Ueda T, Ho H S, Anderson S E, Takeyama Y
Department of Surgery, University of California Davis School of Medicine, Davis, California, 95616, USA.
J Surg Res. 1999 Apr;82(2):305-11. doi: 10.1006/jsre.1998.5539.
Multiple organ failure (MOF) is the most serious complication in severe acute pancreatitis, contributing to its high mortality. It has been suggested that changes of high-energy phosphates, intracellular pH, and intracellular cation homeostasis are closely related to hepatocellular injury associated with MOF.
Phosphorus metabolites, intracellular pH (pHi), and intracellular Na+ concentration ([Na+]i) were measured in rat livers in vivo using 31P and 23Na NMR spectroscopy after deoxycholic acid (DCA)-induced pancreatitis or intraperitoneal injection (ip) of pancreatitis-induced ascitic fluid (PAF).
Two hours after induction of DCA-pancreatitis, the liver experienced significant intracellular acidosis (pHi = 6.99 +/- 0.16) and sodium loading (75 +/- 9 mM) and a reduction in its energy state (beta-ATP/Pi = 0.2 +/- 0.03 and Pi = 164 +/- 12). Although ip injection of PAF into healthy rats did not induce systemic hypotension, the livers under these conditions also developed severe disturbances in hepatocellular ion homeostasis and depletion of its bioenergetics. The longer the abdomen was exposed to the PAF, the worse the changes were. At 3 h after ip injection of PAF, hepatic [Na+]i significantly increased (42 +/- 3 mM) along with a significant decrease in pHi (7.30 +/- 0. 03). At 6 h after ip injection of PAF, the hepatic beta-ATP/Pi ratio decreased to 0.34 +/- 0.05 and Pi increased to 97 +/- 27.
PAF induced severe hepatocellular acidosis, rapid accumulation of hepatic intracellular sodium, impaired hepatic cytosolic phosphorylation potential, and increased hepatic utilization of ATP. These effects may account for the eventual development of liver dysfunction associated with necrotizing pancreatitis.
多器官功能衰竭（MOF）是重症急性胰腺炎最严重的并发症，导致其死亡率很高。有人提出，高能磷酸盐、细胞内pH值和细胞内阳离子稳态的变化与MOF相关的肝细胞损伤密切相关。
在脱氧胆酸（DCA）诱导的胰腺炎或腹腔注射（ip）胰腺炎诱导的腹水（PAF）后，使用31P和23Na核磁共振波谱法在大鼠体内测量肝脏中的磷代谢物、细胞内pH值（pHi）和细胞内Na+浓度（[Na+]i）。
DCA诱导胰腺炎两小时后，肝脏出现明显的细胞内酸中毒（pHi = 6.99 ± 0.16）和钠负荷增加（75 ± 9 mM），其能量状态降低（β-ATP/Pi = 0.2 ± 0.03，Pi = 164 ± 12）。虽然向健康大鼠腹腔注射PAF未诱发全身性低血压，但在这些条件下肝脏也出现了严重的肝细胞离子稳态紊乱及其生物能消耗。腹部暴露于PAF的时间越长，变化越严重。腹腔注射PAF后3小时，肝脏[Na+]i显著增加（42 ± 3 mM），同时pHi显著降低（7.30 ± 0.03）。腹腔注射PAF后6小时，肝脏β-ATP/Pi比值降至0.34 ± 0.05，Pi升至97 ± 27。
PAF诱导严重的肝细胞酸中毒、肝细胞内钠快速积累、肝细胞质磷酸化电位受损以及肝脏ATP利用增加。这些作用可能解释了与坏死性胰腺炎相关的肝功能障碍的最终发展。
