乌司他丁对宫内窘迫致胎鼠急性肺损伤的影响
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重庆市卫生局科研资助项目(2013?2?138)


Influence of ulinastatin on acute lung injury in fetal rat induced by fetal distress
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    摘要:

    目的:探讨乌司他丁对宫内窘迫致胎鼠急性肺损伤的影响,以期为临床上治疗宫内窘迫致新生儿呼吸窘迫综合征提供新的治疗方案。方法:健康孕20 d的SD大鼠16只,采用随机数字表法分为4组,每只孕大鼠取5只活胎鼠(n=20),分为对照组(C组)、乌司他丁对照组(S组)、宫内窘迫组(A组)、乌司他丁治疗组(U组)。C组与S组为假手术组,A组和U组建立宫内窘迫模型,S组和U组在手术前30 min经孕大鼠股静脉注射乌司他丁50 000 U/kg。取胎鼠收集外周血行血气分析,测定胎鼠肺湿/干质量比值(W/D),HE染色观察胎鼠肺组织病理改变;Western blot方法测定肺组织NF-κB p65蛋白表达水平;ELISA方法测定肿瘤坏死因子(tumor necrosis factor,TNF)-α及白细胞介素(interleukin,IL)-6含量。结果:C组与S组胎鼠血气分析、W/D值、肺组织形态、NF-κB p65蛋白表达水平、TNF-α及IL-6含量差异均无统计学意义(P > 0.05);与C组相比,A组CO2分压(PCO2)、乳酸(Lac)含量明显增高,pH、氧分压(PO2)降低,W/D值增大,NF-κB p65蛋白表达水平增高,TNF-α及IL-6含量增多(P<0.05),肺组织明显水肿充血;与A组相比,U组PCO2、Lac含量明显降低,pH、PO2增高,W/D值、NF-κB p65蛋白表达水平、TNF-α及IL-6含量降低(P<0.05),肺组织水肿充血情况明显好转。结论:乌司他丁可降低胎鼠肺组织中NF-κB的细胞信号转导,减少TNF-α和IL-6等炎症因子的合成,抑制炎症反应,提高胎鼠血氧分压,减轻宫内窘迫造成的胎鼠急性肺损伤。

    Abstract:

    Objective:The goal of this study is to explore the effects of ulinastatin on acute lung injury in fetal rat induced by fetal distress,and provide support for developing a new treatment of respiratory distress syndrome. Methods:A total of 16 SD pregnant rats were randomly divided into four groups:the control group(group C),the ulinastatin control group(group S),the fetal distress group(group A),and the ulinastatin treatment group(group U). Group C and group S were sham operation groups. Fetal rat intrauterine distress model was set up in both group A and group U. Thirty minutes before the operations,the pregnant rats in group S and group U received injection of ulinastatin 50 000 U/kg through femoral vein. Five living fetal rats were removed in each pregnant rat. The blood gas analysis and the lung wet / dry weight ratio(W/D)of fetal rats were determined. The pathological changes in the lung tissue of fetal rats were observed by H&E staining,and the protein expression of NF-κB p65 were measured by Western blot. Furthermore,the levels of TNF-α and IL-6 in the fetal lung were measured by ELISA. Results:All the results in group S had no significant difference with group C(P >0.05). The pH value and partial pressure of oxygen were significantly lower in group A than group C,and those in group U were obviously higher than group A(P<0.05). The partial pressure of carbon dioxide,lactic acid content,the lung W/D,and the protein expression of NF-κB p65,the levels of TNF-α and IL-6 of fetal rats were all significantly increased in group A than group C(P<0.05),and those in group U were obviously lower than those in group A(P<0.05). The congestion and edema of the lung tissue in group U were obviously alleviated than that of group A. Conclusion:Ulinastatin can alleviate the degree of acute lung injury in fetal rat induced by fetal distress by decreasing the protein expression of NF-κB p65,the levels of TNF-α and IL-6,inhibiting the inflammatory response and increasing the partial pressure of oxygen.

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戴 珩,蔡 孟,李有长.乌司他丁对宫内窘迫致胎鼠急性肺损伤的影响[J].南京医科大学学报(自然科学版),2018,(11):1512-1516

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  • 收稿日期:2017-09-24
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  • 在线发布日期: 2018-12-03
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