緩慢間斷顱內(nèi)加壓法致豬腦死亡后炎癥反應(yīng)及氧化應(yīng)激對(duì)心肌的影響
發(fā)布時(shí)間：2018-10-17 12:59
【摘要】：目的：本研究旨在通過(guò)緩慢間斷顱內(nèi)加壓法建立豬腦死亡模型,觀察豬腦死亡模型建立過(guò)程中顱內(nèi)壓及腦電圖變化,與麻醉狀態(tài)下實(shí)驗(yàn)動(dòng)物進(jìn)行比較,結(jié)合臨床表現(xiàn),完善實(shí)驗(yàn)動(dòng)物腦死亡判定標(biāo)準(zhǔn),提高豬腦死亡判定準(zhǔn)確率。檢測(cè)豬腦死亡和麻醉狀態(tài)下各時(shí)間段血清超氧化物歧化酶(SOD)、丙二醛(MDA)、白介素-6(IL-6)及單核細(xì)胞趨化蛋白-1(MCP-1)含量的變化。心肌組織檢查超氧化物歧化酶-1(SOD-1)和超氧化物歧化酶-2(SOD-2)的mRNA表達(dá)差異。心肌病理切片通過(guò)光學(xué)顯微鏡比較心肌細(xì)胞的變化情況。方法：6頭健康版納小耳豬隨機(jī)分為對(duì)照租(C組,3頭)和實(shí)驗(yàn)組(E組,3頭)兩組。兩組均經(jīng)耳緣靜脈行全身麻醉后行氣管切開(kāi)插管、呼吸機(jī)輔助呼吸、頸內(nèi)動(dòng)靜脈插管和膀胱造瘺術(shù)。對(duì)照組在此基礎(chǔ)上僅通過(guò)呼吸、循環(huán)支持維持麻醉狀態(tài)10h；實(shí)驗(yàn)組在此基礎(chǔ)上通過(guò)緩慢間斷顱內(nèi)加壓法建立腦死亡模型,即行顱骨鉆孔術(shù)并將Foley18F氣囊導(dǎo)管和顱內(nèi)壓監(jiān)測(cè)導(dǎo)線置于硬腦膜下腔,通過(guò)Foley氣囊導(dǎo)管緩慢向硬腦膜下腔內(nèi)注入約30-40ml生理鹽水以增加顱內(nèi)壓造成腦疝,建立腦死亡模型維持10h并持續(xù)監(jiān)測(cè)顱內(nèi)壓變化。實(shí)驗(yàn)過(guò)程中詳細(xì)記錄用藥量、用藥時(shí)間、心率、心電圖、血壓、尿量及顱內(nèi)壓的變化情況。兩組實(shí)驗(yàn)過(guò)程中除是否建立腦死亡模型外,其他實(shí)驗(yàn)條件均相同。對(duì)照組在建模完成后分別于0.5、2、4、6、8、10h抽取靜脈血6ml用酶聯(lián)免疫吸附測(cè)定法(ELIAS)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；實(shí)驗(yàn)組在腦死亡模型建立后分別于0.5、2、4、6、8、10h抽取靜脈血16ml用酶聯(lián)免疫吸附測(cè)定法(ELIAS)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；兩組實(shí)驗(yàn)動(dòng)物在維持10h后撤除呼吸、循環(huán)支持,開(kāi)胸取心內(nèi)膜下心肌組織,檢測(cè)心肌超氧化物歧化酶-1(SOD-1)和超氧化物歧化酶-2(SOD-2) mRNA的表達(dá)情況和心肌細(xì)胞光學(xué)顯微鏡檢查。 結(jié)果： 1.對(duì)照組3頭實(shí)驗(yàn)動(dòng)物在麻醉狀態(tài)下通過(guò)呼吸、循環(huán)支持,全部存活10h,實(shí)驗(yàn)成功率100%；實(shí)驗(yàn)組3頭實(shí)驗(yàn)動(dòng)物的腦死亡模型建立成功率100%,術(shù)后10h存活率100%;共6頭豬用于課題研究。 2.血流動(dòng)力學(xué)和強(qiáng)心藥物的用量：對(duì)照組在實(shí)驗(yàn)過(guò)程中心功能未見(jiàn)明顯下降,有創(chuàng)動(dòng)脈血壓檢測(cè)未見(jiàn)明顯變化,僅隨麻醉深度變化產(chǎn)生波動(dòng),未使用任何強(qiáng)心、血管活性藥物；實(shí)驗(yàn)組在通過(guò)緩慢間斷顱內(nèi)加壓法建立豬腦死亡模型后,隨著心功能的逐漸下降,有創(chuàng)動(dòng)脈血壓降低、心率下降,呈低血壓狀態(tài),需用強(qiáng)心、血管活性藥物如腎上腺素、多巴胺等才能維持基礎(chǔ)血壓,且實(shí)驗(yàn)后期用藥量及用藥頻率較前期高。 3.血清IL-6：實(shí)驗(yàn)組在腦死亡第2h后血清IL-6較對(duì)照組明顯升高,兩組對(duì)比有顯著性差異(P0.05)。 4.血清MCP-1：實(shí)驗(yàn)組在腦死亡第2h后血清MCP-I較對(duì)照組明顯升高,兩組對(duì)比有顯著性差異(P0.05)。 5.血清SOD：實(shí)驗(yàn)組在腦死亡后血清SOD較對(duì)照組明顯升高,兩組對(duì)比有顯著性差異(P0.05)。 6.血清MDA：實(shí)驗(yàn)組在腦死亡后血清MDA較對(duì)照組明顯升高,兩組對(duì)比有顯著性差異(P0.05) 7.心肌組織SOD-1mRNA和SOD-2mRNA:實(shí)驗(yàn)組較對(duì)照組心臟組織SODmRNA的表達(dá)均明顯升高,表達(dá)水平變化具有顯著性差異(P0.05)。 8.心肌組織光鏡：對(duì)照組未見(jiàn)明顯異常；實(shí)驗(yàn)組可見(jiàn)心肌間質(zhì)水腫,心肌間質(zhì)血管收縮,炎細(xì)胞侵潤(rùn),局部可見(jiàn)心肌細(xì)胞溶解壞死。 結(jié)論： 1.本實(shí)驗(yàn)應(yīng)用緩慢間斷顱內(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(guò)程,經(jīng)有效的呼吸、循環(huán)支持,腦死亡狀態(tài)可穩(wěn)定維持。 2.將動(dòng)態(tài)腦電圖檢測(cè)、動(dòng)態(tài)顱內(nèi)壓檢測(cè)應(yīng)用于腦死亡模型建立的判定,在實(shí)驗(yàn)中可行。 3.心功能下降是腦死亡后心臟重要的病理生理改變。兩組結(jié)果進(jìn)行分析、比較,以非腦死亡狀態(tài)為參照,能更好的了解腦死亡狀態(tài)下心臟功能的改變情況及意義。 4.腦死亡狀態(tài)下,血清SOD、MDA、IL-6及MCP-1含量均有明顯升高。 5.腦死亡狀態(tài)下,心肌細(xì)胞內(nèi)SOD-1mRNA、SOD-2mRNA含量均升高。
[Abstract]:Objective: The aim of this study was to establish the model of pig brain death by slow intermittent intracranial pressure method, observe the changes of intracranial pressure and EEG during the establishment of pig brain death model, compare with the experimental animals under the anesthesia state, combine the clinical manifestation, improve the experimental animal brain death judgment standard, improve that accuracy rate of the determination of the brain death of the pig. The changes of serum superoxide dismutase (SOD), (MDA), interleukin-6 (IL-6) and monocyte chemotaxis protein-1 (MCP-1) in pig brain death and anesthesia were detected. The mRNA expression of superoxide dismutase-1 (SOD-1) and superoxide dismutase-2 (SOD-2) was examined by myocardial tissue. The changes of cardiac myocytes were compared by optical microscope. Methods: Six healthy and small ear pigs were randomly divided into two groups: control group (group C, 3 head) and experimental group (group E, head 3). Both groups underwent tracheotomy intubation, ventilator-assisted respiration, internal jugular vein cannulation and cystostomy after systemic anesthesia. In the control group, the anesthesia state was maintained only by breathing and circulatory support, and the experimental group established the brain death model through the slow intermittent intracranial pressure method, namely, the skull drilling operation and the Foley18F balloon catheter and the intracranial pressure monitoring lead were placed in the subdural cavity. Approximately 30-40ml of physiological saline was injected slowly into the subdural cavity through the Foley balloon catheter to increase intracranial pressure to cause brain hernia, establish a brain death model for 10h and continuously monitor intracranial pressure changes. The changes of dosage, medication time, heart rate, electrocardiogram, blood pressure, heart rate and intracranial pressure were recorded in detail in the experiment. Except for the establishment of brain death model, the other experimental conditions were the same in both groups. In the control group, serum superoxide dismutase (SOD, MDA, IL-6, monocyte chemotaxis protein-1) were detected at 0. 5, 2, 4, 6, 8, and 10 h after the modeling was completed. In the experimental group, the serum superoxide dismutase (SOD, MDA, IL-6, monocyte chemotaxis protein-1) were detected with enzyme-linked immunosorbent assay (ELIAS) after the brain death model was established. The expression of superoxide dismutase-1 (SOD-1) and superoxide dismutase-2 (SOD-2) mRNA and optical microscope examination of cardiac myocytes were detected in the open chest. Results: 1. Three experimental animals in the control group were able to survive for 10h under the anesthesia state, the success rate was 100%, the success rate of brain death was 100%, the survival rate was 100% after operation, and 6 pigs were used in the experiment group. 2. Hemodynamics and dose of antiepileptic drugs: In the control group, there was no significant decrease in the function of the central function of the experimental process, and there was no obvious change in the blood pressure of invasive artery, but only with the change of the depth of anesthesia, and no strong use was used. Heart and blood vessel active drugs; in the experimental group, after the pig brain death model was established by the slow intermittent intracranial injection method, with the decrease of cardiac function, the invasive arterial blood pressure decreased, the heart rate was decreased, the blood pressure was low, and the blood vessels, vasoactive drugs such as epinephrine, dopamine, etc. were needed. the basal blood pressure can be maintained, and the dosage in the later period of the experiment and The serum IL-6 in the experimental group was significantly higher than that in the control group after the brain death, and the contrast between the two groups was significantly higher than that in the control group. The serum MCP-1 in the experimental group was significantly higher than that in the control group after brain death. Compared with the control group, the serum SOD in the experimental group was significantly higher than that in the control group. There was a significant difference between the two groups (P0.05). Serum MDA: the serum MDA in the experimental group after brain death was lower than that in the control group. The levels of SOD-1mRNA and SOD-2mRNA in myocardium were significantly higher than that in control group (P <0.05). There was a significant difference in the changes of expression level (P <0.05). 8. Myocardial tissue light microscope: no obvious abnormality was found in the control group. intermuscular stroma Conclusion: 1. The model of brain death of pig is established by slow intermittent intracranial pressure method in this experiment. The development of bed brain death can be stably maintained by effective breathing, circulatory support and brain death. Dynamic EEG detection and dynamic intracranial pressure detection applied to brain death model building 3. The decrease of cardiac function is the important pathophysiological change of the heart after brain death. Compared with the non-brain death status, it can better understand the changes of cardiac function in brain death and its significance.. 4. The levels of SOD, MDA, IL-6 and MCP-1 in serum were significant in the state of 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(lèi)號(hào)】：R654.2
本文編號(hào)：2276730
[Abstract]:Objective: The aim of this study was to establish the model of pig brain death by slow intermittent intracranial pressure method, observe the changes of intracranial pressure and EEG during the establishment of pig brain death model, compare with the experimental animals under the anesthesia state, combine the clinical manifestation, improve the experimental animal brain death judgment standard, improve that accuracy rate of the determination of the brain death of the pig. The changes of serum superoxide dismutase (SOD), (MDA), interleukin-6 (IL-6) and monocyte chemotaxis protein-1 (MCP-1) in pig brain death and anesthesia were detected. The mRNA expression of superoxide dismutase-1 (SOD-1) and superoxide dismutase-2 (SOD-2) was examined by myocardial tissue. The changes of cardiac myocytes were compared by optical microscope. Methods: Six healthy and small ear pigs were randomly divided into two groups: control group (group C, 3 head) and experimental group (group E, head 3). Both groups underwent tracheotomy intubation, ventilator-assisted respiration, internal jugular vein cannulation and cystostomy after systemic anesthesia. In the control group, the anesthesia state was maintained only by breathing and circulatory support, and the experimental group established the brain death model through the slow intermittent intracranial pressure method, namely, the skull drilling operation and the Foley18F balloon catheter and the intracranial pressure monitoring lead were placed in the subdural cavity. Approximately 30-40ml of physiological saline was injected slowly into the subdural cavity through the Foley balloon catheter to increase intracranial pressure to cause brain hernia, establish a brain death model for 10h and continuously monitor intracranial pressure changes. The changes of dosage, medication time, heart rate, electrocardiogram, blood pressure, heart rate and intracranial pressure were recorded in detail in the experiment. Except for the establishment of brain death model, the other experimental conditions were the same in both groups. In the control group, serum superoxide dismutase (SOD, MDA, IL-6, monocyte chemotaxis protein-1) were detected at 0. 5, 2, 4, 6, 8, and 10 h after the modeling was completed. In the experimental group, the serum superoxide dismutase (SOD, MDA, IL-6, monocyte chemotaxis protein-1) were detected with enzyme-linked immunosorbent assay (ELIAS) after the brain death model was established. The expression of superoxide dismutase-1 (SOD-1) and superoxide dismutase-2 (SOD-2) mRNA and optical microscope examination of cardiac myocytes were detected in the open chest. Results: 1. Three experimental animals in the control group were able to survive for 10h under the anesthesia state, the success rate was 100%, the success rate of brain death was 100%, the survival rate was 100% after operation, and 6 pigs were used in the experiment group. 2. Hemodynamics and dose of antiepileptic drugs: In the control group, there was no significant decrease in the function of the central function of the experimental process, and there was no obvious change in the blood pressure of invasive artery, but only with the change of the depth of anesthesia, and no strong use was used. Heart and blood vessel active drugs; in the experimental group, after the pig brain death model was established by the slow intermittent intracranial injection method, with the decrease of cardiac function, the invasive arterial blood pressure decreased, the heart rate was decreased, the blood pressure was low, and the blood vessels, vasoactive drugs such as epinephrine, dopamine, etc. were needed. the basal blood pressure can be maintained, and the dosage in the later period of the experiment and The serum IL-6 in the experimental group was significantly higher than that in the control group after the brain death, and the contrast between the two groups was significantly higher than that in the control group. The serum MCP-1 in the experimental group was significantly higher than that in the control group after brain death. Compared with the control group, the serum SOD in the experimental group was significantly higher than that in the control group. There was a significant difference between the two groups (P0.05). Serum MDA: the serum MDA in the experimental group after brain death was lower than that in the control group. The levels of SOD-1mRNA and SOD-2mRNA in myocardium were significantly higher than that in control group (P <0.05). There was a significant difference in the changes of expression level (P <0.05). 8. Myocardial tissue light microscope: no obvious abnormality was found in the control group. intermuscular stroma Conclusion: 1. The model of brain death of pig is established by slow intermittent intracranial pressure method in this experiment. The development of bed brain death can be stably maintained by effective breathing, circulatory support and brain death. Dynamic EEG detection and dynamic intracranial pressure detection applied to brain death model building 3. The decrease of cardiac function is the important pathophysiological change of the heart after brain death. Compared with the non-brain death status, it can better understand the changes of cardiac function in brain death and its significance.. 4. The levels of SOD, MDA, IL-6 and MCP-1 in serum were significant in the state of 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(lèi)號(hào)】：R654.2
【參考文獻(xiàn)】
相關(guān)期刊論文 前10條
1 龍建綱,王學(xué)敏,高宏翔,劉昌盛,劉志,繆明永,劉健康;丙二醛對(duì)大鼠肝線粒體呼吸功能及相關(guān)脫氫酶活性影響[J];第二軍醫(yī)大學(xué)學(xué)報(bào);2005年10期
2 胡曉晴,唐娜;體感誘發(fā)電位的基本原理[J];國(guó)外醫(yī)學(xué)(物理醫(yī)學(xué)與康復(fù)學(xué)分冊(cè));2005年02期
3 郭旗;周遷權(quán);肖水源;;腦死亡判定和確診性實(shí)驗(yàn)的方法學(xué)[J];吉林醫(yī)學(xué);2010年22期
4 劉南平;陳景云;周立明;林樹(shù)敏;;腦電圖、經(jīng)顱多普勒超聲、體感誘發(fā)電位檢測(cè)對(duì)昏迷患者腦功能評(píng)判的價(jià)值[J];臨床神經(jīng)病學(xué)雜志;2009年01期
5 凌鋒;;腦死亡判定標(biāo)準(zhǔn)(成人)(修訂稿)[J];中國(guó)腦血管病雜志;2009年04期
6 胡克琦,陳謙學(xué),葉應(yīng)湖;腦死亡病人的腦電圖監(jiān)測(cè)[J];中國(guó)臨床神經(jīng)外科雜志;2003年02期
7 張賽;亞低溫腦保護(hù)的研究進(jìn)展[J];中國(guó)綜合臨床;2003年04期
8 張水軍,史冀華,崔雪艷,李捷,李震;顱內(nèi)加壓法巴馬小型豬腦死亡模型建立過(guò)程中血壓和心率的變化[J];中華實(shí)驗(yàn)外科雜志;2005年04期
9 李舜偉,張國(guó)瑾;國(guó)外腦死亡研究近況[J];中華醫(yī)學(xué)雜志;2003年20期
10 ;器官移植供體短缺之解決途徑:器官捐獻(xiàn)[J];中國(guó)組織工程研究與臨床康復(fù);2010年53期
，本文編號(hào)：2276730
本文鏈接：http://www.sikaile.net/yixuelunwen/mazuiyixuelunwen/2276730.html
最近更新
教材專(zhuān)著
