体外循环后大鼠肝损伤的研究

Hepatic injury after cardiopulmonary bypass in rats

目的：研究体外循环（CPB）对大鼠肝脏的损伤，并探讨其可能机制。方法：选用成年SD大鼠24只，随机分为伪手术组（Sham组）和CPB组。Sham组行类似操作，但不实施CPB。CPB组建立CPB，最大流量≥100mV（kg·min）转流60min。于肝素化后转流前（T1）和转流结束后（T2）进行动脉血气分析。测T1、1、2、术后30min（T3）、术后1h（T4）、术后2h（T5）、术后3h（T6）以及术后24h（T7）的ALT、AST和LDH以及TNF-α术后24h取肝组织，测定丙二醛（MDA）、总一氧化氮合酶（tNOS）、诱导型一氧化氮合酶（iNOS）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、还原性谷胱甘肽（GSH）、谷胱甘肽还原酶（GSSG—R）、谷胱甘肽巯基转移酶（GST）和谷胱甘肽过氧化物酶（GSH-Px），同时行组织学检查。结果：CPB后大鼠血压、红细胞压积（HCT）、动脉血氧分压PaO2和PH值较Sham组有统计学改变，但仍在可接受范围。CPB组大鼠术后肝功能指标较Sham组均有显著的升高，峰值出现在术后1～2h。血清TNF-α也呈现明显高于Sham组的趋势，同时CPB组肝MDA浓度，tNOS和iNOS活性也有较大幅度上升，而GSH浓度，SOD、CAT、GSSG—R、GST、GSH—Px活性的变化则相反。24h肝组织学检查提示心肺转流对肝造成的损伤主要表现为肝细胞坏死，炎性细胞浸润。结论：CPB对肝有损伤作用，在这一病理生理过程、炎症反应和缺血再灌注损伤都起着举足轻重的作用，这两种机制相互影响、相互诱导、相互促进，最终导致了严重的肝损伤。

Objective： To investigate the influence of cardiopulmonary bypass （CPB） on liver in rats and its possible mechanism. Methods： Twenty-four male Sprague-Dawley rats were equally randomized into a sham operation and a CPB group. The flow-rate was maintained at ≥ 100ml/kg/min for 60 minutes. Blood samples were collected at the beginning and the end of CPB, and 30 rain, 1 h, 2 h, 3 h and 24 h after CPB for assays of ALT, AST and LDH. Liver samples were obtained 24 h after the operation for the determination of MDA, tNOS, iNOS, GSH, SOD, CAT, GSSG-R, GST and GSH-Px. Results ： Statistically significant differences were observed in the mean arterial pressure （ MAP）, hematocrit （HCT）, oxygen tension （PaO2 ） and PH between the two groups after the operation, but all the changes were within the acceptable range. Compared with the sham operation group, the CPB group showed an obvious increase in plasma AST, ALT, LDH, TNF-α liver tNOS, iNOS and MDA and a marked decrease in the activities of SOD, CAT, GSSG-R, GSH-Px and GST and the concentration of GSH after the operation. Conclusion ： CPB evidently injures the liver in rats through increasing biomolecules, reducing antioxidants and inducing the expression of TNF-α.