深低溫停循環(huán)后急性腎損傷的危險因素和機(jī)制初探
發(fā)布時間：2018-08-12 14:11
【摘要】：目的：回顧性分析深低溫停循環(huán)下行全主動脈弓置換術(shù)患者的臨床資料,探索全主動脈弓置換術(shù)后急性腎損傷的圍術(shù)期危險因素。 方法：通過分析我院2012年6月至2013年6月期間,深低溫停循環(huán)下行全主動脈弓置換術(shù)患者的臨床數(shù)據(jù),使用RIFLE標(biāo)準(zhǔn)定義急性腎損傷及其損傷程度,將患者分為非急性腎損傷組(腎功能正常組)和急性腎損傷組(包括風(fēng)險期、損傷期、衰竭期),比較兩組患者圍術(shù)期各項(xiàng)臨床指標(biāo),計算患者深低溫停循環(huán)下全主動脈弓置換術(shù)后急性腎損傷的發(fā)生率,并通過Logistic回歸分析找出急性腎損傷的圍術(shù)期危險因素。 結(jié)果：共入選130例患者,年齡(48.8±10.0)歲,其中男性94例(72.3%)。術(shù)后有67例(51.5%)的患者處于損傷期或衰竭期,其中共17例(13.1%)患者行術(shù)后血液透析治療。多因素Logistic回歸分析結(jié)果顯示：患者年齡(OR=1.055,95%CI=1.003-1.110,P=0.039)、術(shù)前診斷為主動脈夾層(OR=21.770,95%CI=1.888-251.050, P=0.014)及圍術(shù)期紅細(xì)胞輸入總量(OR=1.108,95%CI=.1.002-1.225, P=0.046)是全主動脈弓置換術(shù)后發(fā)生急性腎損傷的獨(dú)立危險因素。 結(jié)論：深低溫停循環(huán)下行全主動脈弓置換術(shù)后急性腎損傷的發(fā)生率較高,其中需要臨床干預(yù)的發(fā)生率為51.5%(包括損傷期和衰竭期)�；颊吣挲g、術(shù)前診斷為主動脈夾層及圍術(shù)期紅細(xì)胞輸入總量是全主動脈弓置換術(shù)后發(fā)生急性腎損傷的獨(dú)立危險因素。 目的 1.明確深低溫停循環(huán)(DHCA, deep hypothermia circulatory arrest)是否可導(dǎo)致急性腎損傷(AKI, acute kidney injury)。 2.探討深低溫停循環(huán)后急性腎損傷與內(nèi)質(zhì)網(wǎng)應(yīng)激的關(guān)系。 3.探討深低溫停循環(huán)后急性腎損傷與炎癥反應(yīng)的關(guān)系。 4.初步探索不同停循環(huán)溫度對術(shù)后腎功能的影響。 方法 28只成年雄性SD大鼠,隨機(jī)分為以下五組：A組(深低溫：15℃-20℃,n=6),B組(亞深低溫：20℃-25℃,n=6),C組(中低溫：25℃-30℃,n=6),D組(體外循環(huán),n=6),E組(對照組,n=4)。經(jīng)過麻醉、氣管插管、動靜脈穿刺置管后,A、B、C三個低溫停循環(huán)組建立體外循環(huán),經(jīng)歷降溫、全身停循環(huán)、復(fù)溫過程；體外循環(huán)D組只進(jìn)行體外循環(huán),沒有全身停循環(huán)過程；E組為對照組,僅行左股動脈穿刺后監(jiān)測血流動力學(xué),沒有體外循環(huán)過程。分別在術(shù)前(T1)、全身停循環(huán)前(T2)、復(fù)跳后(T3)、停體外循環(huán)前(T4)及處死前(T5)五個不同時間點(diǎn)動態(tài)監(jiān)測大鼠血?dú)?實(shí)驗(yàn)過程中實(shí)時監(jiān)測血流動力學(xué)指標(biāo)。脫離體外循環(huán)機(jī),繼續(xù)機(jī)械通氣1小時后處死大鼠,取腎組織及動脈血液進(jìn)行各指標(biāo)的檢測。 腎功能方面,比較了五組大鼠腎功能經(jīng)典指標(biāo)血肌酐的變化情況。病理形態(tài)方面,使用光鏡觀察不同組別腎小管的損傷情況,使用掃描電鏡觀察腎組織超微結(jié)構(gòu)(包括線粒體、內(nèi)質(zhì)網(wǎng)和細(xì)胞核)變化,使用TUNEL法檢測不同組別大鼠腎組織的凋亡情況。使用ELISA法檢測腎組織促炎因子IL-1、IL-6、TNF-a的釋放水平,使用Western Blot法檢測腎組織內(nèi)質(zhì)網(wǎng)應(yīng)激相關(guān)蛋白CHOP、GRP-78、Caspase-12、 NF-κB及凋亡相關(guān)蛋白Bax、Bcl-2、Caspase-3的表達(dá)情況,使用RealTime PCR法檢測Caspase-3、CHOP及GRP-78三個基因的mRNA水平。 結(jié)果 三個低溫停循環(huán)組的血肌酐水平顯著高于體外循環(huán)組及對照組(P0.05),三組之間無差異。促炎因子的釋放方面,三個低溫停循環(huán)組顯著高于對照組(P0.05)。光鏡觀察腎小管的損傷情況為三個低溫停循環(huán)組受損程度重于體外循環(huán)組及對照組,且停循環(huán)溫度越高,受損越重。掃描電鏡下觀察腎組織超微結(jié)構(gòu),在線粒體及內(nèi)質(zhì)網(wǎng)損傷方面,與光鏡觀察腎小管受損趨勢一致,三個低溫停循環(huán)組腎組織受損程度重于體外循環(huán)組及對照組,三組之間停循環(huán)溫度越高,受損越重。在TUNEL法檢測凋亡方面,各組腎臟凋亡細(xì)胞均很少見,為生理性凋亡。在蛋白及其基因的表達(dá)方面,CHOP蛋白及其mRNA水平各組之間具有統(tǒng)計學(xué)差異,三個低溫停循環(huán)組的CHOP蛋白及其mRNA水平均顯著高于體外循環(huán)組及對照組(P0.05),三組之間無差異。其他蛋白及mRNA的表達(dá)水平未達(dá)到統(tǒng)計學(xué)差異。 結(jié)論 1.本研究從腎功能經(jīng)典指標(biāo)血肌酐、病理形態(tài)學(xué)觀察(光鏡、掃描電鏡)、炎癥因子釋放、內(nèi)質(zhì)網(wǎng)應(yīng)激標(biāo)志性蛋白CHOP及其nRNA的表達(dá)多層次多角度證實(shí),深低溫停循環(huán)可導(dǎo)致急性腎損傷。 2.掃描電鏡下超微結(jié)構(gòu)結(jié)果表明低溫停循環(huán)組腎組織內(nèi)質(zhì)網(wǎng)受損較重,同時內(nèi)質(zhì)網(wǎng)應(yīng)激反應(yīng)的標(biāo)志蛋白CHOP在三個低溫停循環(huán)組的表達(dá)顯著高于對照組,結(jié)合以上兩個結(jié)果推測深低溫停循環(huán)術(shù)后發(fā)生的急性腎損傷可能與內(nèi)質(zhì)網(wǎng)應(yīng)激相關(guān)。 3.結(jié)合CHOP蛋白、其mRNA以及炎癥因子的表達(dá)情況,綜合近期研究結(jié)論推測CHOP可能通過調(diào)控炎性反應(yīng)參與深低溫停循環(huán)術(shù)后的急性腎損傷。 4.雖然在腎功能及內(nèi)質(zhì)網(wǎng)應(yīng)激標(biāo)志性蛋白CHOP及其mRNA的表達(dá)方面,停循環(huán)在不同溫度后發(fā)生急性腎損傷的程度無顯著差別,但在光鏡以及掃描電鏡下的病理形態(tài)學(xué)方面提示,停循環(huán)溫度越高,腎臟損傷程度越重。綜合復(fù)雜多變的臨床實(shí)際情況,建議開展深入的動物實(shí)驗(yàn)及大規(guī)模前瞻性臨床實(shí)驗(yàn),進(jìn)一步研究不同停循環(huán)溫度對術(shù)后腎功能的影響。
[Abstract]:Objective: To retrospectively analyze the clinical data of patients undergoing total aortic arch replacement under deep hypothermic circulatory arrest and explore the perioperative risk factors of acute renal injury after total aortic arch replacement.
Methods: The clinical data of patients undergoing total aortic arch replacement under deep hypothermic circulatory arrest from June 2012 to June 2013 were analyzed. The acute renal injury and its degree of injury were defined by RIFLE standard. The patients were divided into non-acute renal injury group (normal renal function group) and acute renal injury group (including risk stage, injury stage, failure stage). The incidence of acute renal injury after total aortic arch replacement under deep hypothermic circulatory arrest was calculated and the perioperative risk factors of acute renal injury were identified by logistic regression analysis.
Results: A total of 130 patients, aged 48.8 (+ 10.0) years, including 94 males (72.3%). 67 patients (51.5%) were in the stage of injury or failure after operation. A total of 17 patients (13.1%) underwent postoperative hemodialysis. Multivariate logistic regression analysis showed that the patient's age (OR = 1.055, 95% CI = 1.003-1.110, P = 0.039) was diagnosed preoperatively. Aortic dissection (OR = 21.770, 95% CI = 1.888-251.050, P = 0.014) and total perioperative red blood cell input (OR = 1.108, 95% CI =.1.002-1.225, P = 0.046) were independent risk factors for acute renal injury after aortic arch replacement.
Conclusion: The incidence of acute renal injury after total aortic arch replacement under deep hypothermic circulatory arrest is higher, and the incidence of acute renal injury after total aortic arch replacement requires clinical intervention is 51.5% (including injury and failure). Independent risk factors.
objective
1. To determine whether deep hypothermia circulatory arrest (DHCA) can cause acute kidney injury (AKI).
2. to investigate the relationship between endoplasmic reticulum stress and acute kidney injury after deep hypothermia circulatory arrest.
3. to explore the relationship between acute kidney injury and inflammatory response after deep hypothermia circulatory arrest.
4. to explore the effects of different circulatory arrest temperatures on postoperative renal function.
Method
Twenty-eight adult male SD rats were randomly divided into five groups: group A (deep hypothermia: 15-20, n = 6), group B (sub-deep hypothermia: 20-25, n = 6), group C (moderate hypothermia: 25-30, n = 6), group D (cardiopulmonary bypass, n = 6), group E (control group, n = 4). After anesthesia, tracheal intubation, arteriovenous puncture and catheterization, three hypothermic circulatory arrest groups A, B, C were used to establish stereoscopic extracorporeal circulation. Group D underwent cardiopulmonary bypass without systemic circulatory arrest, while group E underwent left femoral artery puncture without cardiopulmonary bypass. Blood gas was monitored dynamically at five different time points, and hemodynamic parameters were monitored in real time during the experiment. Rats were executed after one hour of mechanical ventilation after leaving the cardiopulmonary bypass machine.
In terms of renal function, the changes of serum creatinine, a classical index of renal function, were compared in five groups. Pathological morphology, the damage of renal tubules in different groups was observed by light microscopy, the ultrastructure of renal tissues (including mitochondria, endoplasmic reticulum and nucleus) was observed by scanning electron microscopy, and the renal tissues in different groups were detected by TUNEL method. The levels of IL-1, IL-6 and TNF-a were detected by ELISA, and the expressions of stress-related proteins CHOP, GRP-78, Caspase-12, NF-kappa B and apoptosis-related proteins Bax, Bcl-2 and Caspase-3 were detected by Western Blot. The expressions of Caspase-3, CHOP and GRP-78 genes were detected by RealTime PCR. MRNA level.
Result
The levels of serum creatinine in the three hypothermic circulatory arrest groups were significantly higher than those in the cardiopulmonary bypass group and the control group (P 0.05), but there was no difference among the three groups. The ultrastructure of renal tissue was observed under scanning electron microscope. The damage trend of renal tubules was similar to that of mitochondria and endoplasmic reticulum under light microscope. The damage degree of renal tissue in three hypothermic circulatory arrest groups was more serious than that in cardiopulmonary bypass group and control group. The expression of CHOP protein and its mRNA was significantly different among the three groups. The levels of CHOP protein and its mRNA in the three hypothermic circulatory arrest groups were significantly higher than those in the cardiopulmonary bypass group and the control group (P 0.05). The expression levels of other proteins and mRNA did not reach statistical difference.
conclusion
1. This study confirmed that deep hypothermic circulatory arrest could induce acute renal injury from the following aspects: serum creatinine, pathological morphology (light microscopy, scanning electron microscopy), release of inflammatory factors, expression of endoplasmic reticulum stress marker protein CHOP and its nRNA.
2. The results of scanning electron microscopy showed that the renal endoplasmic reticulum was damaged seriously in hypothermic circulatory arrest group, and the expression of CHOP, a marker of endoplasmic reticulum stress response, was significantly higher in the three hypothermic circulatory arrest groups than in the control group. Close.
3. Combined with the expression of CHOP protein, its mRNA and inflammatory factors, we conclude that CHOP may participate in acute renal injury after deep hypothermic circulatory arrest by regulating inflammatory response.
4. Although there was no significant difference in renal function and expression of endoplasmic reticulum stress marker protein CHOP and its mRNA in the degree of acute renal injury after circulatory arrest at different temperatures, the higher the temperature of circulatory arrest, the more severe the degree of renal injury was revealed by light microscopy and scanning electron microscopy. As a matter of fact, it is suggested to carry out in-depth animal experiments and large-scale prospective clinical trials to further study the effects of different circulatory arrest temperatures on renal function after operation.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R614
本文編號：2179299
[Abstract]:Objective: To retrospectively analyze the clinical data of patients undergoing total aortic arch replacement under deep hypothermic circulatory arrest and explore the perioperative risk factors of acute renal injury after total aortic arch replacement.
Methods: The clinical data of patients undergoing total aortic arch replacement under deep hypothermic circulatory arrest from June 2012 to June 2013 were analyzed. The acute renal injury and its degree of injury were defined by RIFLE standard. The patients were divided into non-acute renal injury group (normal renal function group) and acute renal injury group (including risk stage, injury stage, failure stage). The incidence of acute renal injury after total aortic arch replacement under deep hypothermic circulatory arrest was calculated and the perioperative risk factors of acute renal injury were identified by logistic regression analysis.
Results: A total of 130 patients, aged 48.8 (+ 10.0) years, including 94 males (72.3%). 67 patients (51.5%) were in the stage of injury or failure after operation. A total of 17 patients (13.1%) underwent postoperative hemodialysis. Multivariate logistic regression analysis showed that the patient's age (OR = 1.055, 95% CI = 1.003-1.110, P = 0.039) was diagnosed preoperatively. Aortic dissection (OR = 21.770, 95% CI = 1.888-251.050, P = 0.014) and total perioperative red blood cell input (OR = 1.108, 95% CI =.1.002-1.225, P = 0.046) were independent risk factors for acute renal injury after aortic arch replacement.
Conclusion: The incidence of acute renal injury after total aortic arch replacement under deep hypothermic circulatory arrest is higher, and the incidence of acute renal injury after total aortic arch replacement requires clinical intervention is 51.5% (including injury and failure). Independent risk factors.
objective
1. To determine whether deep hypothermia circulatory arrest (DHCA) can cause acute kidney injury (AKI).
2. to investigate the relationship between endoplasmic reticulum stress and acute kidney injury after deep hypothermia circulatory arrest.
3. to explore the relationship between acute kidney injury and inflammatory response after deep hypothermia circulatory arrest.
4. to explore the effects of different circulatory arrest temperatures on postoperative renal function.
Method
Twenty-eight adult male SD rats were randomly divided into five groups: group A (deep hypothermia: 15-20, n = 6), group B (sub-deep hypothermia: 20-25, n = 6), group C (moderate hypothermia: 25-30, n = 6), group D (cardiopulmonary bypass, n = 6), group E (control group, n = 4). After anesthesia, tracheal intubation, arteriovenous puncture and catheterization, three hypothermic circulatory arrest groups A, B, C were used to establish stereoscopic extracorporeal circulation. Group D underwent cardiopulmonary bypass without systemic circulatory arrest, while group E underwent left femoral artery puncture without cardiopulmonary bypass. Blood gas was monitored dynamically at five different time points, and hemodynamic parameters were monitored in real time during the experiment. Rats were executed after one hour of mechanical ventilation after leaving the cardiopulmonary bypass machine.
In terms of renal function, the changes of serum creatinine, a classical index of renal function, were compared in five groups. Pathological morphology, the damage of renal tubules in different groups was observed by light microscopy, the ultrastructure of renal tissues (including mitochondria, endoplasmic reticulum and nucleus) was observed by scanning electron microscopy, and the renal tissues in different groups were detected by TUNEL method. The levels of IL-1, IL-6 and TNF-a were detected by ELISA, and the expressions of stress-related proteins CHOP, GRP-78, Caspase-12, NF-kappa B and apoptosis-related proteins Bax, Bcl-2 and Caspase-3 were detected by Western Blot. The expressions of Caspase-3, CHOP and GRP-78 genes were detected by RealTime PCR. MRNA level.
Result
The levels of serum creatinine in the three hypothermic circulatory arrest groups were significantly higher than those in the cardiopulmonary bypass group and the control group (P 0.05), but there was no difference among the three groups. The ultrastructure of renal tissue was observed under scanning electron microscope. The damage trend of renal tubules was similar to that of mitochondria and endoplasmic reticulum under light microscope. The damage degree of renal tissue in three hypothermic circulatory arrest groups was more serious than that in cardiopulmonary bypass group and control group. The expression of CHOP protein and its mRNA was significantly different among the three groups. The levels of CHOP protein and its mRNA in the three hypothermic circulatory arrest groups were significantly higher than those in the cardiopulmonary bypass group and the control group (P 0.05). The expression levels of other proteins and mRNA did not reach statistical difference.
conclusion
1. This study confirmed that deep hypothermic circulatory arrest could induce acute renal injury from the following aspects: serum creatinine, pathological morphology (light microscopy, scanning electron microscopy), release of inflammatory factors, expression of endoplasmic reticulum stress marker protein CHOP and its nRNA.
2. The results of scanning electron microscopy showed that the renal endoplasmic reticulum was damaged seriously in hypothermic circulatory arrest group, and the expression of CHOP, a marker of endoplasmic reticulum stress response, was significantly higher in the three hypothermic circulatory arrest groups than in the control group. Close.
3. Combined with the expression of CHOP protein, its mRNA and inflammatory factors, we conclude that CHOP may participate in acute renal injury after deep hypothermic circulatory arrest by regulating inflammatory response.
4. Although there was no significant difference in renal function and expression of endoplasmic reticulum stress marker protein CHOP and its mRNA in the degree of acute renal injury after circulatory arrest at different temperatures, the higher the temperature of circulatory arrest, the more severe the degree of renal injury was revealed by light microscopy and scanning electron microscopy. As a matter of fact, it is suggested to carry out in-depth animal experiments and large-scale prospective clinical trials to further study the effects of different circulatory arrest temperatures on renal function after operation.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R614
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