乌司他丁对脓毒症大鼠血管内皮细胞损伤保护作用及机制研究

发布时间：2018-02-03 16:52

本文关键词： 乌司他丁脓毒症血管内皮细胞炎症凋亡　出处：《中国临床药理学杂志》2016年08期 　论文类型：期刊论文

【摘要】：目的研究乌司他丁对脓毒症大鼠血管内皮细胞(VEC)损伤保护作用及机制研究。方法 40只SD雄性大鼠按体重随机分为4组:假手术组,模型组及2个剂量实验组(乌司他丁,10×10~4,20×10~4U·kg~(-1)),其中模型组及实验组应用盲肠结扎穿孔(CLP)构建脓毒症大鼠模型。免疫酶联吸附法(ELISA)检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)及IL-6含量;试剂盒法检测血清一氧化氮(NO)及诱导型一氧化氮合酶(iNOS)含量;流式细胞术检测VEC凋亡情况;分光光度法检测血清中含半胱氨酸的天冬氨酸水解酶3(Caspase 3)活性;免疫印迹法分析各组B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)含量变化及核因子-κB(NF-κB)信号通路的激活状况。结果与假手术组比较,模型组中TNF-α、I L-1β、IL-6、NO、iNOS含量与VEC凋亡率及Caspase 3的活性均显著提高,Bax表达量明显上升,而Bcl-2表达量明显下降,NF-κB p65及IκBα磷酸化水平明显提高(均P0.01);与模型组比较,2个剂量实验组皆能显著抑制上述指标的变化(P0.05)。其中Caspase 3活性比值为(1.00±0.21,3.70±0.25,1.83±0.14,1.53±0.13)。结论乌司他丁对脓毒症大鼠VEC损伤具有保护作用,这可能与NF-κB信号通路有关。
[Abstract]:Objective to study the protective effect and mechanism of ulinastatin on vascular endothelial cell (VEC) injury in septic rats. Methods Forty SD male rats were randomly divided into 4 groups according to their body weight: sham operation group. The model group and two experimental groups (ulinastatin 10 脳 10 ~ (4) U 路kg ~ (-1)) were used as the experimental group (20 脳 10 ~ (4) U 路kg ~ (-1)). The model group and experimental group were used to establish sepsis rat model by cecal ligation and perforation. Serum tumor necrosis factor- 伪 (TNF- 伪) was detected by Elisa. Interleukin-1 尾 (IL-1 尾) and IL-6 content; Serum nitric oxide (no) and inducible nitric oxide synthase (iNOS) were detected by Kit method. Apoptosis of VEC was detected by flow cytometry. The activity of aspartate hydrolase 3 (caspase 3) containing cysteine in serum was detected by spectrophotometry. Immunoblotting assay was used to analyze B lymphocytoma Bcl-2 in each group. The changes of Bcl-2 related X protein (Bcl-2) content and the activation of NF-魏 B in NF- 魏 B signaling pathway. Results compared with sham operation group, TNF- 伪 -TNF- 伪 -1-1- 尾 was found in model group. The content of iNOS, apoptosis rate of VEC and the activity of Caspase 3 increased significantly, while the expression of Bcl-2 decreased significantly. The phosphorylation levels of NF- 魏 B p65 and I 魏 B 伪 were significantly increased (all P 0.01). Compared with the model group, the two dose groups could significantly inhibit the change of the above indexes (P 0.05), and the ratio of Caspase 3 activity was 1. 00 卤0. 21. Conclusion Ulinastatin has protective effect on VEC damage in septic rats. This may be related to NF- 魏 B signaling pathway.
【作者单位】：云南省第一人民医院重症医学科;云南省第一人民医院皮肤科;
【基金】：云南省科技厅昆明医科大学联合基金资助项目(2014FZ066)
【分类号】：R965
【正文快照】： 脓毒症是创伤、烧伤、休克、感染、外科手术后常见并发症,严重者可进一步发展为脓毒症休克和多器官功能障碍综合征,已成为临床危重病患者重要死亡原因之一[1-2]。乌司他丁是一种临床上用于抗急性组织损伤、减弱炎症损害的尿胰蛋白酶抑制剂,乌司他丁可改善脓毒症患者免疫及心脏

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