Department of Gastroenterology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Department of Intensive Care Unit, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Biomed Res Int. 2022 Aug 26;2022:4710993. doi: 10.1155/2022/4710993. eCollection 2022.
In mice with liver fibrosis produced by carbon tetrachloride (CCl), the effects of olmesartan on intrahepatic angiogenesis and sinusoidal remodeling will be evaluated.
By injecting CCl into the peritoneal cavity, we established a mouse model of liver fibrosis. Using Sirius red and Masson trichrome staining, the extent of liver fibrosis in the animals was determined. Using immunohistochemical labeling and western blotting, the level of -smooth muscle actin (-SMA) expression, a characteristic of hepatic stellate cell activation, was assessed. Electron microscopy was used to determine the effect of olmesartan on hepatic sinusoidal capillarization, and immunohistochemical labeling was used to determine the expression levels of endothelial and basement membrane proteins in mouse liver tissues. Platelet-derived growth factor (PDGF), IL-10, vascular endothelial growth factor (VEGF), and angiotensin II levels in mouse serum were measured by Luminex multifactor analysis and ELISA. Olmesartan's effect on the angiotensin II type 1 receptor (AT1R) and the VEGF receptor (VEGFR) was evaluated using western blotting.
Olmesartan reduced CCl-induced inflammatory cell infiltration and collagen deposition to alleviate liver fibrosis. -SMA expression was decreased, and HSC activation was inhibited in mouse liver tissues by olmesartan treatment. In addition, hepatic sinusoidal capillarization was improved under the action of olmesartan. The expression of collagen IV, fibronectin, CD31, and von Willebrand factor (VWF) in the olmesartan group was also markedly downregulated. In fibrotic mice, olmesartan medication decreased the levels of PDGF, VEGF, and angiotensin II, but it increased the level of IL-10. Moreover, olmesartan reduced the expression of VEGFR-1, VEGFR-2, and AT1R relative to CCl-induced liver fibrosis.
In mice with CCl-induced fibrosis, olmesartan lowers angiogenesis and improves hepatic sinusoidal remodeling, according to our findings. By acting on the angiotensin II-AT1R-VEGF axis, this is achieved.
在四氯化碳（CCl）诱导的肝纤维化小鼠模型中，评估奥美沙坦对肝内血管生成和肝窦重构的影响。
通过腹腔注射 CCl 建立小鼠肝纤维化模型。采用天狼猩红和 Masson 三色染色法确定动物肝纤维化程度。采用免疫组化标记和 Western blot 检测 -平滑肌肌动蛋白（-SMA）的表达水平，-SMA 是肝星状细胞活化的特征。电子显微镜用于评估奥美沙坦对肝窦毛细血管化的影响，免疫组化标记用于检测小鼠肝组织中内皮和基底膜蛋白的表达水平。采用 Luminex 多因子分析和 ELISA 法测定小鼠血清中血小板衍生生长因子（PDGF）、白细胞介素 10（IL-10）、血管内皮生长因子（VEGF）和血管紧张素 II 水平。采用 Western blot 评估奥美沙坦对血管紧张素 II 型 1 受体（AT1R）和血管内皮生长因子受体（VEGFR）的作用。
奥美沙坦减轻了 CCl 诱导的炎症细胞浸润和胶原沉积，从而缓解肝纤维化。奥美沙坦治疗可降低肝组织中 -SMA 的表达，抑制肝星状细胞活化。此外，奥美沙坦可改善肝窦毛细血管化。胶原 IV、纤维连接蛋白、CD31 和血管性血友病因子（VWF）在奥美沙坦组的表达也明显下调。在纤维化小鼠中，奥美沙坦降低了 PDGF、VEGF 和血管紧张素 II 的水平，但增加了 IL-10 的水平。此外，奥美沙坦降低了 VEGFR-1、VEGFR-2 和 AT1R 的表达，与 CCl 诱导的肝纤维化相比。
根据我们的研究结果，在 CCl 诱导的纤维化小鼠中，奥美沙坦降低了血管生成并改善了肝窦重构。这是通过作用于血管紧张素 II-AT1R-VEGF 轴来实现的。
