Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats.
Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats.
复制标题
塞来昔布和奥曲肽通过抑制肝硬化大鼠的血管生成协同改善门静脉高压
DOI：
10.1007/s10456-016-9522-9
复制
发表时间：
2016-10
期刊：
影响因子：
9.8
通讯作者：
Tang, Cheng-Wei
中科院分区：
文献类型：
--
作者：
Gao, Jin-Hang;Wen, Shi-Lei;Feng, Shi;Yang, Wen-Juan;Lu, Yao-Yao;Tong, Huan;Liu, Rui;Tang, Shi-Hang;Huang, Zhi-Yin;Tang, Ying-Mei;Yang, Jin-Hui;Xie, Hui-Qi;Tang, Cheng-Wei
关键词：
血管生成异常是肝硬变门脉高压的重要原因。除了病因治疗外，还没有探索出有效的药物或治疗方案来治疗血管生成开始或压倒性的早期肝硬变。在这项研究中，我们探索了一种通过非细胞毒性药物奥曲肽和塞来昔布来治疗早期肝硬变门脉高压症动物模型的抗血管生成作用。采用硫代乙酰胺(TAA)诱导大鼠肝硬变模型。塞来昔布和奥曲肽联合治疗可减轻肝纤维化、门静脉压力、微小肝动-门静脉瘘、肝内和内脏血管生成。塞来昔布和奥曲肽通过环氧合酶-2/前列腺素E2/EP-2/生长抑素受体-2轴发挥抗血管生成作用，从而下调细胞外信号调节激酶-缺氧诱导因子-1α-血管内皮生长因子α的磷酸化。结论：塞来昔布联合奥曲肽通过抑制肝内外血管生成，协同改善TAA诱导的肝硬变大鼠肝纤维化和门脉高压。其机制可能与p-ERK-HIF-1、α-血管内皮生长因子信号通路失活有关。
Abnormal angiogenesis is critical for portal hypertension in cirrhosis. Except for etiological treatment, no efficient medication or regime has been explored to treat the early stage of cirrhosis when angiogenesis is initiated or overwhelming. In this study, we explored an anti-angiogenesis effort through non-cytotoxic drugs octreotide and celecoxib to treat early stage of cirrhotic portal hypertension in an animal model. Peritoneal injection of thioacetamide (TAA) was employed to induce liver cirrhosis in rats. A combination treatment of celecoxib and octreotide was found to relieve liver fibrosis, portal venous pressure, micro-hepatic arterioportal fistulas, intrahepatic and splanchnic angiogenesis. Celecoxib and octreotide exerted their anti-angiogenesis effect via an axis of cyclooxygenase-2/prostaglandin E2/EP-2/somatostatin receptor-2, which consequently down-regulated phosphorylation of extracellular signal-regulated kinase (p-ERK)–hypoxia-inducible factor-1α (HIF-1α)–vascular endothelial growth factor (VEGF) integrated signaling pathways. In conclusions, combination of celecoxib and octreotide synergistically ameliorated liver fibrosis and portal hypertension of the cirrhotic rats induced by TAA via the inhibition of intrahepatic and extrahepatic angiogenesis. The potential mechanisms behind the regimen may due to the inactivation of p-ERK–HIF-1α–VEGF signaling pathway.
登录
查看更多内容
影响因子：
5.3
作者：
Mejias M;Garcia-Pras E;Tiani C;Bosch J;Fernandez M
通讯作者：
Fernandez M
影响因子：
13.5
作者：
Mejias, Marc;Garcia-Pras, Ester;Fernandez, Mercedes
通讯作者：
Fernandez, Mercedes
影响因子：
13.5
作者：
Pan, Ruo-Lang;Xiang, Li-Xin;Shao, Jian-Zhong
通讯作者：
Shao, Jian-Zhong
经导管动脉栓塞随后使用奥曲肽和塞来昔布可协同延长 VX2 同种异体肝移植兔的生存期。
影响因子：
3.5
作者：
Tong, Huan;Li, Xiao;Tang, Cheng Wei
通讯作者：
Tang, Cheng Wei
影响因子：
82.9
作者：
O'Brien AJ;Fullerton JN;Massey KA;Auld G;Sewell G;James S;Newson J;Karra E;Winstanley A;Alazawi W;Garcia-Martinez R;Cordoba J;Nicolaou A;Gilroy DW
通讯作者：
Gilroy DW