發(fā)布時(shí)間：2018-03-27 22:11

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

【摘要】：目的：本研究旨在通過快速顱內(nèi)加壓法建立豬急性腦死亡模型并在無藥物干預(yù)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(xì)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(dá)。心肌病理切片觀察心肌細(xì)胞的變化,對(duì)心率,腦電圖、顱內(nèi)壓、平均動(dòng)脈壓進(jìn)行評(píng)估,并探討氧自由基對(duì)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(jī)分為2組(n=3),實(shí)驗(yàn)組(A組)和對(duì)照組(B組),。實(shí)驗(yàn)組靜脈全身麻醉后行氣管切開插管,呼吸機(jī)輔助呼吸,膀胱造瘺、頸內(nèi)動(dòng)靜脈插管、在右側(cè)顱骨矢狀線外側(cè)0.2—0.5cm處和左側(cè)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(gè)直徑約lcm的孔,一根Foley18F氣囊導(dǎo)尿管由右側(cè)孔置入硬腦膜下腔內(nèi),向左側(cè)氣囊導(dǎo)尿管中以2m1/s注入25—40m1生理鹽水,逐漸膨脹氣囊,增加顱內(nèi)壓,注水時(shí)間在1分鐘內(nèi),Foley氣囊導(dǎo)管加壓建立急性腦死亡模型并維持10h,左側(cè)將顱內(nèi)壓傳感導(dǎo)線沿鉆孔進(jìn)入硬腦膜下腔,記錄和觀察腦死亡前后顱內(nèi)壓變化。對(duì)照組行靜脈全身麻醉和氣管插管,膀胱造瘺、頸內(nèi)動(dòng)靜脈插管后給予0.9%生理鹽水和麻醉藥物維持。實(shí)驗(yàn)組在建立急性腦死亡模型后,應(yīng)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(yīng)用抗利尿激素,所用藥量、時(shí)間及尿量詳細(xì)記錄。實(shí)驗(yàn)組和對(duì)照組實(shí)驗(yàn)過程中其他都相同,但只有實(shí)驗(yàn)組建立急性腦死亡模型。應(yīng)用快速顱內(nèi)加壓法建立腦死亡模型,通過呼吸、循環(huán)支持維持實(shí)驗(yàn)動(dòng)物腦死亡狀態(tài)10小時(shí),10小時(shí)后撤除呼吸、循環(huán)支持。A B兩組實(shí)驗(yàn)動(dòng)物分別在0.5h、2h、4h、6h、8h、10h內(nèi)取動(dòng)脈血6ml檢測(cè)血清超氧化物歧化酶、丙二醛、白介素6、單核細(xì)胞趨化蛋白1的含量。在腦死亡0.5h、2h、4h、6h、8h、10h檢測(cè)心率、心電圖、腦電圖、平均動(dòng)脈壓,實(shí)驗(yàn)?zāi)┢谌∽笮氖倚募〗M織2塊各約1.0g分別保存?zhèn)溆谩?結(jié)果： 1.在通過快速顱內(nèi)加壓法建立豬腦死亡模型中,6頭豬手術(shù)成100%,術(shù)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(shí)驗(yàn)過程中頻發(fā)室顫搶救無效死亡。 2.血流動(dòng)力學(xué)和強(qiáng)心藥物的用量：實(shí)驗(yàn)組在通過快速顱內(nèi)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(dòng)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(chǔ)血壓。實(shí)驗(yàn)組在豬腦死亡模型建立后,多巴胺用量比對(duì)照組明顯增多,腦死亡狀態(tài)心率較對(duì)照明顯減慢。 3血清SOD活性變化：實(shí)驗(yàn)組較對(duì)照組血清SOD水平增高。實(shí)驗(yàn)組和對(duì)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(shí)驗(yàn)組較對(duì)照組血清MDA含量增高。實(shí)驗(yàn)組和對(duì)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(shí)驗(yàn)組與對(duì)照組在10h高于對(duì)照組。實(shí)驗(yàn)組和對(duì)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(shí)驗(yàn)組與對(duì)照組在10h高于對(duì)照組。兩組MCP-1存在顯著差異(P0.05)。 7心肌SODmRNA表達(dá)：實(shí)驗(yàn)組SOD1和SOD2明顯高于對(duì)照組,實(shí)驗(yàn)組和對(duì)照組SODmRNA表達(dá)具有顯著差異(P0.05)。 8心肌組織光鏡下觀察：實(shí)驗(yàn)組心肌間質(zhì)水腫,部分心肌纖維顆粒變性,心肌間質(zhì)血管呈收縮狀態(tài),肌纖維水樣變性,炎細(xì)胞浸潤(rùn),肌纖維斷裂。對(duì)照組心肌纖維排列整齊,橫紋清晰。實(shí)驗(yàn)組與對(duì)照組具有顯著差異。 結(jié)論： 1.應(yīng)用快速顱內(nèi)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(dǎo)致豬心肌組織損傷,并可出現(xiàn)心肌細(xì)胞形態(tài)學(xué)改變。 3.運(yùn)用腦電圖和顱內(nèi)壓檢測(cè)能夠增加對(duì)急性腦死亡判定的準(zhǔn)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(zhì)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(dá),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(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R654.2

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