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大鼠脂肪栓塞综合征时脂氧素A4及其受体的变化

Changes in expressions of lipoxin A4 and its receptor in rats with fat embolism syndrome

摘要目的 探讨不同时间脂肪栓塞综合征(FES)动物模型中内源性脂氧素A4(LXA4)及LXA4受体(ALX)的变化. 方法 健康成年雄性SD大鼠尾静脉注射同种异体肾周脂肪0.706 ml/kg,建立大鼠FES模型.(1)60只SD大鼠按随机数表法分为FES l h组、FES 6 h组、FES 12 h组、FES 24 h组和对照组(注射等量的等渗盐水),每组12只,镜下观察肺组织表现,测定支气管肺泡灌洗液(BALF)中总蛋白和LXA4浓度变化,肺组织湿/干重(W/D)比值、髓过氧化物酶(MPO)活性和ALX mRNA的表达水平.(2)40只SD大鼠按随机数表法分为对照组(注射等量的等渗盐水)、FES 24 h组、ALX激动剂(BML-111)+FES 24 h组和ALX抑制剂(Boc-2)+FES24 h组,每组10只,镜下观察肺组织表现,检测肺组织MPO mRNA的表达水平. 结果 (1)与对照组比较,FES各组肺组织损伤严重.FES 12 h组BALF中总蛋白浓度为(71.12±11.05) μg/ml,较对照组的(29.82±0.64)μg/ml明显升高(P<0.05).FES24h组BALF中LXA4浓度为(2.72±0.24) ng/ml,较对照组的(0.69±0.05) ng/ml明显升高(P<0.05).肺组织W/D值FES6h组和FES 12 h组分别为9.13±0.83和9.60±0.86,均较对照组的3.09±0.10明显升高(P<0.05).FES 6 h组和12h组肺组织MPO的活性分别为(0.74±0.07) U/g和(0.53±0.08)U/g,均较对照组的(0.19±0.03) U/g明显增高(P<0.05).FES 24 h组ALX mRNA的表达为3.99±1.09,较对照组1.00±0.21明显升高(P<0.05).(2)BML-111 +FES24 h组MPO mRNA表达为0.69±0.08,较FES 24 h组的1.52±0.07明显降低,而较Boc-2+FES 24 h组的2.05±0.14明显升高(P<0.05). 结论 LXA4主要参与了FES大鼠肺部炎症消退过程,至少部分是通过与ALX结合发挥作用的.

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abstractsObjective To investigate the change in expressions of lipoxin A4 (LXA4) and lipoxin A4 receptor (ALX) in rats with fat embolism syndrome(FES).Metbods Sixty healthy male SD rats were assigned to control group and FES group which was subgrouped at l,6,12 and 24 h according to the random number table,with 12 rats each.Allogeneic perinephric fat (0.706 ml/kg) was injected to rat caudal veins in FES group.Instead isotonic saline in an equal volume was given to rats in control group.Lung samples were harvested from each group to detect pathological morphology,concentration of total protein and LXA4 in bronchoalveolar lavage fluid (BALF),lung weight to dry ratio (W/D),and activity of myeloperoxidase (MPO) and ALX mRNA.Additional 40 SD rats were divided into control group,FES 24-hour group,BML-1 11 + FES 24-hour group,and Boc-2 + FES 24-hour group according to the random number table,with 10 rats each.Pathology of lung tissue was observed using microscopy and expression of lung MPO mRNA was detected.Results Lung tissues in FES group were seriously injured compared with control group.Total protein concentration in BALF was (71.12 ± 11.05) μg/ml in FES 12-hour group,significantly increased compared to (29.82 ± 0.64) μg/ml in control group (P < 0.05).LXA4 concentration in BALF was (2.72 ± 0.24) ng/ml in FES 24-hour group,significantly higher than (0.69 ±0.05)ng/ml in control group (P < 0.05).Lung W/D value was 9.13 ±0.83 and 9.60 ±0.86 respectively in FES 6-hour and 12-hour groups,higher than 3.09 ±0.10 in control group (P <0.05).Activity of MPO in lung tissue was (0.74± 0.07)U/g and (0.53 ±0.08)U/g respectively in FES 6-hour and 12-hour groups,significantly higher than (0.19 ± 0.03) U/g in control group (P < 0.05).Expression of ALX mRNA was 3.99 ± 1.09 in FES 24-hour group,significantly higher than 1.00 ±0.21 in control group (P <0.05).Expression of MPO mRNA was lower in BML-111 + FES 24-hour group (0.69-0.08) and was higher in Boc-2 + FES 24-hour group (2.05-0.14),when compared to 1.52 ±-0.07 in FES 24-hour group (P<0.05).Conclusion LXA4 mainly involves in the resolution of inflammation in FES rats,which may be achieved at least in part by binding to ALX.

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栏目名称 基础研究
DOI 10.3760/cma.j.issn.1001-8050.2016.04.013
发布时间 2016-05-23
基金项目
国家自然科学基金(81272147) National Natural Science Foundation of China
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