脓毒症大鼠心肌损伤标志物和炎症因子变化及血必净注射液干预作用

发布时间：2018-02-28 06:29

本文关键词： 脓毒症心肌损伤肌钙蛋白T心脏型脂肪酸结合蛋白肿瘤坏死因子血必净注射液　出处：《天津医科大学》2012年硕士论文　论文类型：学位论文

【摘要】：目的：通过动物实验观察盲肠结扎穿孔术(cecal ligation and puncture,CLP)后大鼠心肌损伤标志物心脏型-脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)、肌钙蛋白T(TroponinT,TnT)、肌酸激酶同工酶(Creatine kinase isoenzyme, CK-MB)和脑钠肽(Brain natriuretic peptide, BNP)、肿瘤坏死因子(tumor necrosis factor,TNF)-α表达的变化及血必净注射液对其干预作用。探讨脓毒症大鼠心肌抑制的可能机制和血必净注射液对脓毒症大鼠心肌抑制的改善。方法：1.将78只清洁级雄性wistar大鼠随机分为4组：正常对照组、假手术组、CLP组和血必净组。2.正常对照组于麻醉后经腹主动脉无菌取血,假手术组、CLP组和血必净组于手术后6、24、48和72h经腹主动脉无菌取血,离心后留取血清。3.应用酶联免疫吸附剂方法(Enzyme-Linked Immuno sorbent Assay,ELISA)检测大鼠血清TnT、CK-MB、H-FABP、BNP和TNF-α浓度。4.将大鼠处死后迅速取出心脏,切取心室肌,HE染色,观察心肌组织病理改变。5.采用spss17.0统计软件包进行数据处理。所有数据均采用均数±标准差表示。多个样本均数比较采用单因素方差分析One-way ANOVA, P0.05差异有统计学意义。两变量关联性采用线性相关分析,相关程度应用Pearson积差相关系数表示。结果：1.CLP术后大鼠出现一般状态改变,血必净组大鼠较CLP组症状减轻。血必净组大鼠死亡率较CLP组降低,四个时间点的死亡率两两比较差异无统计学意义(P0.05)。2.光镜下可见CLP术后大鼠心肌组织形态发生改变,CLP组与对照组和假手术组比较,心肌细胞排列紊乱,细胞肿胀,空泡变性,心肌细胞皱缩,炎症细胞浸润,心肌纤维断裂,核膜破裂,细胞核肿胀,随时间延长变化越明显；血必净组大鼠心肌细胞上述改变较CLP组明显减轻。3.CLP组6h血清TnT、 H-FABP、CK-MB浓度较对照组、假手术组明显升高(P0.01),随时间延长,TnT、H-FABP、CK-MB浓度有所降低,血必净能够显著降低血清TnT、H-FABP、 CK-MB浓度,各时间点显著低于CLP组(P0.01)。CLP组6h血清BNP浓度较对照组、假手术组显著升高(P0.01),随时间延长,BNP持续升高,血必净组BNP浓度各时间点较CLP组明显降低(P0.01),但各时间点仍高于对照组和假手术组(P0.05)。4.CLP组6h血清TNF-α浓度较对照组、假手术组明显升高(P0.01),随时间延长,血清TNF-α浓度持续升高,血必净组TNF-α浓度在各时间点较CLP组降低(P0.05),6h、24h能显著降低TNF-α浓度,48h和72h时也可降低TNF-α浓度,但仍高于对照组和假手术组。5.相关分析显示,脓毒症大鼠血清TNF-α与TnT、CK-MB、BNP、H-FABP浓度的变化值呈正相关。结论：1.盲肠结扎穿孔法能制备稳定、可靠的脓毒症大鼠模型。2.脓毒症大鼠早期即出现明显心肌损伤和心功能障碍,表现为心脏组织病理形态学异常,血清TnT、CK-MB、HFABP和BNP升高。3.TNF-a在脓毒症大鼠心肌损伤的发生发展中具有一定作用。4.血必净注射液可能通过降低炎症因子水平而发挥心肌保护作用。
[Abstract]:Objective: to observe the myocardial injury markers heart-type fatty acid-binding protein H-FABPN, troponin Troponin TnTN, creatine kinase isoenzyme creatine kinase isoenzyme (CK-MBB) and brain natriuretic peptide (brain natriuretic peptide) in rats after cecal ligation and puncture after cecal ligation and perforation. The effect of Xuebijing injection on myocardial inhibition in septic rats and the improvement of Xue Bijing injection on myocardial inhibition in septic rats were investigated. Methods Seventy-eight clean male wistar rats were randomly divided into 4 groups: normal control group, sham operation group and Xuebijing group. In sham operation group and Xuebijing group, aseptic blood was collected from abdominal aorta at 6h 24 h and 72 h after operation, and serum .3.Enzyme-Linked Immuno sorbent assay was used to detect the concentration of TnTM-CK-MBH-FABPBNP and TNF- 伪 in serum of rats. The ventricular muscle was stained with HE. Observation of myocardial histopathology. 5. Spss17.0 statistical software package was used to process the data. All the data were expressed as mean 卤standard deviation. Single factor ANOVA was used to compare the mean of multiple samples. There was significant difference between them (P0.05). The correlation of two variables was analyzed by linear correlation analysis, The correlation degree is expressed by Pearson product difference correlation coefficient. Results 1. There were general changes in the state of rats after CLP. The symptoms of Xuebijing group were lighter than those of CLP group, and the mortality rate of Xuebijing group was lower than that of CLP group. There was no significant difference in mortality at four time points (P 0.05). Under light microscope, myocardial histomorphology changes were observed in CLP group. Compared with control group and sham operation group, myocardial cells were disordered, cell swelling and vacuolar degeneration were observed in CLP group. The changes of myocardial cell shrinkage, inflammatory cell infiltration, myocardial fiber rupture, nuclear membrane rupture and nuclear swelling were more obvious with the prolongation of time. The above changes of cardiac myocytes in Xuebijing group were significantly reduced than those in CLP group. 3. Compared with the control group, the serum TnTnTnH-FABPnCK-MB concentration in the CLP group was significantly lower than that in the control group, and the level of CK-MB in the sham-operated group was significantly higher than that in the control group, and the CK-MB concentration of TnTH-FABPnP was decreased with the extension of time, and Xuebijing could significantly reduce the CK-MB concentration in serum TnTH-FABPnPn. At each time point, the serum BNP concentration in CLP group was significantly lower than that in control group at 6 h, and that in sham operation group was significantly higher than that in control group. The concentration of BNP in Xuebijing group was significantly lower than that in CLP group at each time point, but at each time point it was still higher than that in control group and sham-operation group at 6 h, and the serum TNF- 伪 level in sham operation group was significantly higher than that in control group. The concentration of TNF- 伪 in Xuebijing group was significantly lower than that in CLP group at each time point at 6 h and 24 h, but it was still higher than that in control group and sham operation group at 48 h and 72 h. The correlation analysis showed that the concentration of TNF- 伪 in Xuebijing group was higher than that in control group and sham operation group. There was a positive correlation between serum TNF- 伪 and the concentration of BNPH-FABP in the serum of sepsis rats. Conclusion 1. The method of cecal ligation and perforation can make a stable and reliable sepsis rat model .2.There are obvious myocardial damage and cardiac dysfunction in sepsis rats at the early stage, which is characterized by abnormal pathomorphology of heart tissue. HFABP and BNP increased in serum TNF-a may play a role in the occurrence and development of myocardial injury in septic rats. Xuebijing injection may play a role in myocardial protection by lowering the level of inflammatory factors.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R459.7

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