摘要：目的：探讨大蒜素联合维生素C、维生素B6对小鼠非酒精性脂肪性肝病（NAFLD）的防治作用及其机制。方法18只C57BL/6小鼠按随机数字表法随机分成预防组、治疗组和对照组（各6只）。预防组：高脂饲料喂养的同时按体重给予大蒜素0.02 mg/g、维生素C 0.50 mg/g、维生素B60.02 mg/g，每天灌胃1次，连续4周。治疗组：在高脂饲料喂养4周后给予上述药物灌胃治疗1周。对照组：给予高脂饲料喂养4周，同时用等量生理盐水灌胃。处理结束后观察3组小鼠血清ALT、AST、游离脂肪酸（FFA）水平，肝组织超氧化物歧化酶（SOD）、丙二醛（MDA）水平，肝组织诱导型一氧化氮合酶（iNOS）表达及其信使核糖核酸（mRNA）含量，肝组织病理学改变及Kupffer细胞浸润情况。各组计量资料间比较采用单因素方差分析和LSD-t检验。结果预防组、治疗组、对照组小鼠血清ALT平均水平分别为（30±7）、（34±7）、（44±6）U/L，预防组和治疗组明显低于对照组（LSD-t=3.815，2.748；P<0.05）。预防组、治疗组、对照组小鼠血清AST水平分别为（46±6）、（43±8）、（103±7）U/L，预防组和治疗组明显低于对照组（LSD-t=12.400,16.371；P<0.05）。预防组、治疗组、对照组小鼠血清FFA水平分别为（196±10）、（223±12）、（254±31）mmol/L，预防组、治疗组明显低于对照组（LSD-t=4.335,2.271；P<0.05），且预防组明显低于治疗组（LSD-t=4.154, P<0.05）。预防组、治疗组、对照组小鼠肝组织SOD水平分别为（128±17）、（119±30）、（82±13）kU/L，预防组和治疗组明显高于对照组（LSD-t=5.413,2.850；P<0.05）。预防组、治疗组、对照组小鼠肝组织MDA水平分别为（5.5±1.9）（、5.7±1.9）（、7.9±0.9）μmol/L，预防组和治疗组明显低于对照组（LSD-t=2.818,2.527；P<0.05）。对照组小鼠肝组织iNOS蛋白表达较预防组和治疗组明显增强。预防组、治疗组、对照组小鼠肝组织iNOS mRNA含量分别为（3.6±0.5）×10-4，（3.3±0.5）×10-4，（7.5±0.3）×10-4，预防组和治疗组明显低于对照组（LSD-t=13.273,13.976；P<0.05）。对照组小鼠肝脏表现为明显脂肪肝，预防组和治疗组脂肪肝程度较轻。预防组和治疗组小鼠肝组织中的活化Kupffer细胞数量较对照组明显减少。结论大蒜素联合维生素C、维生素B6可有效防治小鼠NAFLD，其机制可能与减轻脂质过氧化损伤、增加肝脏抗氧化能力、抑制Kupffer细胞活性及降低血清FFA水平有关。%Objective To study the role of garlicin, vitamin C and vitamin B6 and the mechanism in preventing and treating non-alcoholic fatty liver disease (NAFLD) in mouse. Methods Eighteen C57BL/6 mice were randomly divided into 3 groups according to the random number table:preventing group, treating group and control group with 6 mice in each group. In preventing group, the mice were fed with high fatty diet and were infused intragastrically with garlicin (0.02 mg/g), vitamin C (0.50 mg/g) and vitamin B6 (0.02 mg/g) by weight everyday at the same time for 4 weeks. In treating group, the mice were infused intragastrically with the above drugs for 1 week after 4 weeks of feeding with high fatty diet. In control group, the mice were fed with high fatty diet and were infused intragastrically with equivalent normal saline at the same time for 4 weeks. After processing, the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), free fatty acids (FFA), levels of superoxide dismutase (SOD), malondialdehyde (MDA), expression of inducible nitric oxide synthase (iNOS), content of messenger ribonucleic acid (mRNA) of iNOS, pathological changes and inifltration of Kupffer cells of liver tissues in 3 groups were observed. The differences of measurement data in 3 groups were compared using one-way analysis of variance and LSD-t test. Results The mean levels of serum ALT were (30±7), (34±7), (44±6) U/L in preventing group, treating group and control group respectively, which were signiifcantly lower in preventing group and treating group than that in control group (LSD-t=3.815, 2.748; P<0.05). The levels of serum AST were (46±6), (43±8), (103±7) U/L in preventing group, treating group and control group respectively, which were significantly lower in preventing group and treating group than that in control group (LSD-t=12.400, 16.371; P<0.05). The levels of serum FFA were (196±10), (223±12), (254±31) mmol/L in preventing group, treating group and control group respectively, which were signiifcantly lower in preventing group and treating group than that in control group (LSD-t=4.335, 2.271; P<0.05), and it was significantly lower in preventing group than that in treating group (LSD-t=4.154;P<0.05). The levels of serum SOD were (128±17), (119±30), (82±13) kU/L in preventing group, treating group and control group respectively, which were signiifcantly higher in preventing group and treating group than that in control group (LSD-t=5.413, 2.850; P<0.05). The levels of serum MDA were (5.5±1.9), (5.7±1.9), (7.9±0.9)μmol/L in preventing group, treating group and control group respectively, which were signiifcantly lower in preventing group and treating group than that in control group (LSD-t=2.818, 2.527; P<0.05). The expression of iNOS protein in liver tissues of mice in control group signiifcantly increased, compared with that in preventing group and treating group. The mRNA contents of iNOS in liver tissues of mice were (3.6±0.5)×10-4, (3.3±0.5)×10-4, (7.5±0.3)×10-4, which were signiifcantly lower in preventing group and treating group than that in control group (LSD-t=13.273, 13.976; P<0.05). Obvious fatty liver was observed in mice of control group, while it was milder in preventing group and treating group. The activated Kupffer cells in liver tissues significantly decreased in preventing group and treating group, compared with that in control group. Conclusions Combined use of garlicin, vitamin C and vitamin B6 is effective in preventing and treating NAFLD. The mechanism may be related with alleviating lipid peroxidation damage, enhancing the oxidation resistance of liver, suppressing cytoactive of Kupffer cells and decreasing the levels of serum FFA.
