肌肽可改善肝硬化大鼠的肝纤维化和高氨血症。
Carnosine ameliorates liver fibrosis and hyperammonemia in cirrhotic rats.
作者信息
Jamshidzadeh Akram, Heidari Reza, Latifpour Zahra, Ommati Mohammed Mehdi, Abdoli Narges, Mousavi Somayeh, Azarpira Negar, Zarei Azita, Zarei Mahdi, Asadi Behnam, Abasvali Mojgan, Yeganeh Yasaman, Jafari Faezeh, Saeedi Arastoo, Najibi Asma, Mardani Elnaz
机构信息
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, P.O. Box 1583, 71345 Roknabad, Karafarin Street, Shiraz, Fars, Iran; Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, P.O. Box 1583, 71345 Roknabad, Karafarin Street, Shiraz, Fars, Iran.
出版信息
Clin Res Hepatol Gastroenterol. 2017 Sep;41(4):424-434. doi: 10.1016/j.clinre.2016.12.010. Epub 2017 Mar 7.
AIM
Chronic liver injury and cirrhosis leads to liver failure. Hyperammonemia is a deleterious consequence of liver failure. On the other hand, oxidative stress seems to play a pivotal role in the pathogenesis of liver fibrosis as well as in the cytotoxic mechanism of ammonia. There is no promising therapeutic agent against ammonia-induced complications. The present study was conducted to evaluate the role of carnosine (CA) administration on liver pathological changes, elevated plasma ammonia, and its consequent events in cirrhotic rats.
METHODS
Bile duct ligated (BDL) rats were used as a model of cirrhosis. CA (250, 500, and 1000mg/kg, daily, i.p) was administered for 28 consecutive days to BDL animals. At the end of treatments, markers of oxidative stress and liver fibrosis was determined in liver and serum biomarkers of liver injury and plasma ammonia was assessed. Moreover, changes in animals' locomotor activity were monitored.
RESULTS
Severe bridging fibrosis, inflammation, and necrosis in liver, along with elevated serum biomarkers of liver injury were evident in BDL animals. Furthermore, plasma ammonia was drastically elevated in cirrhotic rats and animals' locomotor activity was suppressed. It was found that CA (250, 500, and 1000mg/kg, daily, i.p) significantly alleviated liver injury and its consequent events in cirrhotic rats. The data suggested that CA is not only a useful and safe agent to preserve liver function, but also prevented hyperammonemia and brain damage as a deleterious consequence of cirrhosis and liver failure.
目的
慢性肝损伤和肝硬化会导致肝衰竭。高氨血症是肝衰竭的有害后果。另一方面，氧化应激似乎在肝纤维化的发病机制以及氨的细胞毒性机制中起关键作用。目前尚无针对氨诱导并发症的有效治疗药物。本研究旨在评估肌肽（CA）给药对肝硬化大鼠肝脏病理变化、血浆氨升高及其后续事件的作用。
方法
采用胆管结扎（BDL）大鼠作为肝硬化模型。连续28天每天给BDL动物腹腔注射CA（250、500和1000mg/kg）。治疗结束时，测定肝脏中氧化应激和肝纤维化的标志物，评估肝损伤的血清生物标志物和血浆氨。此外，监测动物的运动活动变化。
结果
BDL动物肝脏出现严重的桥接纤维化、炎症和坏死，同时肝损伤的血清生物标志物升高。此外，肝硬化大鼠血浆氨显著升高，动物的运动活动受到抑制。发现CA（250、500和1000mg/kg，每天腹腔注射）可显著减轻肝硬化大鼠的肝损伤及其后续事件。数据表明，CA不仅是一种保护肝功能的有用且安全的药物，还能预防作为肝硬化和肝衰竭有害后果的高氨血症和脑损伤。
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