Department of Pharmacology, Medical College of Soochow University, Suzhou, Jiangsu Province, China.
Planta Med. 2011 Feb;77(3):231-5. doi: 10.1055/s-0030-1250268. Epub 2010 Aug 17.
The objectives of this study were to determine the effect of osthole on the insulin resistance (IR) in high-fat and high-sucrose-induced fatty liver rats and to investigate its potential mechanisms. The rat model was established by orally feeding high-fat and high-sucrose emulsion by gavage for 9 weeks. The experimental rats were treated with osthole 5 and 10 mg/kg, lipanthyl 30 mg/kg, and rosiglitazone 4 mg/kg after oral high-fat and high-sucrose emulsion for 6 weeks and were sacrificed 4 weeks after administration. The total cholesterol (TC), triglycerides (TG), and free fatty acids (FFA) in serum and hepatic tissue, fasting blood glucose (FBG), fasting serum insulin (FINS), serum adiponectin, and liver weight were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) and coefficient of hepatic weight were calculated. The results showed that after treatment with osthole, the serum levels of TC, TG, and FFA, the contents of TG and FFA in hepatic tissue, and body weight gain were lowered, especially in the osthole 10 mg/kg group (p < 0.05 or p < 0.01). Moreover, the histological evaluation of liver specimens demonstrated that the steatosis and inflammation in liver in osthole-treated groups were improved, especially in the 10 mg/kg group (p < 0.05). Importantly, the levels of FBG, FINS, and HOMA-IR in the osthole 10 mg/kg group were decreased (p < 0.01), while the level of serum adiponectin in the osthole-treated groups, like PPAR α agonist lipanthyl and PPAR γ agonist rosiglitazone, was increased (p < 0.05). These results revealed that osthole could improve the IR induced by high-fat and high-sucrose emulsion in fatty liver rats, and its mechanism might be associated with increment of adiponectin release via activation of PPAR α/ γ pathway.
本研究旨在探讨蛇床子素对高脂高糖诱导的脂肪肝大鼠胰岛素抵抗（IR）的影响，并探讨其潜在机制。通过灌胃高脂高糖乳剂 9 周建立大鼠模型。实验大鼠在口服高脂高糖乳剂 6 周后给予蛇床子素 5 和 10mg/kg、力平脂 30mg/kg 和罗格列酮 4mg/kg 治疗，并在给药 4 周后处死。测量血清和肝组织中的总胆固醇（TC）、甘油三酯（TG）和游离脂肪酸（FFA）、空腹血糖（FBG）、空腹血清胰岛素（FINS）、血清脂联素和肝重。计算胰岛素抵抗的稳态模型评估（HOMA-IR）和肝重系数。结果表明，蛇床子素治疗后，血清 TC、TG 和 FFA 水平、肝组织中 TG 和 FFA 含量以及体重增加均降低，尤以蛇床子素 10mg/kg 组降低更为显著（p<0.05 或 p<0.01）。此外，肝组织学评价显示，蛇床子素治疗组肝脂肪变性和炎症均得到改善，尤以 10mg/kg 组改善更为显著（p<0.05）。重要的是，蛇床子素 10mg/kg 组的 FBG、FINS 和 HOMA-IR 水平降低（p<0.01），而血清脂联素水平在蛇床子素治疗组升高，类似于 PPARα 激动剂力平脂和 PPARγ 激动剂罗格列酮（p<0.05）。这些结果表明，蛇床子素可改善高脂高糖乳剂诱导的脂肪肝大鼠的 IR，其机制可能与通过激活 PPARα/γ 通路增加脂联素释放有关。
