目的 探讨暖心康（毛冬青、红参）通过抑制内皮间充质转化 （EndMT） 减轻阻塞性睡眠呼吸暂停低通气 综合征 （OSAHS） 合并动脉粥样硬化 （AS） 小鼠斑块形成的作用及机制。方法 将雄性 ApoE-/- 小鼠随机分为 6 组： 对照组、模型组、阿托伐他汀组 （2.6 mg·kg-1 ） 以及暖心康低、中、高剂量组 （生药量 3.5、7.0、14.0 g·kg-1 ） ，每 组 8 只。采用将小鼠长期在睡眠期间暴露于慢性间歇性缺氧 （CIH） 环境，联合高脂饲料喂养，复制 OSAHS 合 并 AS 小鼠模型。采用油红 O 染色法观察小鼠主动脉内壁斑块形成情况；Masson 三色染色法评估小鼠主动脉根 部粥样斑块的胶原含量；免疫荧光法检测主动脉斑块中内皮细胞标志物 CD31 及 EndMT 标志物 Vimentin 的表 达情况；ELISA 法测定血脂水平；qPCR 法检测主动脉组织中 EndMT 标志物 α-SMA、Cdh2 mRNA 表达水平。 结果 与对照组比较，模型组小鼠的主动脉粥样斑块面积显著增加 （P＜0.01） ，主动脉根部斑块胶原沉积面积 显著增加 （P＜0.01） ；斑块处 CD31 阳性表达细胞数量显著减少 （P＜0.01） ，Vimentin 阳性表达细胞数量显著增 多 （P＜0.01） ；血清甘油三酯 （TG） 、总胆固醇 （T-CHO） 、低密度脂蛋白胆固醇 （LDL-C） 水平显著升高 （P＜ 0.01） ，高密度脂蛋白胆固醇 （HDL-C） 水平显著降低 （P＜0.01） ；主动脉组织中 α-SMA、Cdh2 mRNA 表达水平 显著升高 （P＜0.01） 。与模型组比较，暖心康各给药组的主动脉粥样斑块面积均显著减少 （P＜0.05，P＜0.01） ， 主动脉根部粥样斑块的胶原沉积面积均明显缩小 （P＜0.05，P＜0.01） ；暖心康高剂量组小鼠斑块处 CD31 阳性 表达细胞数量明显增加 （P＜0.05） ，暖心康中、高剂量组小鼠斑块处 Vimentin 阳性表达细胞数量明显减少 （P＜ 0.05，P＜0.01） ；暖心康高剂量组小鼠的血清 TG 水平显著降低 （P＜0.01） ，暖心康各给药组小鼠的血清 T-CHO、 LDL-C 水平显著降低 （P＜0.05，P＜0.01） ，暖心康中、高剂量组小鼠的血清 HDL-C 水平显著升高 （P＜0.01） ； 暖心康各给药组小鼠主动脉组织中 α-SMA、Cdh2 mRNA 表达水平显著降低 （P＜0.01） 。结论 暖心康可以有效 减轻 OSAHS 合并动脉粥样硬化小鼠的斑块形成，可能与其抑制 EndMT，减少胶原纤维形成有关。

Objective To investigate the effect and mechanism of Nuanxinkang on plaque formation in obstructive sleep apnea-hypopnea syndrome（OSAHS） comorbid with atherosclerosis（AS） mice by inhibiting endothelial-to- mesenchymal transition （EndMT）. Methods Male ApoE-/- mice were randomly divided into six groups：control group，model group，atorvastatin group （2.6 mg·kg-1 ） and Nuanxinkang low-，medium- and high- dose groups （crude drug 3.5，7.0，14.0 g·kg-1 ），with eight mice in each group. The mice were exposed to chronic intermittent hypoxia（CIH） environment during sleep for a long time，and fed with high-fat diet to replicate OSAHS comorbid with AS mouse model. Oil red O staining was used to observe the formation of plaque on aortic intima in mice. Masson trichrome staining was used to evaluate the collagen content of atherosclerotic plaques in the aortic root of mice. The expressions of endothelial cell marker CD31 and EndMT marker Vimentin in aortic plaque were detected by immunofluorescence. Blood lipid levels were determined by ELISA；the mRNA expression levels of EndMT markers α-SMA and Cdh2 in aortic tissue were detected by qPCR. Results Compared with the control group，the area of aortic atherosclerotic plaque in the model group was significantly increased （P＜0.01），and the area of collagen deposition in the aortic root plaque was significantly increased （P＜0.01）. The number of CD31 positive cells in the plaque were significantly decreased （P＜0.01）， and the number of Vimentin positive cells were significantly increased（P＜0.01）. Serum TG，T-CHO and LDL-C levels were significantly increased（P＜0.01）， and HDL-C level was significantly decreased （P＜0.01）. The mRNA expression levels of α -SMA and Cdh2 in aortic tissue were significantly increased （P＜0.01）. Compared with the model group， the area of aortic atherosclerotic plaque in Nuanxinkang groups were significantly reduced （P＜0.05，P＜0.01），and the collagen deposition area of aortic root atherosclerotic plaque were significantly reduced（P＜0.05，P＜0.01）. The number of CD31 positive expression cells in the plaque of Nuanxinkang high-dose group were significantly increased （P＜ 0.05），and the number of Vimentin positive expression cells in the plaque of Nuanxinkang medium- and high- dose groups were significantly decreased （P＜0.05，P＜0.01）. The serum TG level of mice in the high-dose group of Nuanxinkang was significantly decreased （P＜0.01）. The serum T-CHO and LDL-C levels of mice in each Nuanxinkang administration group were significantly decreased （P＜0.05，P＜0.01）. The serum HDL-C levels of mice in the medium- and high- dose groups of Nuanxinkang were significantly increased （P＜0.01）. The mRNA expression levels of α-SMA and Cdh2 in aortic tissue of mice in each treatment group were significantly decreased （P＜0.01）. Conclusion Nuanxinkang can effectively reduce the plaque formation in OSAHS comorbid with atherosclerosis mice which may be related to its inhibition of EndMT and reduction of collagen fiber formation.

R285.5

国家自然科学基金项目 （81673920）；广东省中医药管理局中医药科研项目 （20221155）