Heart Center, Cheng-Hsin General Hospital, Taipei, Taiwan.
Acta Physiol (Oxf). 2013 Feb;207(2):299-307. doi: 10.1111/apha.12005. Epub 2012 Oct 1.
We investigated whether transient receptor potential vanilloid type 1 (TRPV1) was involved in the therapeutic effect of evodiamine, a main bioactive component in the fruit of Evodiae rutaecarpa, on the development of atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice and ApoE(-/-)TRPV1(-/-) mice.
Histopathology was examined by haematoxylin and eosin staining, levels of cytokines and mediators were evaluated by ELISA kits, and protein expression was determined by Western blotting.
Chronic administration with evodiamine (10 mg kg(-1) body weight) reduced the size of atherosclerotic lesions and alleviated the hyperlipidaemia and systemic inflammation, as well as hepatic macrovesicular steatosis, in ApoE(-/-) mice. Treating ApoE(-/-) mice with evodiamine enhanced hepatic cholesterol clearance, as revealed by upregulation of hepatic low-density lipoprotein receptor and ATP-binding cassette (ABC) transporters ABCG5, ABCG8 and cholesterol 7α-hydrolase. Genetic deletion of TRPV1 in ApoE(-/-) mice promoted the progression of atherosclerosis; elevated the serum levels of cholesterol, cytokines and chemokines; and exacerbated hepatic macrovesicular steatosis. Moreover, genetic deletion of TRPV1 abrogated the evodiamine-evoked atheroprotection but not anti-obesity effect in ApoE(-/-) mice.
Evodiamine may confer novel TRPV1-dependent atheroprotection and TRPV1-independent anti-obesity action.
本研究旨在探讨辣椒素瞬时受体电位香草酸亚型 1（TRPV1）是否参与吴茱萸碱（吴茱萸果实的主要生物活性成分）治疗载脂蛋白 E 缺陷（ApoE（-/-））小鼠动脉粥样硬化的作用机制。
采用苏木精-伊红（H&E）染色观察组织病理学变化，ELISA 试剂盒评估细胞因子和介质水平，Western blot 检测蛋白表达。
长期给予吴茱萸碱（10mg/kg 体重）可减轻 ApoE（-/-）小鼠动脉粥样硬化病变的严重程度，改善血脂异常和全身炎症以及肝脏大泡性脂肪变性。吴茱萸碱治疗 ApoE（-/-）小鼠可增强肝脏胆固醇清除能力，表现为肝脏低密度脂蛋白受体和 ATP 结合盒（ABC）转运蛋白 ABCG5、ABCG8 和胆固醇 7α-羟化酶表达上调。在 ApoE（-/-）小鼠中敲除 TRPV1 可促进动脉粥样硬化进展，增加血清胆固醇、细胞因子和趋化因子水平，并加重肝脏大泡性脂肪变性。此外，TRPV1 基因缺失可消除吴茱萸碱对 ApoE（-/-）小鼠的动脉粥样硬化保护作用，但不影响其抗肥胖作用。
吴茱萸碱可能通过 TRPV1 依赖和非依赖机制发挥动脉粥样硬化保护作用和独立于肥胖的作用。
