目的 探讨visfatin蛋白在动脉粥样硬化（AS）病变形成中的作用，以及丹参酮ⅡA抗载脂蛋白E基因缺陷（apoE-/-）小鼠AS病变的可能机制。方法 将C57BL/6J背景的apoE-/-小鼠随机分为4组：模型组，丹参酮ⅡA高、低剂量组，阳性对照组（辛伐他汀组），每组8只。并以8只C57BL/6J小鼠作为空白对照组。apoE-/-小鼠给予高脂饮食，并按分组情况给予丹参酮ⅡA磺酸钠（20，10 mg·kg-1）或辛伐他汀（5 mg·kg-1）干预。第14周后全部处死，HE染色观察动脉斑块形成程度，测定斑块面积与管腔面积之比。酶法检测血清脂质含量。ELISA方法检测血清高敏C反应蛋白（hs-CRP）、肿瘤坏死因子-α（TNF-α）、金属基质蛋白酶-9（MMP-9）含量。采用western blotting法检测主动脉壁visfatin表达。结果 （1）空白对照组主动脉未见动脉粥样硬化改变，模型组有较明显的主动脉内膜增厚及粥样斑块的形成。模型组血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）水平及hs-CRP、TNF-α、MMP-9表达、动脉壁visfatin表达显著高于空白对照组，而高密度脂蛋白胆固醇（HDL-C）水平则显著低于空白对照组（均P＜ 0.05）。（2）与模型组比较，丹参酮ⅡA高、低剂量组、辛伐他汀组均可显著减少斑块面积与管腔面积比值，降低血脂中TC、TG、LDL-C水平（P＜ 0.05），升高HDL-C水平（P＜ 0.05）；明显降低血清细胞因子hs-CRP、TNF-α、MMP-9水平，降低小鼠主动脉壁visfatin表达。（3）在减少斑块面积、改善血脂水平、抑制炎症、抑制visfatin表达方面，丹参酮ⅡA均具有显著的剂量依赖性。丹参酮ⅡA高剂量在减少斑块面积、改善血脂水平方面与辛伐他汀差异无显著性意义，但在降低hs-CRP、TNF-α、MMP-9水平，以及下调主动脉壁visfatin表达方面显著优于辛伐他汀组。（4）apoE-/-小鼠动脉壁组织visfatin表达水平与血清hs-CRP、TNF-α、MMP-9水平具有显著的正相关关系。结论 visfatin参与了AS的发生发展，其参与机制可能与炎症机制有关。丹参酮ⅡA可能通过调节apoE-/-小鼠血脂代谢、抑制炎症细胞因子hs-CRP、TNF-α、MMP-9的表达，及下调主动脉壁visfatin表达，进而抑制apoE-/-小鼠AS病变的形成发展。

Objective To study the influence of visfatin on the development of atherosclerosis（AS），and to explore the possible anti-atherosclerotic mechanism of Tanshinone ⅡA sodium in ApoE gene knock-out mice. Methods C57BL/6J genetic background ApoE-/- mice were randomly divided into model group，high-dose Tanshinone ⅡA group（20 mg·kg-1），low-dose TanshinoneⅡA group（10 mg·kg-1），and Simvastatin group（5 mg·kg-1），8 mice in each group. Eight wild-type male C57BL/6J mice were used for blank control. ApoE-/- mice were fed with high fat diet for 14 weeks to induce AS. At the end of the experiment，the mice were executed. The aortic plaque was observed after HE dyeing，and the ratio of plaque area to arterial lumina area was calculated. The serum lipid contents were observed with enzyme method. Serum inflammation cytokines such as high-sensitivity C-reactive protein（hs-CRP），tumor necrosis factor alpha（TNF-α） and matrix metalloproteinase -9（MMP-9） were detected by enzyme-linked immunosorbent assay（ELISA）. Total protein was extracted from aortic tissue for detecting the expression of Visfatin by western blotting. Results （1）Blank control group showed no distinctive changes of atherosclerosis，model group had distinctive increase of aortic intima thickness and atherosclerotic plaque formation. Model group also had high serum levels of total cholesterol（TC），triglyceride（TG） and low-density lipoprotcin（LDL），and high inflammatory cytokines of hs-CRP，TNF-α，MMP-9，as well as high visfatin expression in aorta tissue. However，high-density lipoprotein（HDL） in the model group was lower than the black control group（P＜ 0.05）. （2）Compared with the model group，the ratio of plaque area to arterial lumina area was reduced，the serum levels of TC，TG，and LDL-C were decreased（P＜ 0.05），HDL-C was increased（P＜ 0.05），and inflammatory cytokines of hs-CRP，TNF-α，MMP-9 as well as visfatin expression were lowered in high- and low-dose TanshinoneⅡA groups and Simvastatin group.（3）TanshinoneⅡA could reduce plaque area，improve serum lipid，suppress inflammation and visfatin expression in significant dose-dependent manner. The differences in reducing plaque area and improving serum lipids between high-dose TanshinoneⅡA group and Simvastatin group were insignificant，but were significant in lowering hs-CRP，TNF-α，MMP-9 as well as visfatin expression.（4）Positive correlation was shown between visfatin expression and the levels of inflammatory cytokines of hs-CRP，TNF-α and MMP-9. Conclusion Visfatin plays a role in the development of atherosclerosis，the possible mechanism may be associated with inflammatory cytokines. TanshinoneⅡA could inhibit the development of atherosclerosis by regulating serum lipids，suppressing inflammation factors of hs-CRP，TNF-α and MMP-9，and down-regulating the expression of visfatin.

R285.5

江西省自然科学基金（20114BAB215048）。