Terlipressin relieves intestinal and renal injuries induced by acute mesenteric ischemia via PI3K/Akt pathway.
Terlipressin relieves intestinal and renal injuries induced by acute mesenteric ischemia via PI3K/Akt pathway.
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特利加压素通过 PI3K/Akt 通路减轻急性肠系膜缺血所致肠肾损伤
DOI：
10.7150/ijms.46302
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发表时间：
2020
影响因子：
3.6
通讯作者：
Zhang XY
中科院分区：
文献类型：
--
作者：
Liu ZM;Lai HJ;Guan XD;Wen SH;Shen JT;Nie Y;Liu N;Zhang XY
背景：到目前为止，加压素对急性肠系膜缺血（MI）后器官损伤的作用仍知之甚少。目标：目的观察选择性血管加压素V1受体激动剂特利加压素与去甲肾上腺素对急性心肌梗死后肠、肾损伤的影响，并探讨其作用机制。方法：采用夹闭上级肠系膜动脉1 h的方法制备急性心肌梗死模型。松开后立即静脉内给予特利加压素或去甲肾上腺素2小时。同时，在体外，用脂多糖或脂多糖+特利加压素处理RAW264.7细胞。此外，Wortmannin用于确定磷脂酰肌醇3-激酶（PI 3 K）/蛋白激酶B（Akt）通路在特利加压素的潜在影响中的作用。结果如下：MI导致严重的低血压，引起显著的肠和肾损害，并导致高死亡率，特利加压素或去甲肾上腺素可显著改善这些情况。特利加压素可增加MI后平均动脉压，减少肠上皮细胞凋亡，抑制肠、肾组织M1巨噬细胞生成，抑制MI后炎性细胞因子的释放。此外，在培养的巨噬细胞中，特利加压素降低特定M1标记物的mRNA水平和由脂多糖激发引起的炎性细胞因子的释放。Wortmannin可降低特利加压素诱导的细胞和组织中PI 3 K和Akt的表达，并可消除特利加压素的上述保护作用。结论：特利加压素或去甲肾上腺素能有效改善急性心肌梗死后的脏器损害，降低死亡率。特利加压素通过PI 3 K/Akt途径升高血压并抑制肠上皮细胞凋亡和巨噬细胞M1极化。
Background: To date, the effect of vasopressin on organ damages after acute mesenteric ischemia (MI) remains poorly understood. Aims: To investigate the effect of terlipressin, a selective vasopressin V1 receptor agonist, versus norepinephrine on the intestinal and renal injuries after acute MI, and to explore the underlying mechanism of terlipressin. Methods: Acute MI model was produced by clamping the superior mesenteric artery for 1 hour. Immediately after unclamping, terlipressin or norepinephrine was intravenously administered for 2 hours. Meanwhile, in vitro, RAW264.7 cells were treated with lipopolysaccharide or lipopolysaccharide+terlipressin. In addition, wortmannin was used to determine the role of phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway in the potential impacts of terlipressin. Results: MI led to severe hypotension, caused notable intestinal and renal impairments and resulted in high mortality, which were markedly improved by terlipressin or norepinephrine. Terlipressin increased mean arterial pressure, decreased intestinal epithelial cell apoptosis, inhibited the generation of M1 macrophage in intestinal and renal tissues, and hindered the release of inflammatory cytokines after MI. Moreover, in cultured macrophages, terlipressin reduced the mRNA level of specific M1 markers and the release of inflammatory cytokines caused by lipopolysaccharide challenge. Wortmannin decreased the expression of PI3K and Akt induced by terlipressin in cells and in tissues, and abolished the above protective effects conferred by terlipressin. Conclusions: Terlipressin or norepinephrine could effectively improve organ damages and mortality after acute MI. Terlipressin elevates blood pressure and inhibits intestinal epithelial apoptosis and macrophage M1 polarization via the PI3K/Akt pathway.
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影响因子：
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作者：
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影响因子：
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作者：
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DOI：
10.1186/s13054-015-0825-9
发表时间：
2015-03-13
期刊：
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影响因子：
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作者：
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影响因子：
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