基于氧化应激探讨参附注射液延缓ApoE^(-/-)小鼠动脉粥样硬化的作用及机制

An investigation of oxidative stress based effect and mechanism of Shenfu Injection on atherosclerosis of ApoE^(-/-) mice

目的探讨参附注射液对高脂喂养Apo E^(-/-)小鼠动脉粥样硬化的影响,从氧化应激角度探讨其抗动脉粥样硬化机制。方法 C57小鼠作为对照,高脂喂养Apo E^(-/-)小鼠20周后随机分为模型组、参附组,连续给药4周。测定小鼠血脂水平,ELISA法检测MPO、NOX4水平,羟胺法测定T-SOD活力,TBA法检测MDA水平;大体油红O及主动脉窦HE染色观察斑块形成;real time q PCR法检测Nrf2、Keap1 mRNA表达。结果与对照组比较,模型组TG、TC、LDL升高,HDL降低;血清SOD活性降低,MPO、NOX4和MDA含有量升高;主动脉Nrf2和Keap1 mRNA表达下调;较于与模型组比较,参附组血脂变化不明显,斑块面积减小;参附注射液干预后,抑制氧化应激水平,上调Nrf2和Keap1 mRNA表达。结论参附注射液通过激活Nrf2,干预相关酶类,进而抑制氧化应激水平抗动脉粥样硬化。

AIM To investigate the effect of Shenfu Injection on atherosclerosis（ AS） models of high-fat apolipoprotein E-deficient（ ApoE^-/-） mice,and to explore its anti-atherosclerosis mechanism through the observation of oxidative stress（ OS） variation. METHODS C57 mice were used as controls. ApoE^-/-mice fed with 20-week high fat diet were randomly divided into model group,Shenfu group for subsequent 4-week continuous corresponding intervention,after which the mice had their blood lipid levels measured,their levels of MPO and NOX4 identified by ELISA,and their T-SOD activity determined by hydroxylamine method,their MDA level detected by TBA,their plaque formation observation achieved by HE staining of aortic gross and red O of all the aorta,and their Nrf2 Mrna expression detected by real time q PCR method. RESULTS Compared with the control group,the model group manifested with increased contents of TG,TC,LDL,decreased HLD; decreased activity of SOD,increased contents of MPO,NOX4 and MDA,and down-regulated expression of aortic Nrf2 and Keap1 Mrna. Compared with the model group,Shenfu Injection group was observed with no obvious blood lipid level change,but a reduction of plaque area,and an effective inhibition on OS as revealed by improved levels of Nrf2 and Keap1 Mrna.CONCLUSION Shenfu Injection can activate Nrf2 and interfer the relevant enzymes,thus prevents the atherosclerosis progression through OS reduction.