饲用甜菜碱可防止大鼠连续 1 个月用大鼠灌胃管饲模型灌胃酒精时发生血液酒精循环。
Betaine feeding prevents the blood alcohol cycle in rats fed alcohol continuously for 1 month using the rat intragastric tube feeding model.
机构信息
Harbor-UCLA Medical Center, Torrance, CA 90509, USA.
出版信息
Exp Mol Pathol. 2011 Oct;91(2):540-7. doi: 10.1016/j.yexmp.2011.05.009. Epub 2011 Jun 25.
BACKGROUND
Blood alcohol levels (BAL) cycle up and down over a 7-8 day period when ethanol is fed continuously for one month in the intragastric tube feeding rat model (ITFRM) of alcoholic liver disease. The cycling phenomenon is due to an alternating increase and decrease in the metabolic rate. Recently, we found that S-adenosyl-methionine (SAMe) fed with alcohol prevented the BAL cycle.
METHOD
Using the ITFRM we fed rats betaine (2 g/kg/day) with ethanol for 1 month and recorded the daily 24 h urine ethanol level (UAL) to measure the BAL cycle. UAL is equivalent to BAL because of the constant ethanol infusion. Liver histology, steatosis and BAL were measured terminally after 1 month of treatment. Microarray analysis was done on the mRNA extracted from the liver to determine the effects of betaine and alcohol on changes in gene expression.
RESULTS
Betaine fed with ethanol completely prevented the BAL cycle similar to SAMe. Betaine also significantly reduced the BAL compared to ethanol fed rats without betaine. This was also observed when SAMe was fed with ethanol. The mechanism involved in both cases is that SAMe is required for the conversion of epinephrine from norepinephrine by phenylethanolamine methyltransferase (PNMT). Epinephrine is 5 to 10 fold more potent than norepinephrine in increasing the metabolic rate. The increase in the metabolic rate generates NAD, permitting ADH to increase the oxidation of alcohol. NAD is the rate limiting factor in oxidation of alcohol by alcohol dehydrogenase (ADH). This explains how SAMe and betaine prevented the cycle. Microarray analysis showed that betaine feeding prevented the up regulation of a large number of genes including TLR2/4, Il-1b, Jax3, Sirt3, Fas, Ifngr1, Tgfgr2, Tnfrsf21, Lbp and Stat 3 which could explain how betaine prevented fatty liver.
CONCLUSION
Betaine feeding lowers the BAL and prevents the BAL cycle by increasing the metabolic rate. This increases the rate of ethanol elimination by generating NAD.
背景
在酒精性肝病的胃内管饲大鼠模型（ITFRM）中，连续一个月经胃内管饲给予乙醇时，血液酒精水平（BAL）会在 7-8 天的周期内上下波动。这种循环现象是由于代谢率的交替增加和减少所致。最近，我们发现与酒精一起给予 S-腺苷甲硫氨酸（SAMe）可防止 BAL 循环。
方法
我们使用 ITFRM 给大鼠喂食甜菜碱（2g/kg/天）和乙醇一个月，并记录每天 24 小时的尿乙醇水平（UAL），以测量 BAL 循环。UAL 与 BAL 相当，因为持续输注乙醇。治疗 1 个月后，通过肝组织学、脂肪变性和 BAL 来测量终末结果。从肝脏提取的 mRNA 进行微阵列分析，以确定甜菜碱和乙醇对基因表达变化的影响。
结果
与 SAMe 一样，甜菜碱与乙醇一起喂食完全阻止了 BAL 循环。与未喂食甜菜碱的乙醇喂养大鼠相比，甜菜碱也显著降低了 BAL。当 SAMe 与乙醇一起喂食时也观察到这种情况。这两种情况下涉及的机制是，SAMe 是通过苯乙醇胺甲基转移酶（PNMT）将去甲肾上腺素转化为肾上腺素所必需的。肾上腺素比去甲肾上腺素增加代谢率的作用强 5 到 10 倍。代谢率的增加生成 NAD，允许 ADH 增加酒精的氧化。NAD 是 ADH 氧化酒精的限速因素。这解释了 SAMe 和甜菜碱如何防止循环。微阵列分析表明，甜菜碱喂养可防止包括 TLR2/4、Il-1b、Jax3、Sirt3、Fas、Ifngr1、Tgfgr2、Tnfrsf21、Lbp 和 Stat 3 在内的大量基因的上调，这可以解释甜菜碱如何预防脂肪肝。
结论
甜菜碱喂养通过增加代谢率来降低 BAL 并防止 BAL 循环。这通过生成 NAD 来增加乙醇的消除率。
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