Shimono Hiroo, Goromaru Teruko, Kadota Yoshitami, Tsurumaru Takeshi, Kanmura Yuichi
Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, Kagoshima, Japan.
Anesth Analg. 2003 Aug;97(2):442-448. doi: 10.1213/01.ANE.0000067407.25527.B7.
Using precision-cut liver slices (20-25 mg wet weight) from male Wistar rats, we examined whether clinically relevant propofol concentrations have hepatoprotective or -toxic effects during hypoxia/reoxygenation. Slices were preincubated for 2 h in sealed roller vials (three slices per vial) containing Waymouth's medium (37 degrees C; 95% oxygen/5% CO(2)). Then, propofol or Intralipid was added to create four different groups (control, Intralipid, small-concentration propofol [0.5-1.5 micro g/mL], and large-concentration propofol [2.0-6.0 micro g/mL]). Thereafter, each group was incubated for 4 h under 95% oxygen/5% CO(2) (no hypoxia) or for 2 h under 100% nitrogen plus 2 h under 95% oxygen/5% CO(2) (hypoxia/reoxygenation). Slice viability and hypoxia/reoxygenation injury were assessed at 2, 3, and 4 h after incubation began by using the slice intracellular K(+) concentration, energy status (adenosine triphosphate content, total adenine nucleotides content, and energy charge), and liver enzyme leakage (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase). Propofol and Intralipid caused a significant delay in energy charge recovery in comparison with the control. There were no significant differences between the propofol groups and the other two groups in intracellular K(+) content or liver enzyme leakage. Propofol had no hepatotoxic effect under no-hypoxia conditions in rat liver slices, nor did it have a protective effect against hypoxia/reoxygenation-induced hepatic injury.
Propofol had no hepatotoxic effect under no-hypoxia conditions in rat liver slices, nor did it have a protective effect against hypoxia/reoxygenation-induced hepatic injury.
我们使用雄性Wistar大鼠的精密肝切片(湿重20 - 25毫克),研究了临床相关浓度的丙泊酚在缺氧/复氧过程中是否具有肝保护或肝毒性作用。切片在密封的滚瓶(每个瓶子三片)中于含有Waymouth培养基(37摄氏度;95%氧气/5%二氧化碳)的环境中预孵育2小时。然后,加入丙泊酚或脂质乳剂以创建四个不同组(对照组、脂质乳剂组、低浓度丙泊酚组[0.5 - 1.5微克/毫升]和高浓度丙泊酚组[2.0 - 6.0微克/毫升])。此后,每组在95%氧气/5%二氧化碳(无缺氧)条件下孵育4小时,或在100%氮气条件下孵育2小时后再在95%氧气/5%二氧化碳(缺氧/复氧)条件下孵育2小时。在孵育开始后2小时、3小时和4小时,通过测量切片细胞内钾离子浓度、能量状态(三磷酸腺苷含量、总腺嘌呤核苷酸含量和能荷)以及肝酶泄漏(天冬氨酸转氨酶、丙氨酸转氨酶和乳酸脱氢酶)来评估切片活力和缺氧/复氧损伤。与对照组相比,丙泊酚和脂质乳剂导致能荷恢复显著延迟。丙泊酚组与其他两组在细胞内钾离子含量或肝酶泄漏方面无显著差异。在大鼠肝切片无缺氧条件下,丙泊酚无肝毒性作用,对缺氧/复氧诱导的肝损伤也无保护作用。
在大鼠肝切片无缺氧条件下,丙泊酚无肝毒性作用,对缺氧/复氧诱导的肝损伤也无保护作用。