中文摘要：

目的：研究厚朴酚对幼年自发性高血压大鼠（SHR）血压及血管胰岛素敏感性的影响并探讨其可能的机制。方法：4周龄SHR和年龄匹配的Wistar-Kyoto（WKY）大鼠各随机分为2组,分别给予厚朴酚（100 mg/kg）或蒸馏水灌胃。3周后检测其血压、血糖和血浆胰岛素;离体血管环实验检测胰岛素诱导的主动脉舒张效应;Western blotting检测过氧化物酶体增殖物活化受体γ（PPARγ）、Tribbles同源蛋白3（TRB3）表达水平以及胰岛素诱导的Akt/内皮型一氧化氮合酶（e NOS）磷酸化。体外高糖（25 mmol/L）、高脂（500μmol/L）培养人脐静脉内皮细胞（HUVECs）,厚朴酚孵育后观察PPARγ、TRB3表达水平、胰岛素诱导的Akt/e NOS磷酸化及NO的生成。结果：4周龄SHR血压尚未增高,给予厚朴酚灌胃3周后,血压增高减缓,胰岛素诱导的舒血管效应和Akt/e NOS活性增强,血管组织PPARγ表达增加,TRB3表达减少。高糖高脂培养的HUVECs厚朴酚孵育后,PPARγ表达增加,TRB3表达减少,胰岛素诱导的Akt/e NOS活性增强,NO产生增加;PPARγ拮抗剂预处理HUVECs则可阻断厚朴酚的上述效应。结论：在SHR高血压前期给予厚朴酚干预可以改善血管胰岛素敏感性,延缓血压升高,该作用部分依赖于上调血管组织PPARγ表达和减少TRB3表达,进而增强Akt和e NOS活性,提示厚朴酚有望作为一种早期抗高血压药物在高血压前期使用。

英文摘要：

AIM： To investigate the effects of magnolol（ MAG） on blood pressure and aortic vasodilatation to insulin in juvenile spontaneous hypertensive rats（ SHR）. METHODS： Four-week-old male SHR and age-matched normotensive Wistar-Kyoto（ WKY） control rats were used. SHR and WKY rats were randomized into 2 groups and treated daily by gavage with vehicle（ distilled water） or MAG（ 100 mg·kg- 1·d- 1）. After 3 weeks of treatment,blood pressure,aortic vasorelaxation,fasting glucose and plasma insulin levels,the expressions of PPARγ and TRB3,and insulin-stimulated Akt / endothelial nitric oxide synthase（ e NOS） activation were measured. In vitro,human umbilical vein endothelial cells（ HUVECs） were cultured in the medium containing glucose（ 25 mmol/L） and palmitate（ 500 μmol/L）. RESULTS：Treatment of young SHR with MAG for 3 weeks decreased blood pressure,improved insulin-induced aortic vasodilation,and Akt and e NOS activation,increased PPARγ expression and decreased TRB3 expression. In cultured HUVECs,MAG incubation increased PPARγ exprssion,decreased TRB3 expression,and elevated insulin-induced phosphorylated Akt and e NOS levels and NO production,which were reversed by PPARγ antagonist. CONCLUSION： Treatment of young SHR with MAG at the prehypertensive stage decreases blood pressure via improving vascular insulin resistance that is at least partly attributable to up-regulation of PPARγ,down-regulation of TRB3 and consequently activation of Akt and e NOS in blood vessel.