深低温停循环后急性肾损伤的危险因素和机制初探
发布时间：2018-08-12 14:11
【摘要】：目的：回顾性分析深低温停循环下行全主动脉弓置换术患者的临床资料,探索全主动脉弓置换术后急性肾损伤的围术期危险因素。 方法：通过分析我院2012年6月至2013年6月期间,深低温停循环下行全主动脉弓置换术患者的临床数据,使用RIFLE标准定义急性肾损伤及其损伤程度,将患者分为非急性肾损伤组(肾功能正常组)和急性肾损伤组(包括风险期、损伤期、衰竭期),比较两组患者围术期各项临床指标,计算患者深低温停循环下全主动脉弓置换术后急性肾损伤的发生率,并通过Logistic回归分析找出急性肾损伤的围术期危险因素。 结果：共入选130例患者,年龄(48.8±10.0)岁,其中男性94例(72.3%)。术后有67例(51.5%)的患者处于损伤期或衰竭期,其中共17例(13.1%)患者行术后血液透析治疗。多因素Logistic回归分析结果显示：患者年龄(OR=1.055,95%CI=1.003-1.110,P=0.039)、术前诊断为主动脉夹层(OR=21.770,95%CI=1.888-251.050, P=0.014)及围术期红细胞输入总量(OR=1.108,95%CI=.1.002-1.225, P=0.046)是全主动脉弓置换术后发生急性肾损伤的独立危险因素。 结论：深低温停循环下行全主动脉弓置换术后急性肾损伤的发生率较高,其中需要临床干预的发生率为51.5%(包括损伤期和衰竭期)。患者年龄、术前诊断为主动脉夹层及围术期红细胞输入总量是全主动脉弓置换术后发生急性肾损伤的独立危险因素。 目的 1.明确深低温停循环(DHCA, deep hypothermia circulatory arrest)是否可导致急性肾损伤(AKI, acute kidney injury)。 2.探讨深低温停循环后急性肾损伤与内质网应激的关系。 3.探讨深低温停循环后急性肾损伤与炎症反应的关系。 4.初步探索不同停循环温度对术后肾功能的影响。 方法 28只成年雄性SD大鼠,随机分为以下五组：A组(深低温：15℃-20℃,n=6),B组(亚深低温：20℃-25℃,n=6),C组(中低温：25℃-30℃,n=6),D组(体外循环,n=6),E组(对照组,n=4)。经过麻醉、气管插管、动静脉穿刺置管后,A、B、C三个低温停循环组建立体外循环,经历降温、全身停循环、复温过程；体外循环D组只进行体外循环,没有全身停循环过程；E组为对照组,仅行左股动脉穿刺后监测血流动力学,没有体外循环过程。分别在术前(T1)、全身停循环前(T2)、复跳后(T3)、停体外循环前(T4)及处死前(T5)五个不同时间点动态监测大鼠血气,实验过程中实时监测血流动力学指标。脱离体外循环机,继续机械通气1小时后处死大鼠,取肾组织及动脉血液进行各指标的检测。 肾功能方面,比较了五组大鼠肾功能经典指标血肌酐的变化情况。病理形态方面,使用光镜观察不同组别肾小管的损伤情况,使用扫描电镜观察肾组织超微结构(包括线粒体、内质网和细胞核)变化,使用TUNEL法检测不同组别大鼠肾组织的凋亡情况。使用ELISA法检测肾组织促炎因子IL-1、IL-6、TNF-a的释放水平,使用Western Blot法检测肾组织内质网应激相关蛋白CHOP、GRP-78、Caspase-12、 NF-κB及凋亡相关蛋白Bax、Bcl-2、Caspase-3的表达情况,使用RealTime PCR法检测Caspase-3、CHOP及GRP-78三个基因的mRNA水平。 结果 三个低温停循环组的血肌酐水平显著高于体外循环组及对照组(P0.05),三组之间无差异。促炎因子的释放方面,三个低温停循环组显著高于对照组(P0.05)。光镜观察肾小管的损伤情况为三个低温停循环组受损程度重于体外循环组及对照组,且停循环温度越高,受损越重。扫描电镜下观察肾组织超微结构,在线粒体及内质网损伤方面,与光镜观察肾小管受损趋势一致,三个低温停循环组肾组织受损程度重于体外循环组及对照组,三组之间停循环温度越高,受损越重。在TUNEL法检测凋亡方面,各组肾脏凋亡细胞均很少见,为生理性凋亡。在蛋白及其基因的表达方面,CHOP蛋白及其mRNA水平各组之间具有统计学差异,三个低温停循环组的CHOP蛋白及其mRNA水平均显著高于体外循环组及对照组(P0.05),三组之间无差异。其他蛋白及mRNA的表达水平未达到统计学差异。 结论 1.本研究从肾功能经典指标血肌酐、病理形态学观察(光镜、扫描电镜)、炎症因子释放、内质网应激标志性蛋白CHOP及其nRNA的表达多层次多角度证实,深低温停循环可导致急性肾损伤。 2.扫描电镜下超微结构结果表明低温停循环组肾组织内质网受损较重,同时内质网应激反应的标志蛋白CHOP在三个低温停循环组的表达显著高于对照组,结合以上两个结果推测深低温停循环术后发生的急性肾损伤可能与内质网应激相关。 3.结合CHOP蛋白、其mRNA以及炎症因子的表达情况,综合近期研究结论推测CHOP可能通过调控炎性反应参与深低温停循环术后的急性肾损伤。 4.虽然在肾功能及内质网应激标志性蛋白CHOP及其mRNA的表达方面,停循环在不同温度后发生急性肾损伤的程度无显著差别,但在光镜以及扫描电镜下的病理形态学方面提示,停循环温度越高,肾脏损伤程度越重。综合复杂多变的临床实际情况,建议开展深入的动物实验及大规模前瞻性临床实验,进一步研究不同停循环温度对术后肾功能的影响。
[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.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R614
本文编号：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.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R614
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