目的 基于环磷酸腺苷（cAMP）/蛋白激酶 A（PKA）/过氧化物酶体增殖物激活受体 γ（PPARγ）通路探讨血 府逐瘀汤对动脉粥样硬化（AS）大鼠主动脉炎性损伤的影响。方法 采用高脂饲料喂养联合腹腔注射维生素D3 的方法构建动脉粥样硬化大鼠模型，造模后将动脉粥样硬化大鼠随机分为模型组、H-89组（5 mg·kg-1）、血府 逐瘀汤组（12 g·kg-1）、血府逐瘀汤+H-89组（12 g·kg-1血府逐瘀汤+5 mg·kg-1 H-89），每组12只；另取12只正常 大鼠为对照组。给药 12 周后，试剂盒检测血清血脂和炎性因子水平；油红 O 染色观察主动脉脂质沉积情况； HE 染色观察主动脉病理变化；酶联免疫吸附试验（ELISA）法检测主动脉组织中 cAMP 水平；Western Blot 法检 测大鼠主动脉组织PKA、PPARγ蛋白表达。结果 与对照组比较，模型组大鼠血清甘油三酯（TG）、总胆固醇 （TC）、低密度脂蛋白胆固醇（LDL-C）、白细胞介素6（IL-6）、白细胞介素1β（IL-1β）和肿瘤坏死因子α（TNF-α） 水平、主动脉斑块损伤比例、血管内膜-中膜厚度升高，血清高密度脂蛋白胆固醇（HDL-C）水平、主动脉组织 中cAMP水平、PKA、PPARγ蛋白水平降低（P < 0.05）；与模型组比较，血府逐瘀汤组大鼠血清TC、TG、LDL-C、 IL-6、IL-1β和TNF-α水平、主动脉斑块损伤比例、血管内膜-中膜厚度降低，血清HDL-C水平、主动脉组织 中 cAMP水平、PKA、PPARγ蛋白水平升高（P < 0.05）；H-89组上述指标呈相反变化（P < 0.05）；H-89可减弱 血府逐瘀汤对动脉粥样硬化大鼠主动脉损伤的改善作用。结论 血府逐瘀汤可能通过激活 cAMP/PKA/PPARγ 通路，改善血脂异常，抑制炎症反应，缓解动脉粥样硬化大鼠主动脉炎性损伤。

Objective To explore the effect of Xuefu Zhuyu Decoction on inflammatory injury of aorta in atherosclerotic （AS）rats based on cAMP/PKA/PPARγ pathway. Methods A high-fat diet combined with intraperitoneal injection of vitamin D3 was used to establish an AS rat model. After being modeled，AS rats were stochastically assigned into a model group，H-89 group（5 mg·kg-1），Xuefu Zhuyu Decoction group（12 g·kg-1），and Xuefu Zhuyu Decoction+H- 89 group（12 g·kg-1 Xuefu Zhuyu Decoction+5 mg·kg-1 H-89），with 12 rats in each group. Another 12 normal rats were regarded as the control group. After 12 weeks of administration，the levels of serum lipids and inflammatory factors were measured with the reagent kits. Oil red O staining was applied to observe lipid deposition in the aorta. HE staining was applied to observe pathological changes in the aorta. ELISA method was applied to detect cAMP level in aortic tissue. Western Blot was applied to detect the protein expression of PKA and PPARγ in rat aortic tissue. Results Compared with the control group，the levels of triglyceride（TC），total cholesterol（TG），low density lipoprotein cholesterol（LDL-C）， interleukin（IL）-6，IL-1β，and tumor necrosis factor-α（TNF-α）in serum，the proportion of aortic plaque injury， and the intima-media thickness in the model group were increased， while the level of high density lipoprotein cholesterol（HDL-C）in serum，cAMP level，protein levels of PKA and PPARγ in the aortic tissue were decreased （P < 0.05）. Compared with the model group，the levels of TC，TG，LDL-C，IL-6，IL-1β，and TNF-α in serum， the proportion of aortic plaque injury，and the intima-media thickness in Xuefu Zhuyu Decoction group were decreased， while HDL-C level in serum，cAMP level and protein levels of PKA and PPARγ in the aortic tissue were increased （P < 0.05）. The above indicators in the H-89 group showed opposite changes（P < 0.05）. H-89 could weaken the improvement effect of Xuefu Zhuyu Decoction on aortic injury in AS rats. Conclusion Xuefu Zhuyu Decoction may improve dyslipidemia， inhibit inflammatory response， and alleviate arterial inflammatory damage in AS rats by activating the cAMP/PKA/PPARγ pathway.

R285.5

河北省中医药管理局科研项目（2022425）