of ZGJTTMF based on the AGEs/RAGE/NF-κB signaling pathway. Methods A total of 30 rats were randomly divided into blank group (the same volume of distilled water), Chinese medicine group[ZGJTTMF 36 g/(kg·d)] and western medicine group[nimodipine 18.35 mg/(kg·d) and gliclazide 27.5 mg/(kg·d)]. The rats were used to prepare medicated serum by gavage, once a day for 5 d. BMECs were divided into blank group, model group, ZGJTTMF group, nimodipine+gliclazide group, receptor for advanced glycation end products inhibitor (FPS-ZM1) group and pyrrolidinedithiocarbamate ammonium (PDTC) group. After adding 200 mg/L of AGEs to BMECs for 24 h, blank serum, blank serum, ZGJTTMF medicated serum, nimodipine+gliclazide medicated serum, FPS-ZM1 and PDTC were added. The cell survival rate was detected by morphological observation and CCK-8. Western blot and RT-PCR were used to detect the protein and mRNA expression of RAGE and nuclear factor kappa-B (NF-κB) in each group. Results Compared with the blank group, the cell survival rate of the model group was significantly decreased (P<0.01); compared with the model group, the cell survival rate of ZGJTTMF group and nimodipine+gliclazide group was increased (P<0.05). Compared with the blank group, the protein and mRNA expression levels of RAGE and NF-κB were significantly increased in the model group (P<0.01); compared with the model group, the protein and mRNA expression levels of RAGE and NF-κB were significantly decreased in ZGJTTMF group, nimodipine+gliclazide group, FPS-ZM1 group and PDTC group (P<0.05); there was no significant difference in the protein and mRNA expression levels of RAGE and NF-κB between ZGJTTMF group and FPS-ZM1 group. Conclusion ZGJTTMF may protect BMECs by inhibiting the binding of AGEs and RAGE, inhibiting the activation of AGEs/RAGE/NF-κB pathway, and down-regulating the release of downstream inflammatory factors. |
| Key words: diabetic vascular complications advanced glycation end products Zuogui Jiangtang Tongmai Formula brain microvascular endothelial cells nuclear factor kappa-B |
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