腺苷蛋氨酸对大鼠乙醇肝损伤的预防作用

来源:岁月联盟 作者: 时间:2010-07-12

          作者:李涛,张永强,刘利兵,于军,陈健康,吴昊

【关键词】  肝疾病

    Preventive effect of SadenosylLmethionine from alcoholic liver injury in rats

  【Abstract】 AIM: To investigate the protective effects of SadenosylLmethionine (SAM) on alcoholic liver diseases. METHODS:  Seventeen SD rats were randomly divided into 3 groups: alcohol control group, highdosage SAM group and lowdosage SAM group. Control group was only fed intragastrically with alcohol 6 mL/(kg・d) to establish the alcoholic liver injury model. The high and lowdosage SAM groups were injected with SAM at the dosage of 16 mg/(kg・d) and 32 mg/(kg・d) respectively before they were fed intragastrically with alcohol [6 mL/(kg・d)] to observe the preventative effect. All the rats were killed on the 26th day. γGT was examined and liver pathological sections were observed. RESULTS:  The increasing trend of γGT in serum was significantly inhibited[(72±16) nkat/L vs (2437±362) nkat/L, P<0.01;(88±8) nkat/L vs (2437±362) nkat/L, P<0.05]. The histopathology showed that SAM had some protective effects on the liver function. CONCLUSION:  SAM can reduce the alcoholrelated injury of liver.

  【Keywords】 SAM; liver disease, alcoholic; liver/injuries

  【摘要】 目的:观察S腺苷L甲硫氨酸(SAM)对乙醇性肝损伤的预防作用. 方法:SD大鼠17只随机分为3组,即乙醇对照组和高、低剂量SAM预防组. 乙醇对照组用白酒灌胃来建立乙醇性肝损伤模型,SAM高、低剂量预防组在乙醇灌胃前肌注SAM观察预防作用. 26 d处死大鼠,测血清γGT,进行肝组织病观察. 结果:SAM能明显降低实验性乙醇肝损伤血清γGT的活性[(72±16) nkat/L vs (2437±362) nkat/L,P<0.01;(88±8) nkat/L vs (2437±362) nkat/L,P<0.05]. 乙醇对照组可见汇管区重度充血,淋巴细胞浸润,肝细胞中、重度嗜酸性变或伴片状坏死;高剂量SAM预防组可见轻度淋巴细胞浸润、肝细胞嗜酸性变;低剂量SAM预防组可见肝细胞空泡变性,轻度嗜酸性变,肝窦充血,Kupffer细胞轻度增生. 结论:SAM对实验性乙醇性肝损伤有一定的预防作用.

  【关键词】 S腺苷甲硫氨酸;肝疾病,酒精性;肝/损伤

  0引言

  S腺苷L甲硫氨酸(SadenosylLmethionine, SAM)对乙醇性肝损伤有作用,体外补充SAM能有效改善乙醇性肝病[1]. 临床治疗乙醇性肝病有一定效果[2]. 我们给大鼠肌注SAM后,乙醇灌胃,观察SAM对实验性乙醇肝损伤的预防作用.

  1材料和方法

  1.1材料

  SD成年大鼠17只,体质量(240±10)g,雌雄各半,二级实验动物标准,第四军医大学实验动物中心提供. SAM为德国基诺药厂粉针剂,实验用酒为56度北京二锅头.

  1.2方法

  将大鼠随机分为乙醇对照组(n=6)和高(n=4)、低剂量(n=7) SAM预防组. 乙醇对照组每日下午定时白酒灌胃6 mL/kg;高、低剂量SAM预防组每日上午定时分别肌注SAM 32和16 mg/kg,下午定时白酒灌胃6 mL/kg. 实验两组连续给酒25和26 d取血作酶学检测并处死所有大鼠取肝脏制作石蜡切片,HE染色病理学观察. 血清γ谷氨酰转肽酶(γglutramyl transpeptidase, γGT)由第四军医大学口腔检验科检测.

  统计学处理:数据用x±s表示,采用SPSS 12.0统计软件. 组间比较用Wilcoxon秩和检验分析,检验水准α=0.05,P<0.05表示有显著性差异.

  2结果

  2.1实验性乙醇肝损伤的建立对照组大鼠每日定时白酒灌胃6 mL/kg,26 d后检测血清γGT:(2437±362) nkat/L,明显高于正常范围(Tab 1,P<0.01),HE染色病观察汇管区重度充血,淋巴细胞浸润,中、重度嗜酸性变或伴片状坏死. 表明实验性乙醇肝损伤模型建立成功.表1实验性乙醇肝损伤模型大鼠血清γGT(略)

  2.2肝组织病理学改变乙醇对照组可见汇管区重度充血,淋巴细胞浸润,肝细胞中度嗜酸性变,片状坏死;高剂量SAM预防组可见轻度淋巴细胞浸润、肝细胞嗜酸性变;低剂量SAM预防组可见肝细胞空泡变性,轻度嗜酸性变,肝窦充血(Fig 1A~C).

  3讨论

  在乙醇性肝病的不同阶段,蛋氨酸代谢都会出现紊乱. 与柴胡、五灵丸[3]等中药对慢性肝损伤的保护作用不同,SAM能够合成谷胱甘肽(GSH)发挥抗氧化作用从而缓解乙醇性肝损伤的症状. 实验补充蛋氨酸并不能使肝脏疾病得到改善,这主要是由于肝脏疾病损害了催化蛋氨酸合成SAM的蛋氨酸腺苷转移酶(MAT)的活性. Lieber[4]认为SAM是体内真正的必需营养素,而外源性补充SAM均可以显著缓解肝病症状[5]. 由此可见,SAM在保护肝脏免受酒精损伤中发挥着重要作用. γGT主要分布于肾、胰、肝、肠、脑等组织. 因乙醇损伤肝细胞使肝细胞微粒体γGT酶释出,而致血清中此酶含量增高,可作为检测乙醇性肝损伤的一项重要指标. 实验结果显示,高、低剂量SAM预防组γGT明显低于乙醇对照组(P<0.01). 病理切片观察,乙醇对照组的肝细胞嗜酸性变、淋巴细胞浸润和充血明显重于SAM预防组,并伴有片状坏死. 而SAM预防组仅有轻度嗜酸性变、淋巴细胞浸润、脂肪变性和枯否细胞增生. 证明SAM能够有效的减轻乙醇对肝细胞的损伤.

  【】

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