单磷酸类脂A预处理对大鼠肝缺血再灌注损伤的保护作用及其机制

目的研究单磷酸类脂A（MPLA）是否通过血红素氧合酶-1-一氧化碳-环磷酸鸟苷（HO-1-CO-cGMP）途径促进降钙素基因相关肽（CGRP）释放，发挥其对大鼠肝缺血再灌注损伤的保护作用。方法健康雄性SD大鼠分为对照组、假手术组、肝脏缺血再灌注组、MPLA低、中、高剂量组（肝脏缺血再灌注＋MPLA0．2、0．5、1．0mg／kg），复制肝缺血再灌注模型，随后电子显微镜观察细胞超微结构；多功能生化分析仪测定血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、乳酸脱氢酶（LDH）和肝组织CO水平；免疫组化检测肝组织HO-1表达；放射免疫分析法测定肝组织CGRP、cGMP浓度。结果和缺血再灌注组比较，MPLA低、中、高剂量组细胞损害相对较轻；各项肝功能指标显著降低；HO-1、CO、cGMP、CGRP含量升高（P〈0．05），且HO—1与CO、CO与cGMP、cGMP与CGRP两两者之间存在明显的正相关关系（P〈0．05）。结论MPLA通过HO—1—CO-cGMP途径促进肝脏缺血／再灌注期间CGRP的合成和释放，这可能是MPLA减轻大鼠肝缺血再灌注损伤作用机制之一。

The protective effect of MPLA preconditioning on hepatic ischemia-reperfusion injury in rats and its mechanism

Objective To study the mechanism of monophosphoryl lipid A (MPLA) protecting liver ischemia-reperfusion injury in rats, and explore the hemeoxygenase-1-carbon monoxide-cyclic guanosine monophosphate (HO-1-CO-cGMP) pathway whether involved in MPLA enhance calcitonin gene-related peptides (CGRP) releasing or not. Methods Male SD rats were randomly divided into control group, sham-operated group, hepatic ischemia-reperfusion group, MPLA low, medium and high dose groups (hepatic ischemia-reperfusion + MPLA0. 2,0. 5,1.0 mg/ kg). Hepatic isehemia-reperfusion model was constructed, followed by observation of cell ultrastructure through electron microscope. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and liver tissue levels of CO were determined. HO-1 expression in liver tissue was detected by immunohistochemic, CGRP, eGMP concentration in liver tissue was detected by RIA assay. Results Compared with hepatic isehemia-reperfusion group, the cell damage in MPLA group were relatively minor, and ALT, AST, LDH were significantly decreased (P <0.05), while HO-1, CO, cGMP, CGRP levels were signifi-cantly increased (P < 0.05). HO-1 and CO, CO and cGMP, cGMP and CGRP were obviously positive correlated (P <0.05). Conclu-sion MPLA enhanced CGRP synthesis and release through HO-1-CO-cGMP pathway in liver ischemia / reperfusion, which may be one of the mechanisms of MPLA reducing hepatic ischemia-reperfusion injury in rat.