Liu D, Zeng B X, Zhang S H, Yao S L
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Inflamm Res. 2005 Nov;54(11):464-70. doi: 10.1007/s00011-005-1379-0.
The effect of rosiglitazone, a potent peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist, on pulmonary inflammation in endotoxemia was investigated.
Male Wistar rats were given either lipopolysaccharide (LPS, 6 mg/kg i.v.) or saline, pretreated with rosiglitazone (0.3 mg/kg i.v.) or its vehicle (dimethyl sulphoxide) 30 min before LPS. The selective PPAR-gamma antagonist GW9662 (0.3 mg/kg i.v.) was given 20 min before rosiglitazone. Wet/dry weight (W/D) ratio, myeloperoxidase (MPO) activity, malondialdehyde (MDA) as well as TNF-alpha and CINC-1 concentrations were measured in lung tissues 4 h after LPS injection. Expression of ICAM-1, NF-kappaB p65 and PPAR-gamma were also determined by immunohistochemistry or Western blot analysis.
Rosiglitazone pretreatment significantly attenuated the increases in W/D ratio, MPO activity and MDA levels, and reduced pulmonary overproduction of TNF-alpha and CINC-1 as well as expression of ICAM-1 following endotoxemia. Rosiglitazone also inhibited the nuclear localization of NF-kappaB and up-regulated the expression of PPAR-gamma protein. The specific PPAR-gamma antagonist GW9662 abolished the effect of rosiglitazone.
These findings suggest that PPAR-gamma agonists might be used as therapeutic agents in the therapy of inflammatory lung injury related to endotoxemia.
研究强效过氧化物酶体增殖物激活受体γ（PPAR-γ）激动剂罗格列酮对内毒素血症时肺部炎症的影响。
雄性Wistar大鼠静脉注射脂多糖（LPS，6mg/kg）或生理盐水，在注射LPS前30分钟用罗格列酮（0.3mg/kg静脉注射）或其溶媒（二甲基亚砜）进行预处理。在注射罗格列酮前20分钟给予选择性PPAR-γ拮抗剂GW9662（0.3mg/kg静脉注射）。在注射LPS后4小时测定肺组织的湿/干重（W/D）比值、髓过氧化物酶（MPO）活性、丙二醛（MDA）以及肿瘤坏死因子-α（TNF-α）和趋化因子-1（CINC-1）浓度。还通过免疫组织化学或蛋白质印迹分析测定细胞间黏附分子-1（ICAM-1）、核因子-κB p65（NF-κB p65）和PPAR-γ的表达。
罗格列酮预处理显著减轻了内毒素血症后W/D比值、MPO活性和MDA水平的升高，减少了肺部TNF-α和CINC-1的过量产生以及ICAM-1的表达。罗格列酮还抑制了NF-κB的核定位并上调了PPAR-γ蛋白的表达。特异性PPAR-γ拮抗剂GW9662消除了罗格列酮的作用。
这些发现表明PPAR-γ激动剂可能用作治疗与内毒素血症相关的炎症性肺损伤的治疗药物。
