Angiotensin-(1-7) Restores Microcirculation Profiles in Acute Pancreatitis Secret of Telomerase Reverse Transcriptase
Angiotensin-(1-7) Restores Microcirculation Profiles in Acute Pancreatitis Secret of Telomerase Reverse Transcriptase
复制标题
血管紧张素-(1-7) 恢复急性胰腺炎的微循环状况
DOI：
10.1097/mpa.0000000000002139
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发表时间：
2022-09-01
期刊：
影响因子：
2.9
通讯作者：
Yin，Chenghong
中科院分区：
文献类型：
--
作者：
Wang，Xueyan;Cui，Tianyu;Yin，Chenghong
目的探讨血管紧张素（Ang）-（1-7）介导的胰腺微循环和内皮损伤的恢复是否与端粒酶逆转录酶（TERT）的表达有关。胰腺炎通过组织病理学和血清淀粉酶水平证实。激光多普勒检测胰腺微循环功能。采用脂多糖（LPS）诱导内皮细胞损伤模型。采用酶联免疫吸附法检测促炎细胞因子，transwell法检测内皮细胞通透性，共聚焦显微镜检测线粒体功能障碍和线粒体活性氧（mtROS）水平。此外，Ang-（1-7）通过抑制内皮细胞通透性的增加和以TERT依赖的方式释放促炎细胞因子来保护内皮细胞免受损伤。此外，TERT参与Ang-（1-7）介导的LPS诱导的内皮细胞线粒体功能障碍和线粒体ROS的衰减。ConclusionsAngiotensin-（1-7）通过抑制线粒体ROS的产生和线粒体功能障碍，以TERT依赖的方式恢复胰腺微循环，逆转内皮损伤。
ObjectivesThe aim of this study was to investigate whether angiotensin (Ang)-(1–7)–mediated restoration of pancreatic microcirculation profiles and endothelial injury is associated with the expression of telomerase reverse transcriptase (TERT).MethodsWild-type, TERT transgene, and TERT knockdown mice were used in this study, and acute pancreatitis model was induced by intraperitoneal injection of cerulein and lipopolysaccharide (LPS). Pancreatitis was confirmed by histopathology and serum amylase levels. Pancreatic microcirculation function was assessed by laser Doppler. Endothelial injury model was established by exposing endothelial cells to LPS. Proinflammatory cytokines were detected using enzyme-linked immunosorbent assay, endothelial permeability was detected using transwell assay, and mitochondrial dysfunction and mitochondrial reactive oxygen species (mtROS) were determined by performing confocal microscopy.ResultsThe effects of Ang-(1–7) in the treatment of pancreatic microcirculation dysfunction were associated with TERT expression. In addition, Ang-(1–7) protected against endothelial cell lesions via inhibiting the increase in endothelial cell permeability and release of proinflammatory cytokines in a TERT-dependent manner. Furthermore, TERT was involved in Ang-(1–7)–mediated attenuation of mitochondrial dysfunction and mtROS in LPS-induced endothelial cells.ConclusionsAngiotensin-(1–7) restores pancreatic microcirculation profiles and reverses endothelial injury by inhibiting mtROS production and mitochondrial dysfunction in a TERT-dependent manner.