Oren R, Dotan I, Papa M, Marravi Y, Aeed H, Barg J, Zeidel L, Bruck R, Halpern Z
Department of Gastroenterology, Ichilov Hospital, Tel Aviv, Israel.
Hepatology. 1996 Aug;24(2):419-23. doi: 10.1053/jhep.1996.v24.pm0008690414.
The coexistence of hyperkinetic circulation, hypermetabolism, and hyperactivity of the sympathetic nervous system is encountered in both cirrhosis and hyperthyroidism. Several drugs, such as propylthiouracil and propranolol, that are beneficial for treating some patients with chronic liver diseases are also prescribed for the treatment of thyrotoxicosis. We investigated the effects of experimentally induced hypo- and hyperthyroidism on the development of cirrhosis induced in rats by thioacetamide (TAA). We specifically examined whether hypothyroidism could prevent and hyperthyroidism could aggravate liver damage. Hypothyroidism induced by methimazole (MMI, 0.04%), propylthiouracil (PTU 0.05%), and by thyroidectomy was confirmed by a significant elevation of thyroid-stimulating hormone (TSH) levels. Hyperthyroidism (decreased TSH levels) was induced by eltroxin (ELT:50 micrograms/kg). Thirteen groups of 10 rats each were studied: euthyroid controls (3 groups: water, TAA 1.5 months, and TAA 3 months), hypothyroid (6 groups: MMI, PTU, surgical, MMI-TAA, PTU-TAA, surgical-TAA), and hyperthyroid (4 groups:ELT 1.5 months and 3 months, and ELT-TAA for 1.5 months and 3 months). Hepatic fibrosis (scored from 0 to 3) was significantly reduced (P < .0001) in hypothyroid rats as compared with euthyroid controls, and was aggravated in TAA-treated hyperthyroid rats (P < .0001). Quantitative microscopic analysis of liver biopsy specimens from all groups confirmed the semiquantitative histopathological scores (P < .001). Direct intrasplenic pressure measurement revealed a significant portal pressure elevation in the TAA and the ELT-treated rats (from 4.7 +/- 0.1 in the euthyroid group to 8.1 +/- 2.3 and 10.2 +/- 2.1 and 12.5 +/- 1.6 in the TAA, ELT and ELT-TAA groups, respectively). However, in the hypothyroid-TAA groups, the portal pressure was found to be within the euthyroid normal range (4.6 +/- 1.2 and 5.8 +/- 0.6 in the PTU-TAA and surgical-TAA, respectively). After 12 weeks, the mean spleen weight of rats receiving only TAA was significantly higher than the TAA-treated hypothyroid rats (P < .0001), indicating that the hypothyroid TAA-treated rats were less portal hypertensive. These results suggest that induced hypothyroidism can inhibit, whereas hyperthyroidism can aggravate, the development of cirrhosis in a rat model.
在肝硬化和甲状腺功能亢进症中均会出现高动力循环、高代谢以及交感神经系统功能亢进并存的情况。几种对治疗某些慢性肝病患者有益的药物，如丙硫氧嘧啶和普萘洛尔，也被用于治疗甲状腺毒症。我们研究了实验性诱导的甲状腺功能减退和亢进对硫代乙酰胺（TAA）诱导的大鼠肝硬化发展的影响。我们特别研究了甲状腺功能减退是否可以预防以及甲状腺功能亢进是否会加重肝损伤。通过促甲状腺激素（TSH）水平显著升高证实了由甲巯咪唑（MMI，0.04%）、丙硫氧嘧啶（PTU 0.05%）以及甲状腺切除术诱导的甲状腺功能减退。通过左旋甲状腺素（ELT：50微克/千克）诱导甲状腺功能亢进（TSH水平降低）。对13组大鼠进行研究，每组10只：甲状腺功能正常的对照组（3组：水、TAA处理1.5个月、TAA处理3个月）、甲状腺功能减退组（6组：MMI、PTU、手术、MMI-TAA、PTU-TAA、手术-TAA）以及甲状腺功能亢进组（4组：ELT处理1.5个月和3个月，以及ELT-TAA处理1.5个月和3个月）。与甲状腺功能正常对照组相比，甲状腺功能减退大鼠的肝纤维化（评分从0到3）显著降低（P <.0001），而在TAA处理的甲状腺功能亢进大鼠中肝纤维化加重（P <.0001）。对所有组肝活检标本的定量显微镜分析证实了半定量组织病理学评分（P <.001）。直接脾内压力测量显示，TAA组和ELT处理组大鼠的门静脉压力显著升高（甲状腺功能正常组为4.7±0.1，TAA组、ELT组和ELT-TAA组分别为8.1±2.3、10.2±2.1和12.5±1.6）。然而，在甲状腺功能减退-TAA组中，门静脉压力处于甲状腺功能正常的正常范围内（PTU-TAA组和手术-TAA组分别为4.6±1.2和5.8±0.6）。12周后，仅接受TAA处理的大鼠的平均脾脏重量显著高于接受TAA处理的甲状腺功能减退大鼠（P <.0001），这表明接受TAA处理的甲状腺功能减退大鼠的门静脉高压程度较轻。这些结果表明，诱导的甲状腺功能减退可以抑制，而甲状腺功能亢进可以加重大鼠模型中肝硬化的发展。
