褪黑素对非酒精性脂肪性肝病大鼠游离脂肪酸的影响

Effect of melatonin on the changes of free fatty acids in nonalcoholic fatty liver disease rats

目的：研究褪黑素（MT）对大鼠非酒精性脂肪性肝病（NAFLD）的形成和游离脂肪酸（FFA）的影响,探讨MT防治NAFLD的可能机制.方法：将雄性Wistar大鼠随机分成对照组、模型组和MT低、中、高剂量组（MT1、MT2和MT3组）,每组10只.对照组给予普通饲料喂养,模型组和MT1、MT2及MT3组给予高脂饮食12周.MT各剂量组分别给予MT 2.5、5.0和10.0 mg·kg-1·d-1腹腔注射.12周末处死大鼠,进行肝脏病理学检查,检测大鼠血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、血清及肝脏三酰甘油（TG）、总胆固醇（TC）和FFA水平.结果：大鼠高脂饮食12周成功复制NAFLD模型.与模型组比,MT各剂量组大鼠肝细胞脂肪变性有不同程度的改善;模型组血清ALT水平高于对照组（P＜0.05）,而TG低于对照组（P＜0.05）,模型组大鼠肝匀浆TC、TG亦均明显高于对照组（P＜0.01）.MT1组大鼠血清ALT水平高于对照组（P＜0.05）,MT1组和MT2组血清TG水平均低于对照组（P＜0.05）;MT1组肝匀浆TC及MT1组、MT2组与MT3组TG水平均明显高于对照组（P＜0.01）;MT3组肝匀浆TC水平明显低于模型组（P＜0.01）.模型组大鼠血清FFA水平明显高于对照组（P＜0.01）;与模型组比较,MT各剂量组血清FFA均降低（P＜0.05～P＜0.01）.模型组大鼠肝匀浆FFA水平明显高于对照组（P＜0.01）;MT2、MT3组肝匀浆FFA均明显低于模型组（P＜0.01）.结论：MT对NAFLD的形成有明显防治作用,且与剂量呈正相关,可能与MT降低FFA合成而改善氧化应激和抑制脂质过氧化等有关.

Objective： To investigate the effect of melatonin （MT） on the development of nonalcoholic fatty liver disease （NAFLD） in rats with high fat diet and observe the changes of free fatty acid （ FFA）, to evaluate the protective mechanism of MT on NAFLD. Methods：Fifty male Wistar rats were randomly divided into five groups：control group, model group and the different groups with melatonin at low does ,moderate does and high does（ MT1 ,MT2 and MT3 groups）. The rats in MT1, MT2 and MT3 groups and model group were fed with high fat diet for 12 weeks while with common diet in normal control group. MT was injected intraperitoneally at 2.5 mg.kg^-1 ·d^-1,5.0 mg.kg^-1 ·d^-1 and 10.0 mg.kg^-1 ·d^-1 respectively in MT1,MT2 and MT3 groups. All rats were sacrificed after 12 weeks. Histopathologieal changes in liver were observed. The levels of serum alanine aminotransferase （ ALT）, aspartate aminotransferase （ AST）, serum and hepatic triglyceride （ TG）, total cholesterol （ TC ） and FFA were measured. Results ： High fat diet for 12 weeks established rat NAFLD model successfully. Compared with model group, hepatic steatosis was improved in melatonin-treated groups. Serum AST level in model group was higher than in control group（ P 〈0.05 ） ,while serum TG level was lower than in control group（P 〈 0.05 ）. The levels of hepatic TC and TG were significantly higher than in control group （ P 〈 0.01 ）. Serum ALT level in MT1 group was higher than in control group （ P 〈 0.05） and serum TG level in MT1 and MT2 groups were less than in control group （P 〈 0.05）. The hepatic TC level in MT1 group, the levels of hepatic TG in MT1, MT2 and MT3 groups were higher than in control group （P 〈0.01 ）. The level of hepatic TC in MT3 group was lower than in model group （P 〈0.01 ）. The serum FFA level in model group was higher than in control group（ P 〈 0.05 to P 〈 0.01 ）. Compared with model group, serum FFA level in MT groups were reduced（P 〈0.05 to P 〈0.01 ）. The hepatic FFA level in model group was higher than in control group（P 〈0.01 ）. The hepatic FFAcontent in MT2, MT3 groups were lower than in model group （P 〈 0.01 ）. Conclusions ： Melatonin plays the protective and therapeutic effect for NAFLD in a dose dependent manner, may be related to decreasing the production of FFA which improving oxidative stress and depressing lipid peroxidation in rat with high fat diet.