随着新型免疫抑制剂涌现，使狼疮肾炎（LN）的炎症活动得到了有效控制，但疾病及长期激素引起的脂代谢紊乱导致血管硬化早发，成为心血管疾病的高危因素，威胁着患者的远期生存。我们前期研究证实SIRT1在P-gp介导的LN激素耐药中发挥重要作用，三七皂苷通过下调SIRT1表达逆转激素耐药。新近研究发现SIRT1和PPARγ之间存在相互作用的反馈环路，而PPARγ是脂代谢的关键靶标。因此，我们设想通过干预这一环路，起到逆转激素耐药和改善脂代谢紊乱的双重效应。本研究拟采用NZB/WF1狼疮鼠，构建siRNA及慢病毒质粒转染形成PPARγ低及高表达为对照，分别从细胞和整体水平阐明“PPARγ-SIRT1反馈环路”在激素耐药LN脂代谢紊乱中的作用，证实三七皂苷能通过调控该环路实现双重效应，为活血化瘀法提高LN整体临床疗效提供新的研究思路和科学依据。

With the new immunosuppressive drugs constantly emerging, the inflammation activity of lupus nephritis can be effectively under control.But the dyslipidemia brought by the disease lead to early atherosclerosis,which is a risk factor of cardiovascular diseases,threatening the long-time prognosis of the patients.Our preliminary study have confirmed that SIRT1 plays an important role in P-gp mediated steroid resistance,and Panax notoginseng saponins can reverse steroid resistance by downregulating SIRT1 expression.Recent studies have found that SIRT1 and PPARγ could interact with each other by "PPARγ-SIRT1 pathway",and PPARγ is a key mediator of lipid metabolism.Based on above,we assume that by intervening "PPARγ-SIRT1 pathway",we can achieve a double effect that reverse the steroid resistance in LN as well as improve their lipid metabolism.In this program,we plan to establish steroid resistance NZB/WF1 mice model of PPARγ high expression and PPARγ low expression through the transfection of siRNA and lentiviral vector plasmid,to clarify the mechanism of "PPARγ-SIRT1 pathway" in steroid resistant LN dyslipidemia at cellular and integral level,and to further confirm that panax notoginseng saponin could regulate this pathway to achieve the double effect.Hopefuuly,this program would provide us with a novel sight and scientific basis of Activating Blood Circulation TCM improving the clinical efficacy of LN.