前胡醇当归脂通过Slit2/ACE2调控糖尿病动脉粥样硬化中脂质紊乱的机制研究

Among the cardiovascular diseases, atherosclerosis with diabetes has high incidence and is the most serious. It is caused by dyslipidemia and can be reversed by inhibiting dyslipidemia. The western medicine therapy is short of effect on individual differences and possesses risks. Nevetheless, we have found that Decursin, one of the Chinese medicine monomer, can suppress dyslipidemia and reverse plaque in diabetic atherosclerosis mice. Moreover, Decursin can promote Slit2 and ACE2 expression and inhibite PKCθ and PKCδ activation. To illustrate the advance mechanism of how Decursin can regulate lipid, this study will be carried out from these perspectives: 1) The mechanism of how decursin can regulate Slit2/ACE2; 2) The interaction between Slit2/ACE2 and PKCδ/θ via Decursin; 3) in vivo, how Decursin can improve insulin resistance induced by dyslipidemia and reverse atherosclerosis. It is expected that the studies will provide theory evidence to how decursion, a local characteristic medicine of Yunnan province, has been applied to treat and prevent atherosclerosis with diabetes.

心血管疾病中，糖尿病动脉粥样硬化发病率高而且病变程度最为严重。而血脂紊乱是其主要病因，对抗这一病因可有效缓解动脉粥样硬化。但目前西医降脂类药物个体效果不佳，且具一定风险性。基于此，我们研究发现中药单体前胡醇当归酯（Decursin）可有效降低糖尿病动脉粥样硬化小鼠中脂质紊乱及斑块进展。而Decursin可促进Slit2及ACE2表达，并抑制PKCθ和PKCδ激活。为了更进一步阐释Decursin的调脂机制，本研究将从以下几个方面展开研究：1）Decursin调控Slit2及ACE2的机制；2）Decursin调控Slit2-ACE2与PKCδ/θ的相互作用；3）在体研究Decursin调控胰岛素抵抗引起的脂质代谢紊乱对动脉粥样硬化的作用。通过以上研究为云南特色药物当归提取物Decursin应用于糖尿病动脉粥样硬化治疗和预防提供理论依据。

心血管疾病中，糖尿病动脉粥样硬化发病率高而且病变程度最为严重。而血脂紊乱是其主要病因，对抗这一病因可有效缓解动脉粥样硬化。但目前西医降脂类药物个体效果不佳，且具一定风险性。本研究发现中药单体前胡醇当归酯（Decursin）可有效降低糖尿病动脉粥样硬化小鼠中脂质紊乱及斑块进展，前胡醇当归脂可以降低动脉粥样硬化动物模型ApoE基因敲出小鼠的血脂水平。Decursin可抑制脂质及炎症因子诱导的单核细胞向内皮细胞粘附， Decursin可抑制PKC信号通路。通过蛋白附着实验证明Decursin与PKC相互作用研究靶点。通过以上研究为云南特色药物当归提取物Decursin应用于糖尿病动脉粥样硬化治疗和预防提供理论依据。