Han Yong-Li, Jin Shu-Wen, Pan Xiao-Li, Zhang Hong-Xing
Acupuncture Department, The First Affiliated Hospital of Henan University of CM, Zhengzhou, Henan, 450003, China.
Department of Acupuncture and Rehabilitation, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, 310007, China.
J Tradit Complement Med. 2024 Oct 30;15(4):423-433. doi: 10.1016/j.jtcme.2024.10.003. eCollection 2025 Jul.
Electroacupuncture (EA) is an effective treatment for hyperlipidemia because it decreases the protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and liver X receptor alpha (LXRα). Lowering blood lipids can reverse cardiac insufficiency, but the underlying mechanisms remain unclear. We aimed to explore whether EA reduces blood lipid levels and restores cardiac function in hyperlipidemic rats and to elucidate the underlying mechanism involved.
A hyperlipidemic rat model was established by providing the animals with a high-fat diet (HFD). Animals were divided into normal control diet (NC), HFD, PPARγ siRNA, EA, and EA + PPARγ siRNA groups. H&E staining was used to observe the histopathology of the heart and liver. Transmission electron microscopy and oil red O staining were used to detect the distribution of myocardial lipid droplets and the efferocytosis of macrophages. Double immunofluorescence was used to detect the expression of ATP binding cassette transport A1 (ABCA1), ATP binding cassette transport G1 (ABCG1), PPARγ, LXR, and MER proto-oncogene tyrosine kinase (MerTK) in cardiac macrophages. The MerTK-/- rats and littermate wild-type rats were divided into NC, HFD, and EA groups. The efferocytosis rate of myocardial macrophages in different groups was detected using TUNEL and Annexin V-FITC/PI double staining.
EA had positive effects on the blood lipid profile, cardiac function, and heart and liver weights; reduced fat deposition in cardiomyocytes and hepatocytes; promoted reverse cholesterol transport; and enhanced macrophage efferocytosis in HFD-fed rats. This effect was blocked by PPARγ siRNA. The protein expression of the PPARγ-LXRα-MerTK pathway was also increased by EA treatment. However, under MerTK-/- conditions, the beneficial effects of EA on efferocytosis in myocardial macrophages were blocked. EA reversed ectopic lipid deposition in the liver and heart, increased efferocytosis in myocardial macrophages, improved hyperlipidemia, and ameliorated cardiac dysfunction in HFD-fed rats through the PPARγ-LXRα-MerTK pathway.
电针是治疗高脂血症的有效方法，因为它可降低过氧化物酶体增殖物激活受体γ（PPARγ）和肝X受体α（LXRα）的蛋白表达。降低血脂可逆转心脏功能不全，但其潜在机制尚不清楚。我们旨在探讨电针是否能降低高脂血症大鼠的血脂水平并恢复心脏功能，并阐明其中的潜在机制。
通过给动物喂食高脂饮食（HFD）建立高脂血症大鼠模型。将动物分为正常对照饮食（NC）组、HFD组、PPARγ小干扰RNA（siRNA）组、电针组和电针 + PPARγ siRNA组。采用苏木精-伊红（H&E）染色观察心脏和肝脏的组织病理学变化。利用透射电子显微镜和油红O染色检测心肌脂质小滴的分布及巨噬细胞的胞葬作用。采用双重免疫荧光法检测心脏巨噬细胞中ATP结合盒转运蛋白A1（ABCA1）、ATP结合盒转运蛋白G1（ABCG1）、PPARγ、LXR和MER原癌基因酪氨酸激酶（MerTK）的表达。将MerTK基因敲除（MerTK-/-）大鼠和同窝野生型大鼠分为NC组、HFD组和电针组。采用末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）法和膜联蛋白V-异硫氰酸荧光素/碘化丙啶（Annexin V-FITC/PI）双重染色检测不同组中心肌巨噬细胞的胞葬作用率。
电针可改善高脂血症大鼠的血脂谱、心脏功能以及心脏和肝脏重量；减少心肌细胞和肝细胞中的脂肪沉积；促进胆固醇逆向转运；增强巨噬细胞的胞葬作用。PPARγ siRNA可阻断这一效应。电针治疗还可增加PPARγ-LXRα-MerTK通路的蛋白表达。然而，在MerTK基因敲除的情况下，电针对心肌巨噬细胞胞葬作用的有益影响被阻断。电针通过PPARγ-LXRα-MerTK通路逆转了肝脏和心脏的异位脂质沉积，增加了心肌巨噬细胞的胞葬作用，改善了高脂血症，并减轻了高脂饮食喂养大鼠的心脏功能障碍。
