戈娜,梁惠,刘颖,等.海兔素对慢性酒精性肝损伤大鼠肝超微结构及NO和iNOS的影响△[J].中国海洋药物,2014,33(3):. |
海兔素对慢性酒精性肝损伤大鼠肝超微结构及NO和iNOS的影响△ |
Effects of Aplysin on ultrastructure, NO and iNOS in rats with chronic alcoholic liver injury |
投稿时间:2013-11-04 修订日期:2013-12-31 |
DOI: |
中文关键词: 海兔素 酒精性肝损伤 一氧化氮 一氧化氮合酶 超微结构 |
English Keywords:Aplysin alcoholic liver injury nitricoxide nitrogen oxidesynthenase ultrastructure |
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中文摘要: |
目的 研究海兔素(Aplysin)对酒精所致慢性肝损伤大鼠一氧化氮(NO)水平和诱导型一氧化氮合酶 (iNOS)活性及表达的影响,探讨海兔素对酒精性肝损伤的保护作用。方法 雄性Wistar大鼠50只,按体重随机分为5组,每组10只。酒精模型组以50 % 酒精8 mL/(kg?bw?d)灌胃2周后,12 mL/(kg?bw?d)灌胃4周;海兔素低、中、高剂量组酒精剂量同模型组,同时每日分别给予海兔素50、100、150 mg/(kg?bw?d)灌胃;正常组以等体积生理盐水灌胃,持续6周。用透射电镜观察大鼠肝脏超微结构变化;用比色法检测血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)和一氧化氮合酶(NOS)活性以及一氧化氮(NO)含量;采用Western blotting检测大鼠肝脏中iNOS蛋白表达水平的变化。结果 透射电镜下,各剂量海兔素组肝线粒体、内质网结构均较模型组明显改善。与正常组比较,酒精模型组大鼠血清ALT、AST、TNOS和iNOS的活性明显增加,NO含量升高 (P<0.05);而不同剂量的海兔素组和酒精模型组相比,血清ALT、AST、TNOS、iNOS活性以及NO含量均有不同程度地降低,且成剂量依赖关系,然而彼此间并无统计学差异。此外,中、高剂量海兔素可明显抑制大鼠肝组织中iNOS的蛋白表达( P<0.05)。结论 iNOS和NO在慢性酒精性肝损伤中起促进作用,海兔素可能通过抑制体内iNOS活性,下调了体内iNOS蛋白表达,减少NO生成,最终达到保护肝脏的作用。 |
English Summary: |
Objective To explore the protective effects of Aplysin on level of nitric oxide, activity and protein level of nitric oxide sythase in rats with chronic alcoholic liver injury. Methods Male Wistar rats (n=10 for each group) were randomLy divided into the following five groups. Apart from the rats in the normal control group, the other animals were initially administered orally with 50% (v/v) ethanol 8 mL/(kg?bw?d) 1 h after the doses of Aplysin for 2 weeks following by an increasing intake of ethanol up to 12 mL/(kg?bw?d)for the remaining 4 weeks. Meanwhile the alcohol Aplysin-treated groups were administered daily Aplysin doses (i.e., low, medium, and high) of 50, 100, 150 mg/(kg?bw?d), respectively, by gavage for 42 consecutive days; the other groups received an equal volume of vehicle as a control. Ultrastructural changes in the livers of rats were observed by transmission electron microscope (TEM). The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide sythase (NOS) and nitric oxide (NO) content in serum were determined by colorimetric method. The protein expression of iNOS in liver was detected by Western blotting. Results hepatic ultrastructure lesions were reduced in different doses Aplysin groups compared with alcohol model group. Compared with the control group, the activities of serum aminopherase and NOS, NO level were significantly increasing in the alcohol group (P<0.05). Administration of Aplysin significantly decreased the elevation of serum serum aminopherase and NOS activities and NO levels in a dose-dependent manner; however, there were no significant differences between the Aplysin treatment groups (P > 0.05). In addition, medium-, and high-dose Aplysin can significantly inhibit the expression of iNOS(P<0.05). Conclusion NO and iNOS were involved in the chronic liver injury induced by alcohol. However, Aplysin has protective effect on chronic alcoholic liver injury, and the mechanism may be associated with inhibition of iNOS activities, down-regulation of iNOS expression and decrease of NO output. |
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