發(fā)布時(shí)間：2018-05-06 00:06

  本文選題：丙泊酚 + 休克��； 參考：《河北醫(yī)科大學(xué)》2016年碩士論文

【摘要】：目的:失血性休克(Hemorrhagic shock,HS)常見(jiàn)于嚴(yán)重創(chuàng)傷和手術(shù)出血,是臨床上十分危急的病癥,若未經(jīng)及時(shí)治療,可導(dǎo)致死亡。HS主要以全身血容量驟減、組織灌注減少、細(xì)胞缺氧、無(wú)氧代謝增加及乳酸堆積,氧自由基和代謝產(chǎn)物生成增多為主要特征,造成細(xì)胞氧化應(yīng)激損傷,嚴(yán)重者可導(dǎo)致器官功能障礙,甚至衰竭。盡管心肌細(xì)胞對(duì)缺血缺氧有較強(qiáng)的耐受力,但嚴(yán)重休克時(shí)仍會(huì)表現(xiàn)為收縮功能下降、心輸出量減少,進(jìn)而加重其他臟器損傷。丙泊酚是臨床常用的靜脈麻醉藥,具有對(duì)抗氧自由基和抑制細(xì)胞凋亡的作用。研究表明丙泊酚對(duì)失血性休克和缺血-再灌注心肌損傷具有明顯的保護(hù)作用�？p隙連接蛋白43(Connexin 43,Cx43)是心肌細(xì)胞縫隙連接的主要蛋白,Cx43的空間分布、數(shù)量及磷酸化異常均可影響縫隙連接電耦聯(lián),影響心肌同步收縮功能。研究表明,急性心肌缺血后Cx43會(huì)發(fā)生重構(gòu),主要表現(xiàn)為蛋白表達(dá)下降,分布模式以及磷酸化的改變。本研究擬探討丙泊酚對(duì)失血性休克兔心肌損傷時(shí)Cx43表達(dá)的影響,為明確丙泊酚心肌保護(hù)的作用機(jī)制提供參考。方法:健康清潔級(jí)雄性新西蘭白兔24只,5~7月齡,體重2.5~3.0 kg,由河北醫(yī)科大學(xué)實(shí)驗(yàn)動(dòng)物中心提供。采用隨機(jī)數(shù)字表法,將其分為3組(n=8):假手術(shù)(S)組、失血性休克(HS)組及丙泊酚處理(P)組。取兔稱(chēng)重后置于兔籠中沿右側(cè)耳緣靜脈注射3%戊巴比妥鈉30mg/kg,麻醉成功后將兔仰臥位固定于手術(shù)臺(tái)上。手術(shù)部位備皮消毒,1%利多卡因浸潤(rùn)麻醉后剪開(kāi)頸部正中皮膚,分離氣管,行氣管切開(kāi)插管術(shù)(ID=3.0mm)并保留自主呼吸;分離右側(cè)頸總動(dòng)脈,用24G套管針插入右側(cè)頸總動(dòng)脈并用絲線(xiàn)固定,連接M1567A有創(chuàng)血壓測(cè)壓套裝,再與Philips G60多功能監(jiān)護(hù)儀連接持續(xù)監(jiān)測(cè)動(dòng)脈血壓(BP)和平均動(dòng)脈壓(MAP)。1%利多卡因浸潤(rùn)麻醉后于兔左、右側(cè)股三角區(qū)分別斜行3cm剪開(kāi)皮膚,暴露并分離雙側(cè)股動(dòng)靜脈,用24G套管針?lè)謩e置入左側(cè)股動(dòng)脈和右側(cè)股靜脈并用絲線(xiàn)固定,連接三通用于放血、采集動(dòng)脈血樣和輸血、給藥。置管完成后靜脈給予肝素鈉3mg/kg。S組僅行氣管切開(kāi)插管術(shù)、右側(cè)頸總動(dòng)脈和股動(dòng)靜脈穿刺置管術(shù),不放血;P組于放血前10min經(jīng)右側(cè)股靜脈注射丙泊酚5 mg/kg,并用微量注射泵以20mg·kg~(-1)·h~(-1)的速度持續(xù)輸注至休克后120min;S組及HS組靜脈輸注等容量生理鹽水。采用Wigger’s改良法經(jīng)左側(cè)股動(dòng)脈放血,10 min內(nèi)使MAP降至40mm Hg,放血量約為全身血容量的30~50%,觀察兔血壓波動(dòng),通過(guò)放血和回輸血液維持MAP在35~45 mm Hg之間以達(dá)休克狀態(tài)并維持120 min,制備失血性休克動(dòng)物模型。于放血前即刻(T_0)、休克30 min(T_1)、60 min(T_2)、90 min(T_3)和120min(T_4)采集動(dòng)脈血樣測(cè)定各時(shí)間點(diǎn)血漿cTnI濃度及動(dòng)脈血乳酸水平。于T_4采血后,連接HX-200動(dòng)物呼吸機(jī)行機(jī)械通氣,快速打開(kāi)胸腔,取心尖部心肌組織并一分為二,一半置于EP管中液氮凍存24h,再轉(zhuǎn)-80℃冰箱保存待測(cè);另一半組織用4 4%℃多聚甲醛溶液固定待測(cè)。采用ELISA法測(cè)定兔血漿cTnI濃度;采用自動(dòng)血?dú)夥治鰞x檢測(cè)動(dòng)脈血乳酸水平;取4%多聚甲醛溶液固定的心肌組織,常規(guī)石蠟包埋切片,HE染色,光學(xué)顯微鏡下觀察心肌病理?yè)p傷并行損傷評(píng)分;取-80℃冰箱凍存的心肌組織采用Western blot法檢測(cè)兔心肌組織Cx43表達(dá)。結(jié)果:1 與S組比較,HS組與P組兔血漿cTnI濃度升高(P0.05);與HS組比較,P組兔血漿cTnI濃度降低(P0.05);與T_0比較,HS組和P組T_(1-4)時(shí)兔血漿cTnI濃度逐漸升高(P0.05)。2 與S組比較,HS組與P組兔動(dòng)脈血乳酸水平升高(P0.05);與HS組比較,P組兔動(dòng)脈血乳酸水平降低(P0.05);與T_0比較,HS組和P組T_(1-4)時(shí)兔動(dòng)脈血乳酸水平逐漸升高(P0.05)。3 S組心肌細(xì)胞形態(tài)正常,肌纖維排列整齊,細(xì)胞核均勻一致;HS組心肌細(xì)胞腫脹,纖維排列不規(guī)則或斷裂,間質(zhì)內(nèi)有大量炎性細(xì)胞浸潤(rùn),胞核崩解;P組心肌細(xì)胞輕度變性,少量心肌纖維斷裂,細(xì)胞間隙略增寬,病理?yè)p傷較HS組減輕。與S組比較,HS組和P組心肌損傷評(píng)分升高(P0.05);與HS組比較,P組心肌損傷評(píng)分降低(P0.05)。4 與S組比較,HS組和P組心肌Cx43含量減少(P0.05);與HS組比較,P組心肌Cx43含量增加(P0.05)。結(jié)論:1 股動(dòng)脈放血法可成功制備失血性休克動(dòng)物模型。2 失血性休克可引起心肌損傷并使心肌細(xì)胞Cx43表達(dá)減少。3 丙泊酚可減輕失血性休克心肌損傷,其機(jī)制可能與上調(diào)Cx43表達(dá)有關(guān)。
[Abstract]:Objective: Hemorrhagic shock (HS) is common in severe trauma and surgical bleeding. It is a very critical disease in clinical. If not treated in time, the death.HS can lead to a sudden decrease in systemic blood volume, decreased tissue perfusion, anoxia, anoxic metabolism and lactic acid accumulation, and increased oxygen free radicals and metabolic products. It is characterized by oxidative stress caused by cell oxidative stress, which can cause organ dysfunction and even failure. Although myocardial cells have strong tolerance to ischemia and hypoxia, however, severe shock will still appear to be a decrease in systolic function, a decrease in cardiac output, and further aggravation of other organs. Propofol is a common clinical intravenous anesthetic. The study shows that propofol has a significant protective effect on myocardial damage in hemorrhagic shock and ischemia-reperfusion. Gap connexin 43 (Connexin 43, Cx43) is the main protein in the gap junction of cardiac myocytes. The spatial distribution, quantity and phosphorylation of Cx43 can affect the connexion of gap junction The study shows that Cx43 can be reconstructed after acute myocardial ischemia, mainly manifested in the decrease of protein expression, distribution pattern and the change of phosphorylation. This study intends to explore the effect of propofol on the expression of Cx43 during myocardial injury in rabbits with hemorrhagic shock, and to provide a clear mechanism for the protection of propofol myocardium. Methods: 24 healthy and clean male New Zealand white rabbits, 5~7 months old and weight 2.5~3.0 kg, were provided by the experimental animal center of Hebei Medical University. Using random digital table method, they were divided into 3 groups (n=8): sham operation (S) group, hemorrhagic shock (HS) group and propofol (P) group. After the rabbit was weighed, the rabbit was injected 3% into the right ear edge vein. After the success of pentobarbital sodium 30mg/kg, the rabbit supine position was fixed on the operating table after the anesthesia was successful. The surgical site was prepared by skin preparation and 1% lidocaine, after the infiltration of lidocaine, the median skin of the neck was cut, the trachea was separated, the tracheotomy intubation (ID=3.0mm) was performed and the spontaneous breathing was retained; the right common carotid artery was separated and the right common carotid artery was inserted with the 24G trocar and used silk thread. Fixation, connecting M1567A with a blood pressure pressure measurement kit, and the continuous monitoring of arterial pressure (BP) and the mean arterial pressure (MAP).1% lidocaine infiltration anesthesia with the Philips G60 multi function monitor in the left of the rabbit, the right femoral triangle slanting 3cm to cut off the skin, exposing and separating the bilateral femoral arteriovenous, and placing the left femoral artery with the 24G trocar needle respectively. The femoral vein and the right femoral vein were fixed with silk thread, connecting three to blood letting, collecting arterial blood samples and blood transfusion, giving the medicine. After the catheter was completed, the heparin sodium 3mg/kg.S group was given only tracheotomy intubation, the right common carotid artery and femoral arteriovenous catheterization were performed, and blood was not released; group P was injected 10min via the right femoral vein before releasing the blood, and the use of propofol was 5 mg/kg. The microinjection pump was injected at the speed of 20mg. Kg~ (-1) and h~ (-1) to 120min, 120min, S group and HS group intravenous infusion. Using Wigger 's improvement method, the left femoral artery was bleed to the left femoral artery, and the MAP was reduced to approximately 50% of the whole body blood volume in the 10 min. The blood pressure fluctuation was observed and maintained by blood letting and blood transfusion. MAP between 35~45 mm Hg and 120 min was used to produce hemorrhagic shock animal model. The plasma concentration and arterial blood lactate level at each time point were measured at immediately (T_0), shock 30 min (T_1), 60 min (T_2), 90 min (T_3) and arterial blood samples. Mechanical ventilation, quickly open the chest, take the apex of the myocardial tissue and divide into two, half of the liquid nitrogen in the EP tube in the EP tube to freeze 24h, then turn -80 C refrigerator to be kept for test; the other half of the tissue was fixed at 44% centigrade polycondensation. The ELISA method was used to determine the plasma cTnI concentration in the rabbit; the serum lactate level was detected by the automatic blood gas analyzer; and the concentration of the blood lactate was detected by the automatic blood gas analyzer. Formaldehyde Solution fixed myocardial tissue, conventional paraffin embedded section, HE staining, observation of myocardial pathological injury parallel injury score under optical microscope, and Western blot method was used to detect Cx43 expression of myocardium tissue in the myocardium of freezer at -80 C. Results: 1 compared with group S, the concentration of cTnI in HS group and P group increased (P0.05), and compared with HS group. Compared with the P group, the plasma concentration of cTnI decreased (P0.05). Compared with T_0, HS and P group T_ (1-4) increased the plasma cTnI concentration in rabbits (P0.05).2 and S group, and the level of lactic acid in the arterial blood of the rabbits was higher than that in the S group; compared with the group, the lactate level of the rabbit arterial blood decreased. In the group of.3 S, the myocardial cells were normal, the muscle fibers were arranged and the nuclei were uniform. The myocardial cells in the group HS were swollen, the fiber arrangement was irregular or broken. There were a large number of inflammatory cells infiltrating in the interstitium and the disintegration of the nucleus; the myocardial cells in the P group were slightly denatured, a small amount of myocardial fibers were broken, the gap of the cells increased slightly, and the pathological injury was less than that of the HS group. Compared with group S, myocardial injury scores in group HS and group P were increased (P0.05). Compared with group HS, myocardial injury score of P group decreased (P0.05).4 and S group, HS group and P group decreased. Conclusion: 1 femoral artery bleeding method can be successfully prepared for hemorrhagic shock animal model. Sexual shock can cause myocardial injury and reduce the expression of Cx43 in cardiac myocytes by.3 propofol, which may reduce myocardial injury in hemorrhagic shock, and its mechanism may be related to the up regulation of Cx43 expression.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R614

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本文編號(hào)：1849871