目的 探討金絲桃苷通過一氧化氮合酶（NOS）/一氧化氮（NO）系統(tǒng)調(diào)控血管內(nèi)皮影響動脈粥樣硬化進程。方法 采用高脂飼料喂養(yǎng)ApoE^-/-小鼠復(fù)制動脈粥樣硬化模型。在造模的同時給予金絲桃苷（200 mg/kg）和辛伐他?。栃詫φ?，5.2 mg/kg）進行干預(yù)，每天給藥2次，連續(xù)12周，每周稱小鼠體質(zhì)量；全血項分析儀檢測小鼠血清中總膽固醇（TC）、三酰甘油（TG）、高密度脂蛋白膽固醇（HDL-C）和低密度脂蛋白膽固醇（LDL-C）的含量；ELISA法檢測小鼠血清中丙二醛（MDA）、白細(xì)胞介素-6（IL-6）、腫瘤壞死因子-α（TNF-α）、NO和內(nèi)皮型一氧化氮合酶（eNOS）的含量；HE染色法和油紅O染色法觀察小鼠胸主動脈病理學(xué)變化情況和脂質(zhì)沉積狀況；Western blotting檢測小鼠胸主動脈中聚二磷酸腺苷核糖聚合酶1（PARP1）、精氨酸酶Ⅱ（ARG2）、eNOS和誘導(dǎo)型一氧化氮合酶（iNOS）蛋白的表達(dá)。結(jié)果 與模型組比較，金絲桃苷顯著抑制小鼠體質(zhì)量增長（P<0.05、0.01）；顯著降低小鼠血清中LDL-C、MDA和IL-6的水平（P<0.05、0.01），顯著升高NO和eNOS的水平（P<0.05、0.01）；顯著減小小鼠主動脈管腔內(nèi)斑塊面積（P<0.05、0.01）并改善脂質(zhì)沉積狀況；顯著下調(diào)小鼠主動脈組織PARP1、ARG2、iNOS的表達(dá)，并上調(diào)eNOS的表達(dá)（P<0.01）。結(jié)論 金絲桃苷可以減緩動脈粥樣硬化的病理進程，可能是通過降低LDL-C水平、影響NOS活性、調(diào)節(jié)NO的合成，改善血管內(nèi)皮功能實現(xiàn)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

遼寧省自然科學(xué)基金面上項目（2015010708）