Department of Experimental Medicine, Excellence Centre for Cardiovascular Diseases, Second University of Naples, Naples, Italy.
Shock. 2009 Dec;32(6):638-44. doi: 10.1097/SHK.0b013e3181a5a377.
Thiazolidinediones are ligands that bind to and activate the nuclear peroxisome proliferator-activated receptor gamma. They are widely used as insulin sensitizers for the treatment of type 2 diabetes. Several studies have implicated the peroxisome proliferator-activated receptor gamma agonists rosiglitazone and pioglitazone in inflammatory events. To assess the anti-inflammatory properties of rosiglitazone, we investigated its effects on the molecular and cellular inflammatory response induced by a carotid injury in the rat. Male Wistar rats were randomized into a rosiglitazone-treated group (10 mg kg(-1) day(-1)) and a control group (0.9% w/v NaCl). The drug or vehicle was administered by gavage for 7 days before carotid injury and for up to 21 days after injury. The inflammatory markers p38 mitogen-activated protein kinase, cyclooxygenase 2, nuclear factor-kappaB, and heat shock protein 47 and the influx and activity of cells in response to injury were measured. Rosiglitazone treatment significantly reduced the expression of the inflammatory markers compared with control group. p38 mitogen-activated protein kinase and nuclear factor-kappaB started to decrease a few hours after injury, whereas cyclooxygenase 2 and heat shock protein 47 expression decreased 7 and 14 days, respectively, after injury. Rosiglitazone also reduced neointima formation and inflammatory cell infiltration. In conclusion, rosiglitazone negatively regulated the inflammatory events involved in tissue repair at molecular and cellular levels. These results suggest that rosiglitazone plays a protective role in inflammatory vascular diseases.
噻唑烷二酮类药物是与核过氧化物酶体增殖物激活受体 γ 结合并激活该受体的配体。它们被广泛用作治疗 2 型糖尿病的胰岛素增敏剂。有几项研究表明，过氧化物酶体增殖物激活受体 γ 激动剂罗格列酮和吡格列酮与炎症事件有关。为了评估罗格列酮的抗炎特性，我们研究了它对大鼠颈动脉损伤诱导的分子和细胞炎症反应的影响。雄性 Wistar 大鼠随机分为罗格列酮治疗组（10mg/kg/d）和对照组（0.9%w/v NaCl）。在颈动脉损伤前 7 天和损伤后 21 天内，通过灌胃给予药物或载体。测量炎症标志物 p38 丝裂原活化蛋白激酶、环氧化酶 2、核因子-κB、热休克蛋白 47 以及对损伤的细胞流入和活性。与对照组相比，罗格列酮治疗显著降低了炎症标志物的表达。p38 丝裂原活化蛋白激酶和核因子-κB 在损伤后数小时开始下降，而环氧化酶 2 和热休克蛋白 47 的表达分别在损伤后 7 天和 14 天下降。罗格列酮还减少了新生内膜形成和炎症细胞浸润。总之，罗格列酮在分子和细胞水平上负调控参与组织修复的炎症事件。这些结果表明，罗格列酮在炎症性血管疾病中发挥保护作用。
