本文選題：急性腦死亡　切入點：心肌損傷　出處：《昆明醫(yī)科大學》2014年碩士論文

【摘要】：目的：本研究旨在通過快速顱內加壓法建立豬急性腦死亡模型并在無藥物干預情況下觀察豬腦死亡和非腦死亡血清中超氧化物歧化酶(SOD)、丙二醛(MDA)、白介素6(IL-6)、單核細胞趨化蛋白1(MCP-1)等含量的變化。心肌組織檢查超氧化物歧化酶(SOD) mRNA的表達。心肌病理切片觀察心肌細胞的變化,對心率,腦電圖、顱內壓、平均動脈壓進行評估,并探討氧自由基對豬急性腦死亡心臟供體的影響。 方法：6頭健康版納小耳豬隨機分為2組(n=3),實驗組(A組)和對照組(B組),。實驗組靜脈全身麻醉后行氣管切開插管,呼吸機輔助呼吸,膀胱造瘺、頸內動靜脈插管、在右側顱骨矢狀線外側0.2—0.5cm處和左側顱骨矢狀線與冠裝線交界部的外上2/3,距離矢狀線0.2cm處各鉆一個直徑約lcm的孔,一根Foley18F氣囊導尿管由右側孔置入硬腦膜下腔內,向左側氣囊導尿管中以2m1/s注入25—40m1生理鹽水,逐漸膨脹氣囊,增加顱內壓,注水時間在1分鐘內,Foley氣囊導管加壓建立急性腦死亡模型并維持10h,左側將顱內壓傳感導線沿鉆孔進入硬腦膜下腔,記錄和觀察腦死亡前后顱內壓變化。對照組行靜脈全身麻醉和氣管插管,膀胱造瘺、頸內動靜脈插管后給予0.9%生理鹽水和麻醉藥物維持。實驗組在建立急性腦死亡模型后,應用0.9%生理鹽水和多巴胺維持CVP為5-10cmH2O, MAP為60mmHg-90mmHg。若發(fā)生尿崩癥應用抗利尿激素,所用藥量、時間及尿量詳細記錄。實驗組和對照組實驗過程中其他都相同,但只有實驗組建立急性腦死亡模型。應用快速顱內加壓法建立腦死亡模型,通過呼吸、循環(huán)支持維持實驗動物腦死亡狀態(tài)10小時,10小時后撤除呼吸、循環(huán)支持。A B兩組實驗動物分別在0.5h、2h、4h、6h、8h、10h內取動脈血6ml檢測血清超氧化物歧化酶、丙二醛、白介素6、單核細胞趨化蛋白1的含量。在腦死亡0.5h、2h、4h、6h、8h、10h檢測心率、心電圖、腦電圖、平均動脈壓,實驗末期取左心室心肌組織2塊各約1.0g分別保存?zhèn)溆谩?結果： 1.在通過快速顱內加壓法建立豬腦死亡模型中,6頭豬手術成100%,術后10h模型成活率90%,造模型過程中死亡1頭,5頭豬用于課題研究。失敗原因在實驗過程中頻發(fā)室顫搶救無效死亡。 2.血流動力學和強心藥物的用量：實驗組在通過快速顱內加壓法建立豬腦死亡模型后,后期隨著心功能的逐漸下降,平均動脈壓(MAP)降低,中心靜脈壓(CVP)升高,呈低血壓狀態(tài),需用血管活性藥物多巴胺才能維持基礎血壓。實驗組在豬腦死亡模型建立后,多巴胺用量比對照組明顯增多,腦死亡狀態(tài)心率較對照明顯減慢。 3血清SOD活性變化：實驗組較對照組血清SOD水平增高。實驗組和對照組血清SOD水平變化在0.5h、6h、8h具有顯著性差異(P0.05)。 4血清MDA含量變化：實驗組較對照組血清MDA含量增高。實驗組和對照組血清MDA含量變化在8h、10h具有顯著差異(P0.05)。 5血清IL-6活性變化：實驗組與對照組在10h高于對照組。實驗組和對照組血清IL-6活性變化具有顯著差異(P0.05)。 6血清MCP-1活性變化：實驗組與對照組在10h高于對照組。兩組MCP-1存在顯著差異(P0.05)。 7心肌SODmRNA表達：實驗組SOD1和SOD2明顯高于對照組,實驗組和對照組SODmRNA表達具有顯著差異(P0.05)。 8心肌組織光鏡下觀察：實驗組心肌間質水腫,部分心肌纖維顆粒變性,心肌間質血管呈收縮狀態(tài),肌纖維水樣變性,炎細胞浸潤,肌纖維斷裂。對照組心肌纖維排列整齊,橫紋清晰。實驗組與對照組具有顯著差異。 結論： 1.應用快速顱內加壓法建立豬腦死亡模型,比較符合臨床腦死亡的發(fā)展過程,經(jīng)有效的呼吸和循環(huán)支持,急性腦死亡狀態(tài)可穩(wěn)定維持。 2.心功能下降是腦死亡后心臟重要的病理生理特征,急性腦死亡可導致豬心肌組織損傷,并可出現(xiàn)心肌細胞形態(tài)學改變。 3.運用腦電圖和顱內壓檢測能夠增加對急性腦死亡判定的準確性。 4.急性腦死亡后MDA和IL-6MCP-1的生成增加,SOD能夠清除氧自由基并減少生物膜的脂質過氧化和炎癥因子的生成。 5.急性腦死亡過程中心肌SODmRNA高度表達,表明急性腦死亡狀態(tài)下心肌存在自我抗氧化功能。
[Abstract]:Objective : To study the changes of superoxide dismutase ( SOD ) , malondialdehyde ( MDA ) , interleukin - 6 ( IL - 6 ) and monocyte chemoattractant protein 1 ( MCP - 1 ) in swine with acute brain death by rapid intracranial pressure method .

Methods : Six healthy volunteers were randomly divided into 2 groups ( n = 3 ) , experimental group ( group A ) and control group ( group B ) . In the experimental group , 0 . 9 % normal saline and 0 . 9 % saline were injected into the lower cavity of the left cranial base . The results were as follows : 1 minute , 2 h , 4 h , 6 h , 8 h , 10 h .

Results :

1 . In the swine brain death model established by rapid intracranial pressure method , 6 pigs were operated at 100 % , the survival rate of 10 hours after operation was 90 % , 1 head was died in the model process and 5 pigs were used for the subject research .

2 . The blood flow dynamics and the dosage of cardiotonic medicine : The experimental group , after establishing the porcine brain death model by rapid intracranial pressure method , decreased the average arterial pressure ( MAP ) and the central venous pressure ( CVP ) in the later stage .

The serum SOD activity of the experimental group was higher than that in the control group . The changes of serum SOD level in the experimental group and the control group were significantly different at 0.5h , 6h and 8h ( P0.05 ) .

The content of MDA in serum of the experimental group was higher than that in the control group , and the content of MDA in the experimental group and the control group was significantly higher than that in the control group ( P0.05 ) .

Serum IL - 6 activity in experimental group and control group were significantly higher than those in control group ( P0.05 ) .

Serum MCP - 1 activity was significantly different between the experimental group and the control group ( P < 0.05 ) .

7 . SODmRNA expression in myocardium : SOD1 and SOD2 in experimental group were significantly higher than those in control group , and the expression of SODmRNA in experimental group and control group was significantly different ( P0.05 ) .

Under the microscope of myocardial tissue , the myocardial interstitial edema , partial cardiac muscle fiber granule degeneration , myocardial interstitial vessels were contracted , myofiber water - like degeneration , inflammatory cell infiltration and muscle fiber breakage were observed in the experimental group .

Conclusion :

1 . The swine brain death model was established by rapid intracranial pressure method , and the development process of clinical brain death was compared with that of clinical brain death , and the acute brain death status could be maintained stably through effective breathing and circulatory support .

2 . The decline of cardiac function is an important pathological characteristic of heart after brain death , and acute brain death can lead to injury of myocardial tissue of pig , and the morphological change of myocardial cells can occur .

3 . The accuracy of determination of acute brain death can be increased by using EEG and ICP .

4 . The production of MDA and IL - 6MCP - 1 increased after acute brain death , and SOD was able to scavenge oxygen free radicals and reduce lipid peroxidation and inflammatory factors .

5 . The expression of SODmRNA in the myocardium during acute brain death indicates that there is a self - oxidation function in the myocardium in the state of acute brain death .

【學位授予單位】：昆明醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R654.2

【參考文獻】

相關期刊論文 前10條

1 龍建綱,王學敏,高宏翔,劉昌盛,劉志,繆明永,劉健康;丙二醛對大鼠肝線粒體呼吸功能及相關脫氫酶活性影響[J];第二軍醫(yī)大學學報;2005年10期

2 陳雯;劉寧;張穎;齊迎春;楊靖;鄧昭陽;李曉玲;謝曉華;;硫化氫通過抑制炎性細胞因子及氧化應激保護大鼠骨骼肌缺血再灌注的心肌損傷[J];南方醫(yī)科大學學報;2013年04期

3 陳雯;張穎;齊迎春;任青愛;楊靖;鄧昭陽;謝曉華;;硫化氫對大鼠骨骼肌缺血再灌注所致心肌損傷的保護作用[J];中華保健醫(yī)學雜志;2011年03期

4 林春喜;林建聰;郭潤民;沈寧;馮鑒強;鄭東誕;;硫化氫通過調控JNK通路對抗高糖誘導的心肌細胞氧化應激損傷[J];中國動脈硬化雜志;2013年01期

5 張?zhí)戾a;對“腦死亡”診斷標準的認識[J];中華神經(jīng)外科疾病研究雜志;2003年02期

6 程希富;馬康華;;單核細胞趨化蛋白-1與心肌缺血再灌注損傷的關系[J];心血管病學進展;2008年02期

7 ;成人腦死亡判定標準(2009版)[J];疑難病雜志;2009年05期

8 張水軍;朱盛興;李捷;馬秀現(xiàn);馮留順;范正軍;;腦死亡對巴馬小型豬心臟結構與功能的影響及其機制的實驗研究[J];中國病理生理雜志;2007年08期

9 朱濤,楊樹源,姚智;白細胞介素-1與腦創(chuàng)傷[J];中華創(chuàng)傷雜志;1997年05期

10 ;腦死亡判定標準(成人)(征求意見稿)[J];中華神經(jīng)外科雜志;2003年02期

，

本文編號：1673471