Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China.
Lipids Health Dis. 2011 Jan 26;10:23. doi: 10.1186/1476-511X-10-23.
Treatment with atorvastatin (ATO) or dietary control has been demonstrated to benefit patients with non-alcoholic fatty liver disease (NAFLD) and hyperlipidemia. However, little is known on whether combination of dietary control and ATO treatment could enhance the therapeutic effect.
We employed a rat model of NAFLD to examine the therapeutic efficacy of dietary control and/or ATO treatment. Sprague-Dawley rats were fed with normal chow diet as normal controls or with high fat diet (HFD) for 12 weeks to establish NAFLD. The NAFLD rats were randomized and continually fed with HFD, with normal chow diet, with HFD and treated with 30 mg/kg of ATO or with normal chow diet and treated with the same dose of ATO for 8 weeks. Subsequently, the rats were sacrificed and the serum lipids, aminotransferase, hepatic lipids, and liver pathology were characterized. The relative levels of fatty acid synthesis and β-oxidation gene expression in hepatic tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Hepatic expression of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was determined by Western blot assay.
While continual feeding with HFD deteriorated NAFLD and hyperlipidemia, treatment with dietary control, ATO or ATO with dietary control effectively improved serum and liver lipid metabolism and liver function. In comparison with ATO treatment, dietary control or combined with ATO treatment significantly reduced the liver weight and attenuated the HFD-induced hyperlipidemia and liver steatosis in rats. Compared to ATO treatment or dietary control, combination of ATO and dietary control significantly reduced the levels of serum total cholesterol and low density lipoprotein cholesterol (LDL-C). However, the combination therapy did not significantly improve triglyceride and free fatty acid metabolism, hepatic steatosis, and liver function, as compared with dietary control alone.
ATO treatment effectively improved NAFLD-related hyperlipidemia and inhibited liver steatosis, accompanied by modulating the expression of genes for regulating lipid metabolism. ATO enhanced the effect of dietary control on reducing the levels of serum total cholesterol and LDL-C, but not triglyceride, free fatty acid and hepatic steatosis in HFD-induced fatty liver and hyperlipidemia in rats.
阿托伐他汀（ATO）治疗或饮食控制已被证明可使非酒精性脂肪肝（NAFLD）和高脂血症患者受益。但是，对于饮食控制和 ATO 联合治疗是否可以增强治疗效果知之甚少。
我们使用 NAFLD 大鼠模型来检查饮食控制和/或 ATO 治疗的治疗效果。Sprague-Dawley 大鼠正常饮食喂养作为正常对照组或高脂饮食喂养 12 周以建立 NAFLD。NAFLD 大鼠随机分为继续高脂饮食组、正常饮食组、继续高脂饮食+ATO30mg/kg 组和正常饮食+相同剂量 ATO 组，连续喂养 8 周。然后处死大鼠，检测血清脂质、氨基转移酶、肝脂质和肝脏病理变化。采用实时定量聚合酶链反应（qRT-PCR）检测肝组织中脂肪酸合成和β氧化基因的相对表达水平。Western blot 法检测肝组织羟甲基戊二酰辅酶 A（HMG-CoA）还原酶的表达。
继续高脂饮食喂养加重了 NAFLD 和高脂血症，而饮食控制、ATO 或 ATO 联合饮食控制治疗可有效改善血清和肝脏脂质代谢及肝功能。与 ATO 治疗相比，饮食控制或 ATO 联合饮食控制治疗显著降低了肝重，并减轻了高脂饮食诱导的大鼠高脂血症和肝脂肪变性。与 ATO 治疗或饮食控制相比，ATO 联合饮食控制治疗显著降低了血清总胆固醇和低密度脂蛋白胆固醇（LDL-C）水平。然而，与单独饮食控制相比，联合治疗并未显著改善甘油三酯和游离脂肪酸代谢、肝脂肪变性和肝功能。
ATO 治疗可有效改善与 NAFLD 相关的高脂血症，并抑制肝脂肪变性，同时调节脂质代谢相关基因的表达。ATO 增强了饮食控制降低 HFD 诱导的脂肪肝和高脂血症大鼠血清总胆固醇和 LDL-C 水平的作用，但不能降低甘油三酯、游离脂肪酸和肝脂肪变性。
