EPO对脓毒症急性肺损伤大鼠血清中HMGB1、Bcl-2水平的影响

发布时间：2018-04-02 05:04

本文选题：促红细胞生成素　切入点：脓毒症　出处：《遵义医学院》2017年硕士论文

【摘要】：目的:通过建立大鼠脓毒症急性肺损伤模型,用EPO进行干预,观察肺组织病理改变及血清中HMGB1、Bcl-2水平变化,探讨EPO对脓毒症急性肺损伤是否具有保护作用。方法:体重为180~200g的健康SD雄性大鼠24只,随机分成:S组(对照组)、A组(ALI组)、E组(EPO治疗组)。建立脂多糖(LPS)二次打击大鼠ALI模型,即致大鼠双侧股骨骨折后6h,舌下静脉注射LPS 5mg/kg进行二次打击,完成模型制作。E组在LPS二次打击后立即静脉注射重组人促红细胞生成素(rh EPO)1000 IU/kg,A组和S组静脉注射等量的生理盐水,8h后获取肺组织和动脉血。血气分析检测Pa O2、Pa CO2、HCO3-、p H值;测定肺组织湿干比值(W/D);ELISA法检测了血清中HMGB1和Bcl-2水平;右肺上叶固定于4%多聚甲醛中,24h后行HE染色病理学检查;所得数据应用SPSS 17.0软件进行统计分析。结果:1)肺组织病理切片结果:S组大鼠肺泡结构完整,无炎性细胞浸润;A组大鼠肺泡结构完全破坏,肺泡内见炎性细胞浸润及不等量红细胞渗出;E组大鼠肺泡结构部分破坏,部分肺泡内见灶状泡沫细胞聚集及少量红细胞渗出,较A组相比两者都有不同程度的肺泡损伤及炎性病理改变,但A组肺泡结构破坏更加严重,炎性细胞及红细胞渗出更多。2)肺组织W/D值结果:肺组织W/D值在A组和E组分别为(6.05±0.64)、(5.33±0.57),与S组(4.48±0.25)相比均明显升高(P0.01),而A组又高于E组(P0.05)。3)血气分析结果:Pa O2在A组和E组分别为(58.4±1.3)mm Hg、(67±3.5)mm Hg,与S组相比(94.8±2.8)mm Hg均明显降低(P0.01),而A组又明显低于E组(P0.01);HCO3-、p H值在S组分别为(27.4±1.1)mmol/L、(7.38±0.41),A组分别为(22.4±3.1)mmol/L、(7.25±0.66),E组分别为(24.8±1.7)mmol/L、(7.32±0.42),A组HCO3-、p H值均低于S组(P0.01)和E组(P0.05),而E组HCO3-、p H值又均低于S组(P0.05);S组、A组和E组Pa CO2分别为(41.5±2.7)mm Hg、(40.2±5.8)mm Hg、(43.3±4.2)mm Hg,各组比较差异无统计学意义(P0.05)。4)血清中HMGB1、Bcl-2水平结果:血清中HMGB1水平在A组和E组分别为(1390.83±178.99)pg/ml、(1208.08±116.45)pg/ml,与S组(359.25±92.89)pg/ml相比均明显升高(P0.01),而A组又高于E组(P0.05);血清中Bcl-2水平在A组和E组分别为(1.71±0.55)ng/ml)、(2.53±0.38)ng/ml,与S组(4.31±0.86)ng/ml相比均明显降低(P0.01),而A组又低于E组(P0.05)。结论:EPO能减轻急性肺损伤大鼠肺组织炎症反应并下调血清中HMGB1水平和上调Bcl-2水平,对脓毒症急性肺损伤有保护作用。
[Abstract]:Objective: to establish acute lung injury model of sepsis in rats and to observe the pathological changes of lung tissue and the level of HMGB1 Bcl-2 in serum by EPO intervention. To investigate the protective effect of EPO on acute lung injury of sepsis. Methods: Twenty-four healthy male SD rats weighing 180 ~ 200g were randomly divided into two groups: control group (control group A) and Ali group (group E). Lipopolysaccharide (LPS) model of ALI was established in rats. LPS 5mg/kg was injected into sublingual vein 6 hours after bilateral femoral fracture in rats. The pulmonary tissue and arterial blood were obtained in group E after intravenous injection of recombinant human erythropoietin (rhEPO) -rh EPO)1000 IUP (group A) and group S (n = 8 h) immediately after the second strike of LPS. The blood gas analysis was performed to detect the value of Pa O _ 2Pa CO _ 2o _ 2H _ 2O _ 3-HCO3-HCO3-HCO3-HCO3-HCO3-HCO3-HCO3-H in group S and group A (n = 8), respectively. The levels of HMGB1 and Bcl-2 in serum were detected by WR / DX Elisa, and the pathological examination of HE staining was performed in the upper lobe of the right lung after 24 hours fixed in 4% paraformaldehyde. The data were analyzed by SPSS 17.0 software. Results the results of pathological section of lung tissue showed that the alveolar structure of rats in group S was intact, and the alveolar structure of group A was completely destroyed without inflammatory cell infiltration. Inflammatory cell infiltration and erythrocyte exudation were observed in the alveoli of rats in E group, the alveolar structure was partially destroyed, focal foam cells were accumulated in some alveoli and a few red blood cells exudated. Compared with group A, both of them had different degree of alveolar injury and inflammatory pathological changes, but the destruction of alveolar structure in group A was more serious. WR value of lung tissue in group A and E was 6.05 卤0.64, 5.33 卤0.57, which was significantly higher than that in group S (4.48 卤0.25), but in group A was higher than that in group E (P0.05n.3) blood gas analysis showed that WR / D in group A was higher than that in group A and E respectively. Compared with S group, 58.4 卤1.3)mm hgfg 67 卤3.5)mm Hg, 94.8 卤2.8)mm Hg significantly decreased P0.01U, and the HCO3-HCO3-tioph in group A was significantly lower than that in group E (27.4 卤1.1 mmol / L 7.38 卤0.41mol / L 7.38 卤0.41mol / L 7.38 卤0.41mmol / L), respectively, and the values of HCO3-Ph in group A were 24.8 卤1.7mmol-L / L 7.32 卤2.4mmol / L = 7.32 卤20.4mmol-1, respectively, which were lower than those in group S (P 0.01) and in group E (P < 0.01), respectively, but the values of CO3-pH in group E were 24.8 卤1.7mmol / L = 7.25 卤0.66mmol / L = 7.25 卤0.66kmol / L = 24.8 卤1.7mmol / L = 7.25 卤0.66mmol / L = 7.25 卤0.66mmol / L = 7.25 卤1.7mmol / L = 7.25 卤0.66g / h, respectively. It was also lower than that in group S (P 0.05): Pa CO2 of group A and group E were 41.5 卤2.7)mm 2.7)mm, 40.2 卤5.8)mm, 43.3 卤4.2)mm, respectively. There was no significant difference in serum HMGB1Bcl 2. Results: the level of serum HMGB1 in group A and E was 1390.83 卤178.99pg / ml, 1208.08 卤116.45pgml / ml, which was significantly higher than that in group S (359.25 卤92.89)pg/ml, P < 0.05). The serum HMGB1 level in group A and E was 1390.83 卤178.99p / ml / ml, 1208.08 卤116.45pgml / ml respectively, which was significantly higher than that in group S (359.25 卤92.89)pg/ml). The levels of serum Bcl-2 in group A and E were 1.71 卤0.55 ng / ml and 2.53 卤0.38 ng / ml, respectively, which were significantly lower than those in group S (4.31 卤0.86)ng/ml), but lower in group A than in group E (P 0.05). Modulating serum HMGB1 level and up-regulating Bcl-2 level, It has protective effect on acute lung injury of sepsis.
【学位授予单位】：遵义医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R459.7

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