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    188宝金博页面版: [精品]Methimazole Alleviates Hepatic Encephalopathy in Bile-duct Ligated Cirrhotic Rats

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    内容提示： J Chin Med Assoc ? December 2006 ? Vol 69 ? No 1 2563IntroductionHepatic encephalopathy (HE) is a complex neuro-psychiatric syndrome associated with fulminant liverfailure, chronic liver parenchymal disease, or porto-systemic shunting.1–4The symptom of HE varies,including subtle changes in mentality and alertness,disruptions of physiologic circadian rhythm, or acomplete loss of consciousness (hepatic coma). Thepathogenesis of HE is not clearly known at present.Numerous substances, such as ammonia, γ-a...

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    J Chin Med Assoc • December 2006 • Vol 69 • No 1 2563IntroductionHepatic encephalopathy (HE) is a complex neuro-psychiatric syndrome associated with fulminant liverfailure, chronic liver parenchymal disease, or porto-systemic shunting.1–4The symptom of HE varies,including subtle changes in mentality and alertness,disruptions of physiologic circadian rhythm, or acomplete loss of consciousness (hepatic coma). Thepathogenesis of HE is not clearly known at present.Numerous substances, such as ammonia, γ-aminobu-tyric acid, benzodiazepine, aromatic amino acid andfalse neurotransmitter, have been proposed to beinvolved in the development of HE.1–4The results ofprevious studies suggest that the pathogenesis of HEcould be multifactorial.It is known that portal hypertension is a hyper-dynamic circulatory state characterized by generalizedvasodilatation, increased systemic and splanchnic bloodflows and increased cardiac output.5In fact, the hyper-kinetic circulation, hypermetabolism and sympatheticoveractivity can also be found in patients with hyper-thyroidism.6,7Furthermore, in portal hypertensive rats,hypothyroidism induced by methimazole caused ame-lioration of the hyperdynamic circulation followed byreduction of portal pressure.8In conditions with liver parenchymal injury, propyl-thiouracil (PTU), a commonly used antithyroid drug,ORIGINALARTICLEMethimazole Alleviates Hepatic Encephalopathy inBile-duct Ligated Cirrhotic RatsChing-Chih Chang1, Yi-Chou Chen2, Hui-Chun Huang3,4, Fa-Yauh Lee2,3,4*, Full-Young Chang3,4, Han-Chieh Lin3,4, Cho-Yu Chan4,5, Sun-Sang Wang1,4, Shou-Dong Lee3,41T aipei Municipal Gan-Dau Hospital, Divisions of Medicine and 4National Y ang-Ming University School of Medicine, T aipei, T aiwan, R.O.C.2General Medicine and3Gastroenterology, Department of 5Department of Medical Research and Education, T aipei V eterans General Hospital, and Background: Acute or chronic liver damage may lead to hepatic encephalopathy. Previous studies have indicated thehemodynamic and hormonal mimicry between portal hypertension and hyperthyroidism. Furthermore, medically or surgi-cally induced hypothyroidism has been found to be beneficial in ameliorating hyperdynamic circulation in the portalhypertensive state and in alleviating acute or chronic liver injury in rats. However, the effect of chronic thyroid hormoneinhibition on chronic hepatic encephalopathy in cirrhosis remains unknown.Methods: Liver cirrhosis was induced by bile-duct ligation (BDL) in male Sprague-Dawley rats. Three weeks after BDL, ratswere randomized to receive either tap water (control) or 0.04% methimazole in drinking water for 3 weeks. At the end of6 weeks after BDL, severity of encephalopathy was assessed by the Opto-Varimex animal activity meter and hemodynamicparameters were measured. Blood samples were collected for determination of thyroid stimulating hormone, ammoniaand liver biochemistry.Results: The heart rate of the methimazole-treated group was significantly lower than that of the control group (p =0.015),whereas there were no differences in the mean arterial pressure and portal pressure. The total amount of movementswere significantly increased in the methimazole group (p =0.029). Plasma levels of ammonia, aspartate aminotransferaseand alkaline phosphatase were significantly lower (p=0.01) and thyroid stimulating hormone significantly higher (p=0.035)in the methimazole group.Conclusion: Chronic methimazole treatment alleviates hepatic encephalopathy and liver damage in rats with BDL-induced hepatic cirrhosis. [J Chin Med Assoc 2006;69(12):563–568]Key Words: hepatic encephalopathy, liver cirrhosis, methimazole© 2006 Elsevier. All rights reserved.*Correspondence to: Dr Fa-Yauh Lee, Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, R.O.C.E-mail: fylee@vghtpe.gov.tw● Received: June 30, 2006● Accepted: October 23, 2006

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