Imberti R, Vairetti M, Gualea M R, Feletti F, Poma G, Richelmi P, Preseglio I, Bellomo G
Servizio di Anestesia e Rianimazione II, IRCCS Policlinico S. Matteo and University of Pavia, Italy.
Anesth Analg. 1998 Jun;86(6):1187-93. doi: 10.1097/00000539-199806000-00009.
We investigated the effects of thyroid hormone modulation on liver injury associated with ischemia-reperfusion (I-R) and cold storage in rats. First, euthyroid and thyroxine (T4)-pretreated rats were exposed in vivo to 20-min global liver ischemia, then 30-min reperfusion. Liver injury was assessed by measuring serum alanine aminotransferase (ALT) levels. Liver concentrations of adenine nucleotides, reduced glutathione (GSH), and oxidized glutathione were evaluated. Second, rats were given the antithyroid drug propylthiouracil (PTU). Livers stored at 0-1 degrees C in Euro-Collins' solution for 20 h were reperfused at 37 degrees C for 15 min. Lactate dehydrogenase (LDH) in the effluent perfusate and bile flow were evaluated during reperfusion. Serum ALT levels increased after ischemia and I-R. ALT increased significantly more in T4-pretreated than in euthyroid rats after ischemia and I-R. Preischemic levels of adenosine triphosphate (ATP) were significantly lower in livers from T4-pretreated than in euthyroid rats (6.22 +/- 0.7 and 11 +/- 0.9 nmol/mg protein, respectively; P < 0.05). After ischemia, liver ATP was similarly reduced in T4-pretreated and euthyroid rats. After reperfusion, ATP partially recovered in euthyroid rats but remained low in T4-pretreated rats (6.7 +/- 1.0 and 1.91 +/- 0.7 nmol/mg protein, respectively; P < 0.05). Preischemic levels of liver GSH decreased to 44% in T4-pretreated rats. After ischemia, GSH decreased similarly in euthyroid and T4-pretreated rats. GSH recovered promptly after reperfusion in euthyroid rats but remained low in T4-pretreated rats (13.9 +/- 3.3 and 3.9 +/- 0.9 nmol/mg protein, respectively; P < 0.02). During reperfusion after cold storage, LDH in effluent perfusate was significantly lower and bile flow higher in livers from PTU-pretreated rats than from euthyroid rats. The histopathological changes observed after I-R and cold storage confirmed the biochemical findings. Our results suggest that T4 administration exacerbates pretransplant liver damage by increasing liver susceptibility to I-R, whereas PTU administration reduces the liver injury associated with cold storage.
We studied the effects of thyroid hormone modulation on liver injury associated with ischemia-reperfusion and cold storage in rats. Thyroxine administration increased susceptibility to ischemia-reperfusion injury, whereas the antithyroid agent propylthiouracil reduced the deleterious effects associated with cold storage.
我们研究了甲状腺激素调节对大鼠缺血再灌注（I-R）及冷藏相关肝损伤的影响。首先，将甲状腺功能正常和经甲状腺素（T4）预处理的大鼠在体内进行20分钟的全肝缺血，然后再灌注30分钟。通过测量血清丙氨酸转氨酶（ALT）水平评估肝损伤。评估肝中腺嘌呤核苷酸、还原型谷胱甘肽（GSH）和氧化型谷胱甘肽的浓度。其次，给大鼠服用抗甲状腺药物丙硫氧嘧啶（PTU）。将在Euro-Collins溶液中于0-1℃储存20小时的肝脏在37℃再灌注15分钟。在再灌注期间评估流出灌注液中的乳酸脱氢酶（LDH）和胆汁流量。缺血及I-R后血清ALT水平升高。缺血及I-R后，T4预处理的大鼠中ALT升高明显高于甲状腺功能正常的大鼠。T4预处理大鼠肝脏中的缺血前三磷酸腺苷（ATP）水平显著低于甲状腺功能正常的大鼠（分别为6.22±0.7和11±0.9 nmol/mg蛋白；P<0.05）。缺血后，T4预处理和甲状腺功能正常的大鼠肝脏中的ATP同样减少。再灌注后，甲状腺功能正常的大鼠中ATP部分恢复，但T4预处理的大鼠中仍保持低水平（分别为6.7±1.0和1.91±0.7 nmol/mg蛋白；P<0.05）。T4预处理大鼠肝脏的缺血前GSH水平降至44%。缺血后，甲状腺功能正常和T4预处理的大鼠中GSH同样减少。甲状腺功能正常的大鼠再灌注后GSH迅速恢复，但T4预处理的大鼠中仍保持低水平（分别为13.9±3.3和3.9±0.9 nmol/mg蛋白；P<0.02）。在冷藏后的再灌注期间，PTU预处理大鼠肝脏流出灌注液中的LDH显著低于甲状腺功能正常的大鼠，胆汁流量则更高。I-R及冷藏后观察到的组织病理学变化证实了生化结果。我们的结果表明，给予T4会增加肝脏对I-R的易感性，从而加剧移植前肝损伤，而给予PTU可减轻与冷藏相关的肝损伤。
我们研究了甲状腺激素调节对大鼠缺血再灌注及冷藏相关肝损伤的影响。给予甲状腺素增加了对缺血再灌注损伤的易感性，而抗甲状腺药物丙硫氧嘧啶减轻了与冷藏相关的有害影响。
