目的探讨葛根芩连汤（GQD）对动脉粥样硬化（AS）大鼠血管内皮细胞损伤及过氧化物酶体增殖物激活受体γ/肝X受体α/三磷酸腺苷结合盒转运体A1（PPARγ/LXRα/ABCA1）通路的影响。方法将SD大鼠随机分为对照组，模型组，辛伐他汀（阳性药，5 mg·kg^-1）组和GQD低、高剂量（4.1、8.2 g·kg^-1）组及GQD高剂量（8.2 g·kg^-1）＋PPARγ抑制剂（BADGE，20 mg·kg^-1，于GQD ig前30 min给予）组，每组12只，除对照组外，采用高脂饮食联合维生素D₃诱导AS大鼠模型，造模成功后每天ig给药1次，连续给药8周。检测各组血脂水平、血清炎症因子及血管内皮因子水平；苏木素-伊红（HE）染色观察主动脉内皮损伤；末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）染色观察血管内皮细胞凋亡； Western blotting法检测主动脉组织PPARγ/LXRα/ABCA1及凋亡蛋白表达。结果对照组相比，模型组主动脉病理损伤严重，有大量斑块形成，斑块损伤面积、血管内皮细胞凋亡率及血清三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、肿瘤坏死因子-α（TNF-α）、基质金属蛋白酶-9（MMP-9）、白细胞介素6（IL-6）、细胞间黏附分子-1（ICAM-1）、内皮素-1（ET-1）水平及Bcl相关蛋白X（Bax）蛋白表达显著升高（P＜0.05），血清高密度脂蛋白胆固醇（HDLC）、内皮型一氧化氮合酶（eNOS）、一氧化氮（NO）水平及PPARγ、LXRα、ABCA1、B细胞淋巴瘤-2（Bcl-2）蛋白表达显著降低（P＜0.05）；与模型组相比，辛伐他汀组和GQD低、高剂量组主动脉病理损伤减轻，斑块形成减少，斑块损伤面积、血管内皮细胞凋亡率及血清TG、TC、LDL-C、TNF-α、MMP-9、IL-6、ICAM-1、ET-1水平、Bax蛋白表达显著降低（P＜0.05），血清HDL-C、eNOS、NO水平及PPARγ、LXRα、ABCA1、Bcl-2蛋白表达显著升高（P＜0.05）；与GQD高剂量组比较，GQD＋BADGE组主动脉病理损伤严重，有大量斑块形成，斑块损伤面积、血管内皮细胞凋亡率及血清TG、TC、LDL-C、TNF-α、MMP-9、IL-6、ICAM-1、ET-1水平、Bax蛋白表达显著升高（P＜0.05），血清HDL-C、eNOS、NO水平及PPARγ、LXRα、ABCA1、Bcl-2蛋白表达显著降低（P＜0.05）。结论 GQD可能通过调控PPARγ/LXRα/ABCA1信号通路减轻AS大鼠血管内皮细胞损伤。

Objective To discuss the impacts of Gegen Qinlian decoction (GQD) on vascular endothelial cell injury and the peroxisome proliferator-activated receptor gamma/liver X receptor α/adenosine triphosphate-binding cassette transporter A1 (PPARγ/LXRα/ABCA1) pathway in rats with atherosclerosis (AS). Methods The SD rats were randomly divided into the control group, the model group, the simvastatin (positive control, 5 mg·kg^-1) group, the low and high doses of GQD (4.1 and 8.2 g·kg^-1) groups, and the high dose of GQD (8.2 g·kg^-1) + PPARγ inhibitor (BADGE, 20 mg·kg^-1, administered 30 min before GQD ig) group, with 12 rats in each group. Except for the control group, the high-fat diet combined with vitamin D₃ was used to induce the AS rat model. After successful modeling, the rats were given ig administration once a day for 8 consecutive weeks. The lipid levels, serum inflammatory factors and vascular endothelial factor levels of each group were detected; Hematoxylin-eosin (HE) staining was used to observe the aortic endothelial injury; Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to observe the apoptosis of vascular endothelial cells; Western blotting was used to detect the expression of PPARγ/LXRα/ABCA1 and apoptotic proteins in the aortic tissue. Results For the control group, the AS group had severe pathological damage to the aorta, with a large number of plaques formed. The plaque damage area, endothelial cell apoptosis rate, serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), endothelin-1 (ET-1), and the Bcl associated protein X (Bax) protein were prominently increased (P < 0.05), while the serum high-density lipoprotein cholesterol (HDL-C), endothelial nitric oxide synthase (eNOS), nitric oxide (NO) levels, and the PPARγ, LXRα, ABCA1, and B-cell lymphoma/leukemia 2 (Bcl-2) proteins were clearly reduced (P < 0.05). For the AS group, the Sim group and GQD 4.1, 8.2 g·kg^-1 group showed reduced pathological damage to the aorta, decreased plaque formation. The plaque damage area, endothelial cell apoptosis rate, serum TG, TC, LDL-C, TNF-α, MMP-9, IL-6, ICAM-1, ET-1, and the Bax protein were clearly reduced (P < 0.05), while the serum HDL-C, eNOS, NO levels, and the PPARγ, LXRα, ABCA1, Bcl-2 proteins were prominently increased (P < 0.05). For the GQD 8.2 g·kg^-1 group, the GQD+BADGE group showed severe pathological damage to the aorta, with a large number of plaques formed. The plaque damage area, endothelial cell apoptosis rate, serum TG, TC, LDL-C, TNF-α, MMP-9, IL-6, ICAM-1, ET-1, and the Bax protein were prominently increased (P < 0.05), while the serum HDL-C, eNOS, NO levels, and the PPARγ, LXRα, ABCA1, Bcl-2 proteins were prominently decreased (P < 0.05). Conclusion GQD may alleviate endothelial cell injury in AS rats by modulation PPARγ/LXRα/ABCA1 signaling pathway.

R965

河南省教育厅高等学校重点科研项目资助计划（22A320069）