目的 探讨黄芪-当归配伍对家兔血管内膜增生、平滑肌细胞（vascular smooth muscle cells，VSMC）表型转化和增殖的影响及作用机制。方法 新西兰兔随机分为对照组、模型组、黄芪（1 g/kg）组、当归（1 g/kg）组、黄芪-当归（1∶1）组、黄芪-当归（1∶5）组、黄芪-当归（5∶1）组和阿托伐他汀（5 mg/kg）组。除对照组外，其余各组按颈总动脉套管法改良制备颈总动脉血管内膜增生模型，自术后第1天起给予2%高胆固醇饲料。各给药组于术后第1天起ig相应药物，1次/d，连续28 d。采用ELISA法检测各组家兔血清中总胆固醇（total cholesterol，TC）、三酰甘油（triglycerides，TG）、低密度脂蛋白胆固醇（low density lipoprotein cholesterol，LDL-C）和高密度脂蛋白胆固醇（high density lipoprotein cholesterol，HDL-C）水平；采用Masson染色法观察各组家兔颈动脉病理变化及血管内膜增生程度；采用免疫组化法检测各组家兔颈动脉α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）、骨桥蛋白（osteopontin，OPN）和增殖细胞核抗原（proliferating cell nuclear antigen，PCNA）表达情况；采用Western blotting法检测各组家兔颈动脉磷脂酰肌醇3-激酶（phosphatidylinositol-3-kinase，PI3K）/蛋白激酶B（protein kinase B，Akt）通路相关蛋白表达情况。结果 与对照组比较，模型组家兔血清中TC、TG、LDL-C水平显著升高（P<0.01），HDL-C水平显著降低（P<0.01）；颈动脉内膜增生明显，血管内膜面积（intimal area，IA）、内膜厚度（intimal thickness，IT）、内膜面积增生率（hyperplasia ratio of intimal area，HRIA）和内膜厚度增生率（hyperplasia ratio of intimal thickness，HRIT）均显著增加（P<0.01）；颈动脉VSMC收缩表型α-SMA表达显著降低（P<0.05），合成表型OPN和细胞增殖标志物PCNA表达增加（P<0.01）；颈总动脉p-PI3K和p-Akt蛋白表达水平显著升高（P<0.01）。与模型组比较，黄芪-当归（1∶1、5∶1）组家兔血清中TC、TG和LDL-C水平显著降低（P<0.05、0.01），HDL-C水平显著升高（P<0.01）；当归组血清中TG和LDL-C水平显著降低（P<0.05、0.01）；黄芪-当归（1∶1、5∶1）组家兔颈动脉IA、IT、HRIA、HRIT均显著降低（P<0.01），颈总动脉α-SMA表达显著升高（P<0.05、0.01），OPN和PCNA表达显著降低（P<0.01）；黄芪-当归（1∶5）组颈总动脉PCNA表达显著降低（P<0.01）；黄芪-当归（1∶1、1∶5、5∶1）组颈总动脉p-PI3K和p-Akt蛋白表达水平显著降低（P<0.05、0.01）。结论 黄芪-当归（1∶1、5∶1）能够有效改善家兔血管内膜增生、调节血脂、调控VSMC表型转化和增殖，其作用机制与抑制PI3K/Akt信号通路有关。

Objective To explore the effect and mechanism of Huangqi (Astragali Radix)-Danggui (Angelicae Sinensis Radix) on intimal hyperplasia, phenotypic transformation and proliferation of vascular smooth muscle cells (VSMC) in rabbits. Methods New Zealand rabbits were randomly divided into control group, model group, Astragali Radix (1 g/kg) group, Angelicae Sinensis Radix (1 g/kg) group, Astragali Radix-Angelicae Sinensis Radix (1:1, 1:5, 5:1) groups and atorvastatin (5 mg/kg) group. Except for control group, the other groups were modified to prepare the intimal hyperplasia model of common carotid artery according to common carotid artery cannula method, and given 2% high-cholesterol diet from the first day after operation. Rabbits in each administration group were ig corresponding drugs on the first day after surgery, once a day for 28 d. ELISA was used to detect levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in serum of rabbits in each group; Masson staining method was used to observe the pathological changes of carotid artery and degree of vascular intimal hyperplasia in rabbits of each group; Immunohistochemical method was used to detect the expressions of α-smooth muscle actin (α-SMA), osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) in carotid artery of rabbits in each group; Western blotting was used to detect the expressions of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway related proteins in carotid arteries of rabbits in each group. Results Compared with control group, the levels of TC, TG and LDL-C in serum of rabbits in model group were significantly increased (P < 0.01), and HDL-C level was significantly decreased (P < 0.01); Carotid artery intimal hyperplasia was obvious, intimal area (IA), intimal thickness (IT), hyperplasia ratio of intimal area (HRIA) and hyperplasia ratio of intimal thickness (HRIT) in endovascular were significantly increased (P < 0.01); Expression of VSMC contraction phenotype α-SMA was significantly reduced (P < 0.05), expressions of synthetic phenotype OPN and cell proliferation marker PCNA in carotid artery were increased (P < 0.01); Expressions of p-PI3K and p-Akt in common carotid artery were significantly increased (P < 0.01). Compared with model group, the levels of TC, TG and LDL-C in serum of rabbits in Astragali Radix-Angelicae Sinensis Radix (1:1, 5:1) groups were significantly reduced (P < 0.05, 0.01), and HDL-C level was significantly increased (P < 0.01); Levels of TG and LDL-C in serum of rabbits in Angelicae Sinensis Radix group were significantly reduced (P < 0.05, 0.01); IA, IT, HRIA and HRIT in carotid of rabbits in Astragali Radix-Angelicae Sinensis Radix (1:1, 5:1) groups were significantly reduced (P < 0.01), α-SMA expression in carotid artery of rabbits were significantly increased (P < 0.05, 0.01), OPN and PCNA expressions were significantly decreased (P < 0.01); PCNA expression in carotid artery of rabbits in Astragali Radix-Angelicae Sinensis Radix (1:5) was significantly reduced (P < 0.01); Expressions of p-PI3K and p-Akt in common carotid artery of rabbits in Astragali Radix-Angelicae Sinensis Radix (1:1, 1:5, 5:1) groups were significantly decreased (P < 0.05, 0.01). Conclusion Astragali Radix-Angelicae Sinensis Radix (1:1, 5:1) can effectively improve intimal hyperplasia of vascular in rabbits, regulate blood lipids, regulate VSMC phenotypic transformation and proliferation, and its mechanism is related to the inhibition of PI3K/Akt signaling pathway.

R285.5

国家自然科学基金资助项目（81874406）；湖南中医药大学研究生创新课题（2019CX01）；湖南中医医药大学中西医结合一流学科开放基金资助项目（2019ZXYJH10）