Hanly Eric J, Aurora Alexander A, Shih Samuel P, Fuentes Joseph M, Marohn Michael R, De Maio Antonio, Talamini Mark A
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Surgery. 2007 Sep;142(3):357-64. doi: 10.1016/j.surg.2007.02.017.
We have shown previously that abdominal insufflation with CO(2) increases serum levels of IL-10 and TNFalpha and increases survival among animals with lipopolysaccharide (LPS)-induced sepsis, even after a laparotomy. We demonstrated previously that the effect of CO(2) is not from changes in systemic pH, although the peritoneum is locally acidotic during abdominal insufflation with CO(2) even when systemic pH is corrected. We hypothesized that acidification of the peritoneum via means other than CO(2) insufflation would produce alterations in the inflammatory response similar to those associated with CO(2) pneumoperitoneum.
In total, 42 rats were randomized into 7 groups (n = 6): 1) LPS only, 2) anesthesia control, 3) helium pneumoperitoneum, 4) CO(2) pneumoperitoneum, 5) buffered mild acid lavage, 6) buffered strong acid lavage, and 7) buffered strong acid lavage + helium pneumoperitoneum. Animals received anesthesia with vaporized isoflurane (except the LPS-only group) and their respective abdominal treatment (pneumoperitoneum and/or lavage) for 30 min followed immediately by stimulation with systemic LPS (1 mg/kg, IV). Blood was harvested via cardiac puncture 60 min after LPS injection, and serum levels of IL-10 and TNFalpha levels were determined by enzyme-linked immunosorbent assay.
Mean peritoneal pH decreased (P < .05) after CO(2) pneumoperitoneum, buffered strong acid lavage, and buffered strong acid lavage + helium pneumoperitoneum, and it decreased (P = .1) after helium pneumoperitoneum alone and buffered mild acid lavage. IL-10 levels were increased (P < .01), and TNFalpha levels decreased (P < .001) among animals with acidic peritoneal cavities compared with animals with pH-normal peritoneal cavities. Decreasing peritoneal pH correlated with both increasing IL-10 levels (r = -.465, P < .01) and decreasing TNFalpha levels (r = 0.448, P < .01). Among animals with peritoneal acidosis, there were no differences in levels of IL-10 or TNFalpha regardless of insufflation status (P > .05 for both cytokines).
Acidification of the peritoneal cavity whether by abdominal insufflation or by peritoneal acid lavage increases serum IL-10 and decreases serum TNFalpha levels in response to systemic LPS challenge. The degree of peritoneal acidification correlates with the degree of inflammatory response reduction. These results support the hypothesis that pneumoperitoneum-mediated attenuation of the inflammatory response after laparoscopic surgery occurs via a mechanism of peritoneal cell acidification.
我们之前已经表明,即使在剖腹手术后,用二氧化碳进行腹腔充气也会增加血清白细胞介素-10(IL-10)和肿瘤坏死因子α(TNFα)水平,并提高脂多糖(LPS)诱导的脓毒症动物的存活率。我们之前证明,二氧化碳的作用并非源于全身pH值的变化,尽管在二氧化碳腹腔充气期间,即使全身pH值得到纠正,腹膜局部仍呈酸中毒状态。我们推测,通过二氧化碳充气以外的方式使腹膜酸化会产生与二氧化碳气腹相关的类似炎症反应改变。
总共42只大鼠被随机分为7组(每组n = 6):1)仅LPS组,2)麻醉对照组,3)氦气气腹组,4)二氧化碳气腹组,5)缓冲弱酸灌洗组,6)缓冲强酸灌洗组,7)缓冲强酸灌洗 + 氦气气腹组。动物用挥发的异氟烷进行麻醉(仅LPS组除外),并接受各自的腹部处理(气腹和/或灌洗)30分钟,随后立即静脉注射全身LPS(1 mg/kg)进行刺激。在LPS注射后60分钟通过心脏穿刺采集血液,通过酶联免疫吸附测定法测定血清IL-10和TNFα水平。
二氧化碳气腹、缓冲强酸灌洗以及缓冲强酸灌洗 + 氦气气腹后平均腹膜pH值降低(P < 0.05),单独氦气气腹和缓冲弱酸灌洗后腹膜pH值也降低(P = 0.1)。与腹膜pH值正常的动物相比,腹膜腔呈酸性的动物中IL-10水平升高(P < 0.01),TNFα水平降低(P < 0.001)。腹膜pH值降低与IL-10水平升高(r = -0.465,P < 0.01)和TNFα水平降低(r = 0.448,P < 0.01)均相关。在腹膜酸中毒的动物中,无论充气状态如何,IL-10或TNFα水平均无差异(两种细胞因子P均 > 0.05)。
无论是通过腹腔充气还是通过腹膜酸灌洗使腹膜腔酸化,在全身LPS刺激后都会增加血清IL-10并降低血清TNFα水平。腹膜酸化程度与炎症反应减轻程度相关。这些结果支持以下假设:腹腔镜手术后气腹介导的炎症反应减弱是通过腹膜细胞酸化机制发生的。