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腺苷蛋氨酸对酒精性肝损伤大鼠HHcy和TNF-α的影响 被引量:2

Effects of S-adenosylmethionine on hyperhomocysteinemia and the expression of TNF-α in ethanol-induced liver injury in rats
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摘要 目的观察S-腺苷蛋氨酸(S-adenosylmethionine,SAM)对酒精性肝损伤大鼠的防治作用及机制。方法48只SD大鼠随机分为4组(每组12只):对照组、模型组、腺苷蛋氨酸低、高剂量组。除对照组外,其余三组给予酒精、鱼油灌胃配合高脂饮食构建酒精性肝损伤大鼠模型,造模4周后腹腔注射SAM,第8周处死全部大鼠。测定血浆总同型半胱氨酸(totalplasmahomocysteine,tH-cy)、血清丙氨酸转移酶(ALT)、肝匀浆丙二醛(MDA)和还原型谷胱甘肽(GSH)含量,并应用半定量逆转录聚合酶链反应(RT-PCR)法检测大鼠肝组织TNF-αmRNA水平。结果与对照组比较,模型组大鼠tHcy、ALT、MDA含量均明显升高(P<0·01);GSH水平降低(P<0·01);大鼠肝组织TNF-αmRNA表达明显增强(P<0·01)。与模型组比较,SAM治疗组ALT、MDA明显降低(P<0·05);GSH含量升高(P<0·01);肝组织内TNF-αmRNA水平明显降低(P<0·01);但血浆tHcy水平无显著变化(P>0·05)。结论SAM可明显改善大鼠酒精性肝损伤,其机制可能与其降低肝组织脂质过氧化、抑制肝内TNF-α表达有关,SAM对血浆tHcy水平无显著影响。 Objective To investigate the effects of S-adenosylmethionine (SAM) on ethanol-induced liver injury in rats. Methods 48 female SD rats were randomly divided into 4 groups as control, model, small and large dose SAM groups. Except control group, all rats were fed high fat-containing diet plus ethanol and fish oil gavage for 8 weeks. SAM was administered by intraperitioneal injection after 4 weeks of exposure to ethanol. Plasma total homocysteine (tHcy), serum aminotransferase activity (ALT), liver malondialdehyde (MDA), glutathione (GSH) contents were assayed, and expression of TNF-a was detected by immunohistochemistry, and liver histology was also examined. Results Compared with control group, model group rats developed marked liver damage, accompanied by an increase of tHcy, ALT, and MDA levels, but a decrease of GSH levels (P〈0.01), with a significant elevation of the expression of TNF-a in liver compared to the control group (P〈0.01). In treatment groups, SAM significantly protected the liver from injury, as shown by reduced ALT, MDA (P〈0.01), and enhanced GSH levels (P〈0.01), and abolition of the induced expression of TNF-a either the dose of SAM was large or small. However, plasma total homocysteine levels were not affected significantly by the treatment (P〉0.05). Conclusion SAM prevents alcohol-induced liver injury in rats by reducing liver lipid peroxidation, together with down-regalation of expression of TNF-a. SAM does not affect the plasma total homocysteine levels.
出处 《解放军医学杂志》 CAS CSCD 北大核心 2006年第3期240-242,共3页 Medical Journal of Chinese People's Liberation Army
关键词 肝疾病 酒精性 S-腺苷甲硫氨酸 脂质过氧化作用 半胱氨酸 肿瘤坏死因子 liver diseases, alcoholic S-adenosylmethionine lipid peroxidation cysteine tumor necrosis factor
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  • 1Blasco C,Caballeria J,Deulofeu R et al.Prevalence and mechanisms of hyperhomocysteinemia in chronic alcoholics.Alcohol Clin Exp Res,2005,29(6):1044
  • 2Kharbanda KK,Mailliard ME,Siford GL et al.Comparison of the effects of betaine and S-adenosylmethionine on ethanol-induced changes in methionine metabolism and steatosis in rat hepatocytes.Nutr,2005,135(3):519
  • 3Kishore R,Hill JR,McMullen MR et al.ERK1/2 and Egr1 contribute to increased TNF-α production in rat Kupffer cells after chronic ethanol feeding.Am J PhysiolGastrointest Liver Physiol,2002,282(1):G6
  • 4Song Z,Zhou Z,Uriarte S et al.S-adenosylhomocysteine sensitizes to TNF-alpha hepatotoxicity in mice and liver cells:a possible etiological factor in alcoholic liver disease.Hepatology,2004,40(4):989
  • 5Simile MM,Banni S,Angioni E.5'-Methylthioadenosine administration prevents lipid peroxidation and fibrogenesis induced in rat liver by carbon-tetrachloride intoxication.Hepatol,2001,34(3):386

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