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膿毒癥大鼠心肌損傷標志物和炎癥因子變化及血必凈注射液干預作用

發(fā)布時間:2018-02-28 06:29

  本文關鍵詞: 膿毒癥 心肌損傷 肌鈣蛋白T心臟型脂肪酸結合蛋白 腫瘤壞死因子 血必凈注射液 出處:《天津醫(yī)科大學》2012年碩士論文 論文類型:學位論文


【摘要】:目的:通過動物實驗觀察盲腸結扎穿孔術(cecal ligation and puncture,CLP)后大鼠心肌損傷標志物心臟型-脂肪酸結合蛋白(heart-type fatty acid-binding protein,H-FABP)、肌鈣蛋白T(TroponinT,TnT)、肌酸激酶同工酶(Creatine kinase isoenzyme, CK-MB)和腦鈉肽(Brain natriuretic peptide, BNP)、腫瘤壞死因子(tumor necrosis factor,TNF)-α表達的變化及血必凈注射液對其干預作用。探討膿毒癥大鼠心肌抑制的可能機制和血必凈注射液對膿毒癥大鼠心肌抑制的改善。 方法:1.將78只清潔級雄性wistar大鼠隨機分為4組:正常對照組、假手術組、CLP組和血必凈組。2.正常對照組于麻醉后經(jīng)腹主動脈無菌取血,假手術組、CLP組和血必凈組于手術后6、24、48和72h經(jīng)腹主動脈無菌取血,離心后留取血清。3.應用酶聯(lián)免疫吸附劑方法(Enzyme-Linked Immuno sorbent Assay,ELISA)檢測大鼠血清TnT、CK-MB、H-FABP、BNP和TNF-α濃度。4.將大鼠處死后迅速取出心臟,切取心室肌,HE染色,觀察心肌組織病理改變。5.采用spss17.0統(tǒng)計軟件包進行數(shù)據(jù)處理。所有數(shù)據(jù)均采用均數(shù)±標準差表示。多個樣本均數(shù)比較采用單因素方差分析One-way ANOVA, P0.05差異有統(tǒng)計學意義。兩變量關聯(lián)性采用線性相關分析,相關程度應用Pearson積差相關系數(shù)表示。 結果:1.CLP術后大鼠出現(xiàn)一般狀態(tài)改變,血必凈組大鼠較CLP組癥狀減輕。血必凈組大鼠死亡率較CLP組降低,四個時間點的死亡率兩兩比較差異無統(tǒng)計學意義(P0.05)。2.光鏡下可見CLP術后大鼠心肌組織形態(tài)發(fā)生改變,CLP組與對照組和假手術組比較,心肌細胞排列紊亂,細胞腫脹,空泡變性,心肌細胞皺縮,炎癥細胞浸潤,心肌纖維斷裂,核膜破裂,細胞核腫脹,隨時間延長變化越明顯;血必凈組大鼠心肌細胞上述改變較CLP組明顯減輕。3.CLP組6h血清TnT、 H-FABP、CK-MB濃度較對照組、假手術組明顯升高(P0.01),隨時間延長,TnT、H-FABP、CK-MB濃度有所降低,血必凈能夠顯著降低血清TnT、H-FABP、 CK-MB濃度,各時間點顯著低于CLP組(P0.01)。CLP組6h血清BNP濃度較對照組、假手術組顯著升高(P0.01),隨時間延長,BNP持續(xù)升高,血必凈組BNP濃度各時間點較CLP組明顯降低(P0.01),但各時間點仍高于對照組和假手術組(P0.05)。4.CLP組6h血清TNF-α濃度較對照組、假手術組明顯升高(P0.01),隨時間延長,血清TNF-α濃度持續(xù)升高,血必凈組TNF-α濃度在各時間點較CLP組降低(P0.05),6h、24h能顯著降低TNF-α濃度,48h和72h時也可降低TNF-α濃度,但仍高于對照組和假手術組。5.相關分析顯示,膿毒癥大鼠血清TNF-α與TnT、CK-MB、BNP、H-FABP濃度的變化值呈正相關。 結論:1.盲腸結扎穿孔法能制備穩(wěn)定、可靠的膿毒癥大鼠模型。2.膿毒癥大鼠早期即出現(xiàn)明顯心肌損傷和心功能障礙,表現(xiàn)為心臟組織病理形態(tài)學異常,血清TnT、CK-MB、HFABP和BNP升高。3.TNF-a在膿毒癥大鼠心肌損傷的發(fā)生發(fā)展中具有一定作用。4.血必凈注射液可能通過降低炎癥因子水平而發(fā)揮心肌保護作用。
[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- 偽 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 鹵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- 偽 level in sham operation group was significantly higher than that in control group. The concentration of TNF- 偽 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- 偽 in Xuebijing group was higher than that in control group and sham operation group. There was a positive correlation between serum TNF- 偽 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.
【學位授予單位】:天津醫(yī)科大學
【學位級別】:碩士
【學位授予年份】:2012
【分類號】:R459.7

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