Protective effect of endogenous PPARγ against acute gastric mucosal lesions associated with ischemia-reperfusion
Protective effect of endogenous PPARγ against acute gastric mucosal lesions associated with ischemia-reperfusion
复制标题
DOI：
10.1152/ajpgi.00523.2003
复制
发表时间：
2004-08-01
影响因子：
4.5
通讯作者：
Blumberg, RS
中科院分区：
文献类型：
--
作者：
Wada, K;Nakajima, A;Blumberg, RS
急性胃粘膜病变（AGML）是消化道出血的重要原因。在此，我们证明，过氧化物酶体增殖物激活受体-γ（PPARgamma），一个核受体家族的成员，作为一个内源性抗炎通路在AGML诱导的缺血再灌注（I/R）的小鼠模型的功能。在I/R诱导的AGML模型中检查了特异性PPARgamma配体如BRL-49653、吡格列酮或曲格列酮的治疗。还检查了PPARgamma缺陷型和野生型小鼠对胃I/R的反应。特异性PPARgamma配体以剂量依赖性方式对小鼠中与I/R相关的AGML形成表现出显著和快速的保护作用。相反，I/R诱导的AGML在PPARgamma缺陷型小鼠中比在野生型小鼠中观察到的更严重。给予PPARgamma配体可显著抑制胃I/R诱导的TNF-α、ICAM-1、诱导型一氧化氮合酶、细胞凋亡和硝基酪氨酸形成的上调。这些数据表明，与PPARgamma相关的内源性途径在胃I/R相关损伤的发病机制中起重要作用。
Acute gastric mucosal lesions (AGMLs) are an important cause of gastrointestinal bleeding. Herein, we demonstrate that peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of a nuclear receptor family, functions as an endogenous anti-inflammatory pathway in a murine model of AGML induced by ischemia-reperfusion (I/R). Treatment with specific PPARgamma ligands such as BRL-49653, pioglitazone, or troglitazone was examined in a model of AGML induced by I/R. PPARgamma-deficient and wild-type mice were also examined for their response to I/R in stomach. Specific PPARgamma ligands exhibited dramatic and rapid protection against AGML formation associated with I/R in mice in a dose-dependent manner. In contrast, the AGML induced by I/R in PPARgamma-deficient mice was more severe than that observed in wild-type mice. Administration of the PPARgamma ligand significantly inhibited the upregulation of TNF-alpha, ICAM-1, inducible nitric oxide synthase, apoptosis, and nitrotyrosine formation induced by I/R in the stomach. These data indicate that an endogenous pathway associated with PPARgamma plays an important role in the pathogenesis of I/R-associated injury in the stomach.