维持基线心输出量和血压治疗腹腔高压致急性肾损伤的实验研究

Renal Protective Effect and Its Related Mechanisms of Elevated Cardiac Output and Blood Pressure to Baseline Treatments in Acute Kidney Injury Model Caused by Intra-abdominal Hypertension

目的:对腹腔高压(IAH)致急性肾损伤模型,采用强心药物维持血压至基线水平,以改善肾脏灌注,探讨其保护和治疗作用。方法:将12只健康小香猪,随机分为两组各6只,均在全麻后收集单位时间的尿量,使用Pi CCO连续监测血流动力学数据和激光多普勒血流灌注成像仪监测肾脏表面血流;采用二氧化碳气腹法建立IAH模型,连续监测腹腔内压(IAP),获得MAP、IAP和APP。两组动物IAP均从基线逐步升高至10 mmHg、15 mmHg、20 mmHg和25 mmHg,然后在25 mmHg水平维持8 h后处死动物行肾组织病理学检查。基线血压组(BBP组)动物在IAP 25 mmHg维持15分钟后通过静脉泵入多巴酚丁胺提高心输出量,提高血压,维持血压于基线水平,对照组无干预,监测两组动物肾脏表面灌注、血Cr、TNF-α、IL-6和尿IL-18随IAP的变化状况。结果:随着IAP的升高,两组动物肾脏表面血流均显著下降(P<0.05);对照组血Cr和尿IL-18在IAP 25 mmHg维持8 h后显著升高(P<0.05),尿量明显减少,可以诊断AKI,血清TNF-α、IL-6明显升高(P<0.05)。BBP组提高心输出量和血压治疗后,肾脏表面灌注显著改善(P<0.05),血Cr及尿IL-18较对照组明显下降(P<0.05),尿量明显增加(P<0.05),而血TNF-α、IL-6较对照组无显著差异(P>0.05)。多组肾脏病理学检查均表现为肾小球肿胀和肾小管水肿,差异不明显。结论:在IAH 25 mmHg维持8 h能造成急性肾损伤模型,采用多巴酚丁胺方法可以明显提高心输出量和血压,进而改善肾脏表面灌注,发挥肾保护作用。

Objective:To evaluate the renal protective effect of elevated cardiac and blood pressure to baseline treatment in intra-abdominal hypertension(IAH)and further investigate its related mechanisms.Methods:12 healthy pigs were randomly divided into experimental and control group,each had 6 pigs.All animals were collected urine volume per hour,continuously monitored mean arterial pressure(MAP)and renal cortical blood flow after anesthesia.IAH models were established by intraperitoneally injecting carbon dioxide in all animals,the baseline MAP,intra-abdominal pressure(IAP)and APP were obtained before IAH models established.In both groups,IAP was raised gradually from baseline to 10 mmHg,15 mmHg,20 mmHg and 25 mmHg.In control group,IAP was maintained at 25 mmHg for 8 hours without any other interventions.In experimental group,the animals were intravenously given with dobutamine in order to maintain cardiac output and MAP equal to its baseline values after 15 minutes of the onset of 25 mmHg IAP.Changes of renal cortical blood flow,serum creatinine,TNF-α,IL-6 and urine IL-18 with the alteration of IAP in both groups were explored.Animals were then sacrificed for renal histopathology after 8 hours of the onset of 25 mmHg IAP.Results:With the increase of IAP,renal cortical blood flow in both groups were significantly decreased(P<0.05).Compared to its baseline,serum Cr and urinary IL-18 were significantly up-regulated after the maintenance of IAP at 25 mmHg for 8 hours in control group(P<0.05).And,the level of serum TNF-αand IL-6 also changed significantly(P>0.05).In BBP group,which utilized a strategy of elevated cardiac output and blood pressure to baseline level,significant improvement of the renal cortical blood flow was observed(P<0.05).Serum Cr and urinary IL-18 were significantly decreased,but TNF-α,IL-6 did not changed significantly(P>0.05).Renal histopathological examination illustrated edema of glomerulus and tubules in three groups.Conclusions:Maintaining IAP of 25 mmHg for 8 hours can successfully make the model of AKI.The elevated cardiac output and blood pressure to baseline may have a renal protective function within the first 8 hours of IAH by improving renal cortical blood flow.