目的 探讨金丝桃苷通过一氧化氮合酶（NOS）/一氧化氮（NO）系统调控血管内皮影响动脉粥样硬化进程。方法 采用高脂饲料喂养ApoE^-/-小鼠复制动脉粥样硬化模型。在造模的同时给予金丝桃苷（200 mg/kg）和辛伐他汀（阳性对照，5.2 mg/kg）进行干预，每天给药2次，连续12周，每周称小鼠体质量；全血项分析仪检测小鼠血清中总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）的含量；ELISA法检测小鼠血清中丙二醛（MDA）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、NO和内皮型一氧化氮合酶（eNOS）的含量；HE染色法和油红O染色法观察小鼠胸主动脉病理学变化情况和脂质沉积状况；Western blotting检测小鼠胸主动脉中聚二磷酸腺苷核糖聚合酶1（PARP1）、精氨酸酶Ⅱ（ARG2）、eNOS和诱导型一氧化氮合酶（iNOS）蛋白的表达。结果 与模型组比较，金丝桃苷显著抑制小鼠体质量增长（P<0.05、0.01）；显著降低小鼠血清中LDL-C、MDA和IL-6的水平（P<0.05、0.01），显著升高NO和eNOS的水平（P<0.05、0.01）；显著减小小鼠主动脉管腔内斑块面积（P<0.05、0.01）并改善脂质沉积状况；显著下调小鼠主动脉组织PARP1、ARG2、iNOS的表达，并上调eNOS的表达（P<0.01）。结论 金丝桃苷可以减缓动脉粥样硬化的病理进程，可能是通过降低LDL-C水平、影响NOS活性、调节NO的合成，改善血管内皮功能实现的。

Objective To investigate hyperoside through the nitric oxide synthase (NOS)/nitrogen oxide (NO) system regulate the vascular endothelium and affect the atherosclerosis process. Methods ApoE^-/- mice were fed with high-fat diet to reproduce the atherosclerosis model. Drug intervention was given at the same time as the model for 12 weeks. The mouse growth was Monitored. The contents of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) in serum were detected by an automatic biochemical analyzer. The levels of malondialdehyde (MDA), interleukin-6 (IL-6), NO, tumor necrosis factor-α (TNF-α) and endothelial nitric oxide synthase (eNOS) were measured by ELISA. HE staining and Oil red O staining were used to observe the pathological changes and the lipid deposition in the thoracic aorta of mice. Western blotting was used to detect the expressions of poly ADP-ribose polymerase 1 (PARP1), arginase II (ARG2), eNOS and inducible nitric oxide synthase (iNOS) proteins in aorta. Results Compared with model group, hyperoside significantly inhibited the weight gain of mice (P<0.05 or 0.01). Hyperoside significantly reduced the levels of LDL-C, MDA and IL-6 in mouse serum, and increase the levels of NO and eNOS (P<0.05 or 0.01). Hyperoside could reduce the plaque area (P<0.05 or 0.01) and improve the lipid deposition in rat aortic lumen. Hyperoside significantly down-regulated the expression of PARP1, ARG2, and iNOS in mouse aortic tissue, and up-regulated the expression of eNOS (P<0.05). Conclusion Hyperoside can slow down the pathological process of atherosclerosis. It may be achieved by decreasing LDL-C level, affecting NOS activity, regulating NO synthesis and improving vascular endothelial function.

R285.5

辽宁省自然科学基金面上项目（2015010708）