衢枳壳黄酮对高脂血症金黄地鼠降血脂作用及其机制研究

Study on Hypolipidemic Effect of Pure Total Flavonoids from Qu Aurantii Fructus on Golden Hamsters of Hyperlipidemia and Its Potential Mechanism

关键词:  高脂血症  衢枳壳黄酮  脂质水平  PPAR-α  PPAR-γ

Key words:  hyperlipidemia  pure total flavonoids from Qu Aurantii Fructus  lipid level  PPAR-α  PPAR-γ

摘要:

目的 研究衢枳壳黄酮（pure total flavonoids from Qu Aurantii Fructus，PTFC）对高脂血症金黄地鼠降血脂作用并初步探讨其潜在机制。方法 48只金黄地鼠随机分为6组（n=8）：正常组，模型组，非诺贝特阳性对照组（100 mg·kg^-1·d^-1），PTFC低、中、高剂量组（25，50，100 mg·kg^-1·d^-1）。高脂饮食喂养金黄地鼠6周，并于第3周起同时给予药物灌胃干预，连续干预4周。高脂饲料喂养造模6周末，处死大鼠，称量大鼠体质量及肝脏质量计算肝脏指数，生化法及ELISA法检测血清生化及炎症指标，血清及肝组织MDA含量和SOD活性。HE染色检测肝脏组织病理学改变，qRT-PCR及Western blotting检测肝脏及脂肪组织PPAR-α、PPAR-γ的mRNA及蛋白表达。结果 与高脂血症模型组金黄地鼠相比，PTFC中、高剂量组的金黄地鼠血清TC、TG、LDL-c、IL-6、TNF-α水平显著下降（P<0.05或P<0.01）；PTFC高剂量组血清ALT、AST、GLU水平均明显下降（P<0.05或P<0.01）；PTFC低、中、高剂量组金黄地鼠的血清、肝脏SOD活性均显著增强，MDA含量则显著降低（P<0.01）。HE染色显示，与模型组比较，各用药组金黄地鼠的肝脂肪变性均得到不同程度的改善。qRT-PCR和Western blotting检测结果显示，与模型组相比，PTFC给药低、中、高剂量组金黄地鼠肝脏和脂肪中PPAR-α、PPAR-γ的mRNA和蛋白表达水平也显著升高（P<0.05或P<0.01）。结论 PTFC能够起到降低血脂的作用，其可能是通过改善脂质水平，降低氧化应激和炎症反应，激活PPAR-α、PPAR-γ来实现对高脂血症金黄地鼠脂质代谢的改善作用。

Abstract:

OBJECTIVE To investigate the hypolipidemic effect of pure total flavonoids from Qu Aurantii Fructus(PTFC) on Hamsters of Hyperlipidemia and its potential mechanism. METHODS Forty eight golden hamsters were randomly divided into control group, model group, fenofibrate group(100 mg·kg^-1·d^-1), PTFC low, medium and high dosages groups(25, 50, 100 mg·kg^-1·d^-1). Firstly, golden hamsters were fed with high fat diet for 6 weeks, at the same time, golden hamsters were administrated intragastrically with PTFC from the 3 week to 6 week. Six weeks after high fat diet, golden hamsters were euthanized, serum biochemical indices and inflammatory factors, MDA content and SOD activity in serum and liver were detected by biochemical method and ELISA assay. The pathological changes of the liver tissues were observed by HE staining; the mRNA and protein expression of PPAR-α and PPAR-γ were determined by qRT-PCR and Western blotting assay. RESULTS PTFC significantly reduced the serum lipid levels of TC, TG, LDL-c, IL-6 and TNF-α in 50 and 100 mg·kg^-1·d^-1 doses(P<0.05 or P<0.01); and the liver function related factors ALT, AST and GLU levels in high does. The content of MDA were significantly reduced and SOD activity were significantly recovered in serum and liver after PTFC administration(P<0.01). The liver pathological results confirmed that the liver pathological injury of golden hamster treated with PTFC was significantly improved compared with that of model group. The mRNA and protein expressions of PPAR-α and PPAR-γ in liver and adipose tissue were also significantly activated with PTFC administration in different doses(P<0.05 or P<0.01). CONCLUSION PTFC has potential hypolipidemic effect in hamsters of hyperlipidemia, and this might owing to the attenuating of lipid levels, antioxidant and anti-inflammatory effects, and the activation of PPAR-α and PPAR-γ in hyperlipoidemia hamsters.