Yilmaz S, Koken T, Tokyol C, Kahraman A, Akbulut G, Serteser M, Polat C, Gokce C, Gokce O
Department of General Surgery, Faculty of Medicine, Afyon Kocatepe University, Afyon, Turkey.
Surg Endosc. 2003 May;17(5):819-24. doi: 10.1007/s00464-002-9096-z. Epub 2003 Jan 18.
Pneumoperitoneum (P) created to facilitate laparoscopy (L) is associated with splanchnic perfusion, ischemia/reperfusion (I/R) injury, and oxidative stress. In this randomized controlled experimental study with blind outcome assessment, we evaluated the effect of preconditioning (PRE) on L-induced I/R injury.
The subjects were 40 Sprague-Dawley male rats. P was created in all except controls, using carbondioxide (CO2) insufflation under a pressure of 15 mmHg. PRE consisted of 10 min of P, followed by 10 min of deflation (D). The rats were randomized to the following groups: Group P was subjected to 60 min of P. Group P/D was subjected to 60 min of P, followed by 45 min of D. Group PRE/P was subjected to PRE, followed by 60 min of P. Group PRE/P/D was subjected to PRE, followed by 60 min of P and 45 min of D. Group C (control) was subjected to a sham operation, without P. Its anesthesia time was equal to that for group PRE/P/D. At the end of the experiments, the rats were killed; blood, liver, and kidney samples were then obtained and coded. Plasma alanine aminotransferase (ALT) and malondialdehyde (MDA), as well as homogenized tissue MDA levels and glutathione (GSH) activities, were measured; tissue samples were assessed for histopathological evidence of injury; all assessments were done by investigators blinded to the study design. The results were decoded and analyzed statistically with the Kruskal-Wallis and Mann Whitney tests. A p <0.05 was considered significant.
Plasma ALT as well as plasma, liver, and kidney MDA levels and liver and kidney injury scores were increased, whereas liver and kidney GSH values were decreased in groups P and P/D, as compared to group C. Rats subjected to PRE before P had plasma ALT, kidney MDA, and kidney and liver GSH levels comparable to controls; their kidney and liver injury scores were higher than controls but significantly lower than nonpreconditioned animals. PRE enabled decreased plasma, kidney, and liver MDA as well as increased kidney GSH if applied before P; its efficacy on oxidative stress was limited to providing decreased kidney MDA and increased kidney GSH if applied before P/D. However, PRE significantly attenuated kidney and liver injury after P as well as P/D.
PRE consisting of 10 min of P followed by 10 min of D decreases the oxidative stress induced by sustained P in the plasma, liver, and kidney. PRE significantly limits liver and kidney injury after prolonged P and P/D. After further studies to define its ideal timing, PRE before L incorporating P may have clinical relevance, especially for elderly patients or those with impaired hepatic and/or renal function or perfusion.
为便于进行腹腔镜检查（L）而建立的气腹（P）与内脏灌注、缺血/再灌注（I/R）损伤及氧化应激相关。在这项采用盲法结果评估的随机对照实验研究中，我们评估了预处理（PRE）对L诱导的I/R损伤的影响。
实验对象为40只雄性Sprague-Dawley大鼠。除对照组外，其余大鼠均通过在15 mmHg压力下注入二氧化碳（CO₂）建立气腹。预处理包括10分钟气腹，随后10分钟放气（D）。大鼠被随机分为以下几组：P组接受60分钟气腹；P/D组接受60分钟气腹，随后45分钟放气；PRE/P组先进行预处理，随后接受60分钟气腹；PRE/P/D组先进行预处理，随后接受60分钟气腹和45分钟放气；C组（对照组）接受假手术，不建立气腹。其麻醉时间与PRE/P/D组相同。实验结束时，处死大鼠；采集血液、肝脏和肾脏样本并编码。检测血浆丙氨酸转氨酶（ALT）和丙二醛（MDA）以及组织匀浆MDA水平和谷胱甘肽（GSH）活性；评估组织样本的损伤组织病理学证据；所有评估均由对研究设计不知情的研究人员进行。对结果进行解码，并采用Kruskal-Wallis检验和Mann-Whitney检验进行统计学分析。p<0.05被认为具有统计学意义。
与C组相比，P组和P/D组的血浆ALT、血浆、肝脏和肾脏MDA水平以及肝脏和肾脏损伤评分升高，而肝脏和肾脏GSH值降低。在气腹前进行预处理的大鼠，其血浆ALT、肾脏MDA以及肾脏和肝脏GSH水平与对照组相当；其肾脏和肝脏损伤评分高于对照组，但显著低于未预处理的动物。如果在气腹前应用预处理，可降低血浆、肾脏和肝脏MDA水平，并增加肾脏GSH水平；如果在气腹/放气前应用预处理，其对氧化应激的作用仅限于降低肾脏MDA水平和增加肾脏GSH水平。然而，预处理可显著减轻气腹以及气腹/放气后的肾脏和肝脏损伤。
由10分钟气腹随后10分钟放气组成的预处理可降低血浆、肝脏和肾脏中持续气腹诱导的氧化应激。预处理可显著减轻长时间气腹和气腹/放气后的肝脏和肾脏损伤。在进一步研究确定其理想时机后，在包含气腹的腹腔镜检查前进行预处理可能具有临床意义，尤其对于老年患者或肝肾功能或灌注受损的患者。
