西红花酸改善大鼠酒精性脂肪肝作用机制研究

Study of mechanism of action for crocetin on alcoholic fatty liver rats

目的研究西红花酸对酒精性脂肪肝大鼠的作用及其机制。方法将30只雄性SD大鼠随机分为健康对照组、模型组及西红花酸组,每组各10只。模型组及西红花组大鼠均行酒精性脂肪肝造模,同时西红花酸组予西红花酸50 mg/(kg·d)灌胃预防性治疗。比较3组大鼠血清丙氨酸氨基转移酶(ALT)、甘油三酯(TG)水平及肝脏极低密度脂蛋白(VLDL)分泌速率,肝脏TG、游离脂肪酸(FFA)含量,肝脏脂肪酸线粒体β-氧化速率及脂肪酸过氧化物酶体β-氧化速率,苯胺羟化酶(ANH)、乙醇脱氢酶(ADH)及乙醛脱氢酶(ALDH)活性,肝脏超氧化物歧化酶(SOD)活性、谷胱甘肽(GSH)含量及丙二醛(MDA)含量。结果模型组与西红花酸组大鼠血清ALT和TG含量、肝脏TG和FFA含量、肝质量系数均高于健康对照组(P<0.01,P<0.05),而西红花酸组均低于模型组(P<0.01,P<0.05);模型组及西红花酸组大鼠肝脏脂肪酸线粒体β-氧化速率、过氧化物酶体β-氧化速率和VLDL分泌速率均低于健康对照组(P<0.05,P<0.01),且西红花酸组脂肪酸线粒体β-氧化速率高于模型组(P<0.05);与健康对照组比较,模型组ANH活性及MDA含量升高(P<0.05),ADH、ALDH、SOD活性及GSH含量降低(P<0.01),而西红花酸组ANH活性及MDA含量较模型组降低(P<0.05),ADH、ALDH、SOD活性及GSH含量升高(P<0.05)。结论西红花酸对酒精性脂肪肝有改善作用,其作用机制可能是通过加速肝脏线粒体脂肪酸氧化,增强血浆中TG消除速度,减轻肝脏脂肪堆积,增强ALDH活性,进而加速乙醇和乙醛的清除。

Objective To investigate the improving effect of crocetin in rats with alcoholic fatty liver, and to elucidate the possible mechanism. Methods 30 SD rats were randomly divided into three groups, health control group, model group and crocetin group. Rats in model group andcrocetin group were prepared alcoholic fatty liver model by feeding high lipid diet plus alcohol forl0 weeks. Rats in crocetin group received crocetin [ 50 mg/ （ kg · d） ] by intragastric administration. Then,liver index, TG, FFA, rate of VLDL - secretion, activity of aniline hydroxylase （ANH）, alcohol dehydrogenase （ADH）, aldenhyde dehydrogenase （ALDH）, SOD and MDA were measured. Alanine aminotransferase （ALT） activity and TG concentration in serum andpathological changes in liver were also observed. Results The contents of ALT and TG inserum, TG and FFA content of liver and liver weight coefficient in model group and crocetingroup were higher than those in health control group （P 〈0.01, P 〈0.05）. Those in crocetin group were lower than those in model group （P 〈0.01, P 〈0.05）. Fatty acid mitochondria beta oxidation rate, the peroxisomal beta oxidation rate and VLDL - secretion rate in model group and crocetingroup were lower than those in healthy controls （ P 〈 0.01, P 〈 0.05 ）. Fatty acid mitochondria beta oxidation rate in crocetin group was higher than that in model group （ P 〈 0.05 ）. Compared with those in health control group, ANH activity and MDA concentration were increased in model group （ P 〈 0.05 ）. The activities of ADH, ALDH and SOD and GSH concentration were decreased （ P 〈 0.01 ）. ANH activity and MDA concentration in crocetin group were decreased in comparison with those in model group （ P 〈 0.05 ）. The activities of ADH, ALDH and SOD and GSH concentration were increased （ P 〈 0.05 ）. Conclusion Crocetin can improve alcoholic fatty liver rats. This effect relates to the increase of liver mitochondrial fatty acid oxidation, reduction of fatty sediment, inhibition of lipid peroxidation, and acceleration of the elimination of alcohol and aldehyde.