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首页> 外文期刊>The Internet Journal of Pharmacology >The Effect Of Interferon Alone Or Combined With Silymarin On Liver And Bone Parameters In Bile Duct Ligated Rats
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The Effect Of Interferon Alone Or Combined With Silymarin On Liver And Bone Parameters In Bile Duct Ligated Rats

机译：干扰素单独或与水飞蓟素联合对胆管结扎大鼠肝，骨参数的影响

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Thirty-six rats with biliary obstruction induced by double ligation and section of the common bile duct were randomly and blindly assigned to receive subcutaneous injection of interferon alpha (INF-alpha at ?6750 or 13500 IU/kg) three times weekly alone, a combination of INF-alpha and silymarin (25 mg/kg once a day orally) or saline, starting one day after surgery and continued for one month. At the end of the treatment period, rats were killed and analyzed for blood biochemistry, liver and bone histopathology. The administration of INF-alpha at 6750 IU/kg increased plasma aspartate aminotransferase by 60.6%. Serum alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase activities were markedly raised after INF-alpha 13500 U/kg by 74.6%, 89% and 109%, respectively. Such elevations in liver enzymes were not observed in rats treated with a combination of INF-alpha and silymarin. Serum bilirubin decreased by 30.8 and 36.1% after treatment with INF-alpha at 6750 and 13500 IU/kg and by 23.7 and 20.8% after treatment with INF-alpha at 6750 or 13500 IU/kg combined with silymarin, respectively. Calcium levels in plasma were not significantly altered by INF-alpha alone or combined with silymarin. On histology, INF-alpha at 6750 IU/kg failed to prevent fibrosis in liver of BDL rats, although many of the hepatocytes appeared normal, while the higher dose of resulted in some improvement in the degree of fibrosis, oedema and lymphocytic infiltration. The addition of silymarin to interferon did not result in further histological improvement. In contrast to observations in the liver, thickness of bone tissue at the diaphysis of tibia was reduced in BDL rats, but restored to normal values by treatment with INF-alpha alone or by the combination of INF-alpha and silymarin. The high dose of interferon either alone or accompanied with silymarin made much improvement in the bone changes that resulted from bile duct legation These results suggest that INF-alpha alone or co-administered with silymarin is of limited value in this model of cholestatic liver injury, but appear to prevent bone alterations in obstructive jaundice INF-alpha is likely to exert antifibrotic effects distinct from its antiviral properties. The study also indicates that bile duct ligation is a reliable and efficient model for producing osteoporosis in rats for the assessment of different drugs and pathophysiologic mechanisms involved. Introduction Interferon alpha (INF-alpha) alone or in combination with ribavirin is the standard treatment for chronic hepatitis C virus infection. The aim is to eradicate the virus, suppress the continuing necro-inflammatory process and consequently preventing the development of cirrhosis1,2. The latter is the end result of fibrosis characterized by the excessive production of extracellular matrix proteins in the liver, including type I collagen3,4. In human liver, fibrogenesis underlies development of hepatocellular carcinoma (HCC) in 90% of cases, and HCC is an ominous complication of cirrhosis in 30% of the patients5. Despite the fact that therapy with interferon and ribavirin can eliminate the virus and prevent the progression of the disease, frequent side effects and relapses preclude the use of this form of therapy in a substantial proportion of patients. Such combination of interferon and ribavirin is associated with fatigue, influenza-like symptoms (headaches, fever, myalgia), hematologic abnormalities, and neuropsychiatric symptoms6. From 10 to 14% of participants in the registration trials for combination therapy involving the peginterferons withdrew prematurely from therapy due to adverse events7. This is in addition to the fact that sustained response is obtained in approximately 55% of patients with the combination of PEG-IFN and ribavirin6,8. Whether INF-alpha possesses antifibrotic or hepatoprotective properties distinct from its antiviral effect are not clear. There is evidence to suggest that interferon-alp
机译：双盲结扎胆总管和胆总管的胆道梗阻大鼠36只随机和盲目接受皮下注射干扰素-α（INF-α≥6750或13500 IU / kg），每周三次，组合在术后一天开始并持续一个月的INF-α和水飞蓟素（每天口服一次25 mg / kg）或生理盐水。在治疗期结束时，处死大鼠并分析血液生化，肝和骨组织病理学。以6750 IU / kg的INF-alpha给药可使血浆天冬氨酸转氨酶增加60.6％。 INF-alpha 13500 U / kg后，血清碱性磷酸酶，丙氨酸氨基转移酶和天冬氨酸氨基转移酶活性分别显着提高了74.6％，89％和109％。在用INF-α和水飞蓟素联合治疗的大鼠中未观察到肝酶的这种升高。用6750和13500 IU / kg的INF-α治疗后，血清胆红素分别下降30.8％和36.1％;用6750或13500 IU / kg的INF-α与水飞蓟素联合治疗后，血清胆红素分别下降23.7和20.8％。单独使用INF-α或与水飞蓟素联合使用，血浆中的钙水平没有明显改变。在组织学上，尽管许多肝细胞看起来正常，但6750 IU / kg的INF-α未能预防BDL大鼠肝脏的纤维化，而较高剂量的INF-α可以改善纤维化，水肿和淋巴细胞浸润的程度。在干扰素中添加水飞蓟素并没有进一步改善组织学。与在肝脏中观察到的相反，在BDL大鼠中，胫骨骨干处的骨组织厚度减小，但是通过单独使用INF-α或通过INF-α和水飞蓟素的组合恢复到正常值。单独或与水飞蓟素一起使用时，高剂量的干扰素可大大改善因胆管绑扎而导致的骨骼变化。这些结果表明，单独的INF-α或与水飞蓟素共同使用在这种胆汁淤积性肝损伤模型中价值有限，但似乎可以预防阻塞性黄疸中的骨骼改变INF-α可能发挥与其抗病毒特性不同的抗纤维化作用。该研究还表明，胆管结扎术是一种在大鼠中产生骨质疏松症的可靠而有效的模型，用于评估所涉及的不同药物和病理生理机制。引言单独或与利巴韦林联合使用干扰素α（INF-alpha）是慢性丙型肝炎病毒感染的标准治疗方法。目的是消灭病毒，抑制持续的炎性炎症过程，从而预防肝硬化1,2。后者是纤维化的最终结果，其特征是肝脏中细胞外基质蛋白（包括I型胶原3,4）的过量产生。在人类肝脏中，纤维化是90％肝细胞癌（HCC）发展的基础，而HCC在30％的患者中是肝硬化的不祥并发症[5]。尽管事实上干扰素和利巴韦林的疗法可以消除病毒并预防疾病的发展，但频繁的副作用和复发仍使相当一部分患者无法使用这种疗法。干扰素和利巴韦林的这种组合与疲劳，流感样症状（头痛，发烧，肌痛），血液学异常和神经精神症状有关。由于不良事件，涉及聚乙二醇干扰素的联合疗法注册试验的参与者中有10％至14％提前退出治疗7。除此之外，大约有55％的患者使用PEG-IFN和利巴韦林6,8获得了持续应答。尚不清楚INF-α是否具有不同于其抗病毒作用的抗纤维化或肝保护特性。有证据表明干扰素

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