Protective effect of raloxifene on lipopolysaccharide and acid-induced acute lung injury in rats

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:a595165933
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Aim:To evaluate the protective effect of oral raloxifene on acute lung injury.Methods:Thirty adult,male Sprague-Dawley rats each weighing 180-210 g wereused and divided into 3 groups:the raloxifene-lipopolysaccharide (LPS)-HCl group(n=10),the LPS-raloxifene-HCl group (n=10),and the placebo group (n=10).Allthe rats were injected intraperitoneally (ip) with 5 mg/kg LPS,and raloxifene (30mg/kg) was orally administered 1 h before and 14 h after LPS injection into theraloxifene-LPS-HCl and the LPS-raloxifene-HCl groups,respectively;the placebogroup received nothing.Sixteen hours after LPS injection,all the animals wereanesthetized and the femoral artery was cannulated.All the rats received a directintratracheal (IT) injection of HCl(pH 1.2;0.5 mL/kg).The mean arterial pressure(MAP) and blood gas concentrations were measured.Fifteen rats (5 in eachgroup,respectively) underwent a micro positron emission tomography (microPET)scan of the thorax 4 h after HCl instillation.The wet/dry (W/D) weight ratiodetermination and histopathological examination were also performed.Results:The rats in the LPS-raloxifene-HCl group had a lower [~(18)F]fluorodeoxyglucoseuptake compared with the rats in the placebo group (4.67±1.33 vs 9.01±1.58,respectively,P<0.01).The rats in the LPS-raloxifene-HCl group also had a lowerhistological lung injury score (8.20±1.23 vs 12.6±0.97,respectively,P<0.01) andW/D weight ratio (5.335±0.198 vs 5.886±0.257,respectively,P<0.01) compared tothe placebo group.The rats in this group also showed better pulmonary gasexchange and more stable mean arterial pressure (MAP) compared to the placebogroup.Conclusion:Raloxifene provides a significant protective effect on acutelung injury in rats induced first by LPS ip injection and then by HCl IT instillation. Aim: To evaluate the protective effect of oral raloxifene on acute lung injury. Methods: Thirty adult, male Sprague-Dawley rats each weighing 180-210 g were used and divided into 3 groups: the raloxifene-lipopolysaccharide (LPS) (N = 10), and the placebo group (n = 10). All rats were injected intraperitoneally (ip) with 5 mg / kg LPS, and raloxifene (30 mg / kg) Orally administered 1 h before and 14 h after LPS injection into theraloxifene-LPS-HCl and the LPS-raloxifene-HCl groups, respectively; the placebogroup received nothing. Sixteen hours after LPS injection, all the animals wereanesthetized and the femoral artery was cannulated. All the rats received a direct inratracheal (IT) injection of HCl (pH 1.2; 0.5 mL / kg). The mean arterial pressure (MAP) and blood gas concentrations were measured. tomography (microPET) scan of the thorax 4 h after HCl instillation. The wet / dry (W / D) weigh Results: The rats in the LPS-raloxifene-HCl group had a lower [~ (18) F] fluorodeoxyglucose uptake compared with the rats in the placebo group (4.67 ± 1.33 vs 9.01 ± 1.58, respectively) , P <0.01). The rats in the LPS-raloxifene-HCl group also had a lowerhistological lung injury score (8.20 ± 1.23 vs 12.6 ± 0.97, respectively, P <0.01) and W / D weight ratio (5.335 ± 0.198 vs 5.886 ± 0.257, respectively, P <0.01) compared to placebo group. The rats in this group also showed better pulmonary gasexchange and more stable mean arterial pressure (MAP) compared to the placebogroup. Confluence: Raloxifene provides a significant protective effect on acute injury in rats induced first by LPS ip injection and then by HCl IT instillation.
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