解偶联蛋白2与脂多糖诱导脓毒症大鼠心肌线粒体损伤的关系

发布时间：2018-01-02 12:22

本文关键词：解偶联蛋白2与脂多糖诱导脓毒症大鼠心肌线粒体损伤的关系　出处：《中国当代儿科杂志》2016年02期 　论文类型：期刊论文

【摘要】：目的探讨解偶联蛋白2(uncoupling protein 2,UCP2)与脂多糖诱导脓毒症大鼠心肌线粒体损伤的关系。方法通过腹腔注射脂多糖(LPS)建立脓毒症模型。将40只Sprague-Dawley(SD)雄性大鼠随机分为5组,每组8只:对照组(腹腔注射生理盐水)、脓毒症6 h组(LPS-6 h组)、脓毒症12 h组(LPS-12 h组)、脓毒症24 h组(LPS-24 h组)和脓毒症48 h组(LPS-48 h组)。在相应时间点留取大鼠血清和心脏组织,提取心肌线粒体,通过酶标仪检测肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)和活性氧(ROS)水平,流式细胞仪检测线粒体肿胀度和线粒体膜电位(MMP),采用蛋白质免疫印迹试验(Western blot)测定UCP2蛋白表达水平;电镜观察心肌组织线粒体形态学变化。结果与对照组比较,LPS各组血清CK、CK-MB水平、心肌组织ROS水平和线粒体肿胀度均明显升高(P0.05),峰值在LPS-24 h组;而LPS各组线粒体膜电位明显下降(P0.05),LPS-24 h组降至最低。Western blot检测发现LPS各组心肌组织UCP2的表达水平较对照组明显升高(P0.05),峰值在LPS-24 h组。电镜观察结果发现LPS大鼠心肌线粒体肿胀,线粒体膜部分破碎,有空泡形成,LPS-24 h组病变最严重。LPS大鼠心肌线粒体ROS水平、线粒体肿胀度与UCP2表达量呈正相关(分别r=0.796、0.893,P0.05);LPS大鼠心肌MMP与UCP2表达量呈负相关(r=-0.903,P0.05)。结论在脓毒症大鼠模型中,心肌和心肌线粒体都明显损伤,心肌组织UCP2的表达与线粒体损伤密切相关,推测UCP2可能在脓毒症心肌线粒体损伤中起重要作用。
[Abstract]:Objective to study uncoupling protein 2 of uncoupling protein 2. The relationship between UCP2) and myocardial mitochondria damage induced by lipopolysaccharide in sepsis rats. Methods the sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS). Forty Sprague-Dawley rats were selected. SD) male rats were randomly divided into 5 groups. There were 8 rats in each group: control group (intraperitoneal injection of normal saline, sepsis 6 h group, LPS-6 h group, sepsis 12 h group, LPS-12 h group). The rat serum and heart tissue were collected at the corresponding time points to extract myocardial mitochondria from sepsis group (n = 24) and sepsis group (n = 48 h). The levels of creatine kinase (CK), creatine kinase isozyme (CK-MBB) and reactive oxygen species (Ros) were detected by enzyme scale, and mitochondrial swelling degree and mitochondrial membrane potential (MMPs) were measured by flow cytometry (FCM). Western blotting assay was used to detect the expression of UCP2 protein. The changes of myocardial mitochondria morphology were observed by electron microscope. Results compared with the control group, the level of CKK-MB in serum of LPS group was higher than that of LPS group. The level of ROS and the degree of swelling of mitochondria in myocardial tissue were significantly increased (P 0.05), and the peak value was in the LPS-24 h group. However, the mitochondrial membrane potential in LPS group was significantly decreased (P 0.05). The expression of UCP2 in myocardium of LPS group was significantly higher than that of control group (P0.05). The peak value was in LPS-24 h group. The results of electron microscopic observation showed that myocardial mitochondria were swollen, mitochondrial membrane was partially broken and empty vesicles were formed in LPS rats. The level of myocardial mitochondrial ROS, mitochondrial swelling and UCP2 expression were positively correlated in the LPS-24 h group (r 0.796 卤0.893, respectively). P0.05; There was a negative correlation between the expression of MMP and UCP2 in the myocardium of LPS rats. Conclusion in the sepsis rat model, both myocardial and myocardial mitochondria were significantly damaged. The expression of UCP2 in myocardium is closely related to mitochondrial damage. It is suggested that UCP2 may play an important role in myocardial mitochondrial injury in sepsis.
【作者单位】：南方医科大学珠江医院儿科中心;东莞市厚街医院儿科;
【基金】：国家自然科学基金(81272070) 广东省科技计划项目(2014A020212725)
【分类号】：R459.4
【正文快照】： 脓毒症是机体对病原的免疫应答反应性疾病,其免疫学特征是宿主自身免疫损伤,进一步可发展为多器官功能障碍综合征(MODS)。心脏是脓毒症的靶器官之一,合并心功能障碍的脓毒症患者的病死率可高达70%[1-2]。研究发现活性氧(reactive oxygen species,ROS)生成过多、能量产生和代谢

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