Department of Pharmacology, Medical College of Soochow University, Suzhou 215123, Jiangsu Province, China.
Phytomedicine. 2010 Jul;17(8-9):669-73. doi: 10.1016/j.phymed.2009.10.021. Epub 2009 Dec 29.
Our previous studies found that osthol, an active constituent isolated from Cnidium monnieri (L.) Cusson (Apiaceae), could ameliorate the accumulation of lipids and decrease the lipid levels in serum and hepatic tissue in alcohol-induced fatty liver mice and rats. The objective of this study was to investigate its possible mechanism of the lipid-lowering effect. A mouse model with alcoholic fatty liver was induced by orally feeding 52% erguotou wine by gavage when they were simultaneously treated with osthol 10, 20, 40 mg/kg for 4 weeks. The BRL cells (rat hepatocyte line) were cultured and treated with osthol at 25, 50, 100, 200 microg/ml for 24h. The mRNA expressions of peroxisome proliferator-activated receptor (PPAR) alpha, diacylglycerol acyltransferase (DGAT), 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and cholesterol 7 alpha-hydroxylase (CYP7A) in mouse hepatic tissue or cultured hepatocytes were determined by reverse transcription polymerase chain reaction (RT-PCR). After treatment with osthol, the PPAR alpha mRNA expression in mouse liver and cultured hepatocytes was increased in dose dependent manner, while its related target genes for mRNA expression, e.g., DGAT and HMG-CoA reductase, were decreased, the CYP7A was inversely increased. And osthol-regulated mRNA expressions of DGAT, HMG-CoA reductase and CYP7A in the cultured hepatocytes were abrogated after pretreatment with specific inhibitor of PPAR alpha, MK886. It was concluded that osthol might regulate the gene expressions of DGAT, HMG-CoA reductase and CYP7A via increasing the PPAR alpha mRNA expression.
我们之前的研究发现，蛇床子素是一种从蛇床子（伞形科）中分离出来的活性成分，可改善酒精性脂肪肝小鼠和大鼠的脂质积累并降低血清和肝组织中的脂质水平。本研究旨在探讨其降脂作用的可能机制。通过灌胃给予 52%二锅头酒的方法建立酒精性脂肪肝小鼠模型，同时给予蛇床子素 10、20、40mg/kg 治疗 4 周。BRL 细胞（大鼠肝细胞系）用蛇床子素 25、50、100、200μg/ml 处理 24h。通过逆转录聚合酶链反应（RT-PCR）测定小鼠肝组织或培养的肝细胞中过氧化物酶体增殖物激活受体（PPAR）α、二酰基甘油酰基转移酶（DGAT）、3-羟-3-甲基戊二酰辅酶 A（HMG-CoA）还原酶和胆固醇 7α-羟化酶（CYP7A）的 mRNA 表达。蛇床子素处理后，小鼠肝脏和培养的肝细胞中 PPARαmRNA 表达呈剂量依赖性增加，而其相关的靶基因如 DGAT 和 HMG-CoA 还原酶的 mRNA 表达则降低，CYP7A 则相反增加。并且，在用 PPARα的特异性抑制剂 MK886预处理后，蛇床子素调节培养的肝细胞中 DGAT、HMG-CoA 还原酶和 CYP7A 的 mRNA 表达被阻断。结论：蛇床子素可能通过增加 PPARαmRNA 表达来调节 DGAT、HMG-CoA 还原酶和 CYP7A 的基因表达。
