Protective effects of pretreatment with rosiglitazone on the lungs against endotoxin-induced acute injury in rats
- VernacularTitle:罗格列酮预先给药对内毒素诱导大鼠急性肺损伤的保护作用
- Author:
Dong LIU
;
Bangxiong ZENG
;
Yuelan WANG
- Publication Type:Journal Article
- Keywords:
Thiazolidinediones;
Endotoxins;
Respiratory distress syndrome, adult
- From:
Chinese Journal of Anesthesiology
1995;0(10):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of rosiglitazone (ROSI), a potent agonist of peroxisome proliferator- activated receptor ?( PPAR?) on acute lung injury induced by endotoxin. Methods Thirty-six male Wistar rats weighing 200-250 g were randomly divided into 6 groups (n = 6 per group): group I control; group II ROSI; group III GW; group IV LPS; group V ROSI + LPS and group VI GW + ROSI + LPS. The animals were anesthetized with intraperitoneal 3 % pentobarbital 50 mg ? kg -1 . The jugular vein was cannulated for administration of fluid and drug. In group I , II and III normal saline (NS) 2 ml was given 30 min after IV 10% DMSO 2 ml? kg-1( I ), ROSI 0.3 mg?kg-1(dissolved in DMSO) or GW9662 (PPAR? antagonist) 0.3 mg?kg-1 ( III ) . In group IV , V and VI instead of NS LPS 6 mg? kg-1 was given 30 min after 10% DMSO ( IV ) or ROSI( V , VI). In group VI GW9662 0.3 mg?kg-1 was given IV 20 min before ROSI. The rats were sacrificed and the lungs were removed for microscopic examination and determination of wet/dry lung weight ( W/D) ratio and lung myeloperoxidase (MPO) activity and malondialdehyde (MDA) and NO content. The lung was also assessed for expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine ( NT) using Western blot analysis or immuno-histochemistry.Results LPS induced marked lung injury and significant increase in W/D ratio, MPO activity, MDA and NO content in the lung. All of these changes were significantly attenuated by pretreatment with ROSI. Pretreatment also significantly suppressed LPS-induced expression of iNOS protein and formation of nitrotyrosine in the lung. The specific PPAR? antagonist GW9662 counteracted the effects of ROSI. Conclusion Pretreatment with has protective effect against endotoxin-induced ALL The underlying mechanism is via the activation of PPAR?.
