白藜芦醇通过调节 iNOS 抑制 C57BL／6J小鼠动脉粥样硬化的机制探讨

摘要

目的：探讨白藜芦醇（ resveratrol ， RES ）对卵巢切除小鼠血脂四项总胆固醇（ CHOL ）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL－C）、高密度脂蛋白胆固醇（HDL－C）以及血清一氧化氮（nitric oxide，NO）含量、胸主动脉的过氧亚硝基阴离子（peroxynitrite anion，ONOO－）及诱导型一氧化氮合酶（inducible nitric oxide synthase，iN－OS）蛋白表达水平的影响。方法：雌性C57小鼠经卵巢切除建立去势模型后，分为假手术组、单纯去势组、假手术高脂组、模型高脂组和RES组。单纯去势组和假手术组给予普通饲料，其余给予高脂饲料。14周后，收集血清检测各组血清的CHOL、TG、LDL－C和HDL－C水平，硝酸还原酶法测血浆NO水平，油红O染色观察动脉粥样硬化（ atherosclerosis ，AS）情况，DAB染色测定血管ONOO－及iNOS水平，免疫印迹测定血管组织的iNOS表达。结果：模型高脂组血清CHOL、TG、LDL－C和NO较正常对照组升高（P＜0．05）；与模型高脂组相比，RES组可降低小鼠血清的TC、TG、LDL－C和NO（ P＜0．05）；14周后，AS模型成功建立，模型高脂组有明显的AS病理改变，单纯去势组无明显AS斑块，RES组AS病变明显减轻；高脂喂养14周后，模型高脂组血管组织的iNOS及ONOO–表达也较正常对照组明显提高（P＜0．05）；与模型高脂组相比，RES组可降低小鼠胸主动脉的iNOS表达（P＜0．05），与此同时，血管ONOO－含量较模型高脂组降低。结论：RES可以抑制iNOS表达，减少NO生成，防治动脉粥样硬化。%AIM:To investigate the effect of resveratrol on the lipids ( CHOL, TG, LDL-C and HDL-C) , ni-tric oxide ( NO) , peroxynitrite anion ( ONOO-) and the expression of inducible nitric oxide synthase ( iNOS) in the artery of the mice with ovariotomy ( OVX) .METHODS:The lipid levels and NO level in the serum were measured .The chan-ges of atherosclerosis were evaluated with Oil Red O staining .The expression of iNOS was measured by DAB staining and Western blot .The ONOO-production was measured by DAB staining .RESULTS:Compared with sham group , the levels of the lipids and NO production in OVX +high fat (HF) group were increased (P<0.05).Compared with OVX+HF group, the levels of the lipids and NO production in resveratrol group were decreased (P<0.05).Fourteen weeks later, the atherosclerosis model was successfully established .Compared with OVX +HF group, the iNOS expression and the ONOO-production in resveratrol group were decreased ( P<0.05 ) , while those in sham group were increased ( P <0.05).CONCLUSION:Resveratrol prevents and treats atherosclerosis by inhibiting the iNOS expression in C 57BL/6J mice.