發(fā)布時間：2018-07-05 16:09

  本文選題：連續(xù)性血液凈化 + 多器官功能障礙綜合征　； 參考：《中國人民解放軍軍醫(yī)進(jìn)修學(xué)院》2007年碩士論文

【摘要】： 目的：利用失血性休克、缺血-再灌注損傷及內(nèi)毒素復(fù)合因素，模擬戰(zhàn)創(chuàng)傷特點(diǎn)建立豬的多器官功能障礙綜合征(multiple organ dysfunctionsyndrome，MODS)實驗?zāi)Ｐ停治鲅屑?xì)胞因子水平的變化，，探討早期實施連續(xù)性血液凈化(continuous blood purification，CBP)對戰(zhàn)創(chuàng)傷致MODS主要器官功能及細(xì)胞因子的影響。方法：16只健康雄性豬，隨機(jī)分為CBP組(n=6)和MODS組(n=10)。MODS組動物予放血總血容量的30～45％，維持2小時后開始液體復(fù)蘇，復(fù)蘇完畢后1小時予大腸桿菌內(nèi)毒素(E. coli O_(55)：B_5)按100ug／kg在4-6小時內(nèi)自外周靜脈持續(xù)泵入，模擬戰(zhàn)創(chuàng)傷特點(diǎn)建立MODS動物模型；CBP組于內(nèi)毒素注射1小時后開始CBP治療，采用高通量血液濾過(high-volume hemofiltration，HVHF)模式，治療16～18小時；連續(xù)動態(tài)監(jiān)測及器官功能支持，7天后處死存活動物。觀察各時間點(diǎn)的外周血細(xì)胞計數(shù)、動脈血?dú)饧爸饕鞴俟δ軈?shù)的變化，以ELISA法檢測血清血管內(nèi)皮生長因子(VEGF)、腫瘤壞死因子α(TNFα)、白介素-6(IL-6)、白介素-10(IL-10)的濃度，并觀察MODS發(fā)生率和死亡率及主要器官病理學(xué)改變，分析VEGF與主要器官功能參數(shù)及炎癥介質(zhì)等變化趨勢的相關(guān)性，比較存活與死亡動物的血清VEGF濃度，并比較CBP組與MODS組主要器官功能、血清細(xì)胞因子的水平及兩組的死亡率。結(jié)果：模型成功率70％，注射內(nèi)毒素1小時后TNFα、IL-6、IL-10均顯著升高，病理學(xué)改變主要以非特異炎癥改變?yōu)橹�。MODS死亡率達(dá)71.4％，發(fā)生3個器官功能障礙的有4例，發(fā)生4個或以上器官功能障礙的有3例，肺和胃腸衰竭的發(fā)生次數(shù)最多，而心臟衰竭及凝血功能障礙死亡率最高；在休克期及再灌注期血清VEGF水平升高，內(nèi)毒素打擊后明顯降低，血清VEGF水平的變化趨勢與AST、ALT、TBIL、Cr有負(fù)性相關(guān)(P＜0.05)，與外周血Plt變化趨勢呈正性相關(guān)(P＜0.05)，與TNFα、IL-6、 (TNFα+IL-6)／IL-10比值的變化趨勢亦有相關(guān)性(P＜0.05)，存活組血清VEGF水平高于死亡組(P＜0.05)；CBP組氧合指數(shù)高于MODS組，外周血AST、ALT、Cr明顯低于MODS組，但兩組外周血小板計數(shù)、血清TBIL濃度差異無統(tǒng)計學(xué)意義；CBP組血清TNFα、IL-6、IL-10水平均在CBP治療3～7小時左右下降明顯，之后逐漸升高接近于MODS組；CBP組治療后血清VEGF水平高于MODS組；CBP組死亡率為16.7％，顯著低于MODS組(71.4％)(P＜0.01)。結(jié)論：利用復(fù)合因素打擊，可以模擬戰(zhàn)創(chuàng)傷特點(diǎn)建立MODS動物模型，MODS時出現(xiàn)促炎／抗炎失衡，過度炎癥反應(yīng)可抑制VEGF的表達(dá)，血清VEGF水平與主要器官功能參數(shù)變化趨勢有相關(guān)性，在MODS的發(fā)展中可能具有防御機(jī)制；早期CBP干預(yù)治療能有效改善主要臟器功能，降低血中炎癥介質(zhì)水平，減弱炎癥反應(yīng)，可利于VEGF的表達(dá)，降低MODS的死亡率。
[Abstract]:Objective: to establish an experimental model of (multiple organ dysfunctional dysfunction syndrome (multiple organ dysfunctional syndrome mods) in pigs by using hemorrhagic shock, ischemia-reperfusion injury and endotoxin compound factors, and to analyze the changes of cytokines in blood. To investigate the effects of early continuous blood purification (continuous blood purificationus) on the function of major organs and cytokines of mods caused by war trauma. Methods Sixteen healthy male pigs were randomly divided into CBP group (n = 6) and mods group (n = 10). One hour after resuscitation, E. coli O _ (55: B _ 5) was continuously pumped into 100ug/kg from peripheral vein within 4-6 hours. The animal model of mods was established by simulating the characteristics of war trauma. The mods animal model was treated with 100ug/kg for 1 hour after endotoxin injection. The high-volume hemofiltration (HV) model was used to treat the animals for 16 to 18 hours, and the surviving animals were killed after 7 days of continuous dynamic monitoring and organ function support. The changes of peripheral blood cell count, arterial blood gas and main organ function parameters at different time points were observed. The serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor 偽 (TNF 偽), interleukin-6 (IL-6) and interleukin-10 (IL-10) were detected by Elisa. The incidence and mortality of mods and pathological changes of main organs were observed, and the correlation between VEGF and the changes of main organ function parameters and inflammatory mediators were analyzed, and the serum VEGF concentrations of surviving and dead animals were compared. The main organ function, serum cytokine level and mortality were compared between CBP group and mods group. Results: the success rate of the model was 70%. The level of IL-10 in TNF- 偽 and IL-6 was significantly increased 1 hour after endotoxin injection. The mortality rate of mods was 71.4%, and 4 cases had three organ dysfunction. There were 3 cases with 4 or more organ dysfunction, the incidence of pulmonary and gastrointestinal failure was the most frequent, the mortality of heart failure and coagulation dysfunction was the highest, and the level of serum VEGF increased during shock and reperfusion. Endotoxin was significantly reduced after hitting, There was a negative correlation between the level of serum VEGF and the level of TBILCr (P < 0.05), a positive correlation with the change trend of peripheral blood Plt (P < 0.05), and a change trend with the ratio of TNF 偽 IL-6, (TNF 偽 IL-6) / IL-10 (P < 0.05). The serum VEGF level in the survival group was higher than that in the dead group (P < 0.05). The oxygenation index of CBP group was higher than that of mods group, and the level of ASTtTncr in peripheral blood was significantly lower than that in mods group. However, there was no significant difference in peripheral platelet count and serum TBIL concentration between CBP group and CBP group. The level of serum VEGF in mods group was significantly higher than that in mods group (P < 0.01). The mortality rate of CBP group was significantly lower than that of mods group (71.4%) (P < 0.01). Conclusion: by using compound attack, the animal model of mods can be established by simulating the characteristics of war trauma. The imbalance of proinflammatory / anti-inflammatory was found in mods. Excessive inflammatory reaction could inhibit the expression of VEGF, and the level of serum VEGF was correlated with the change trend of main organ function parameters. Early CBP intervention therapy can effectively improve the main organ function, reduce the level of inflammatory mediators in blood, weaken the inflammatory response, which is conducive to the expression of VEGF and reduce the mortality of mods.
【學(xué)位授予單位】：中國人民解放軍軍醫(yī)進(jìn)修學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2007
【分類號】：R82

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