Rong Yi, Wu Qian, Tang Jingjing, Liu Zhiguo, Lv Qianyu, Ye Xuejiao, Dong Yu, Zhang Yuebo, Li Guangxi, Wang Shihan
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Evid Based Complement Alternat Med. 2022 Oct 15;2022:4463108. doi: 10.1155/2022/4463108. eCollection 2022.
Danlou tablet (DLT), the traditional Chinese medicine has been commonly used for dyslipidemia, atherosclerosis, and coronary heart disease. Whether it was effective against vascular injury caused by CIH has remained unknown. The aim of the current study was to observe the effects of DLT on chronic intermittent hypoxia (CIH)-induced vascular injury via regulation of blood lipids and to explore potential mechanisms.
Sixteen 12-week-old male ApoE mice were randomly divided into four groups. The sham group was exposed to normal room air, whereas the other three groups were exposed to CIH. Mice in the CIH + normal saline (NS) group were gavaged with NS. Mice in the CIH + Angptl4-ab group were intraperitoneally injected with Angptl4-antibody. Mice in the CIH + DLT group were gavaged with DLT. After four weeks of intervention, serum lipid concentrations, and serum lipoprotein lipase (LPL) activity were detected. The changes in atherosclerosis in vascular tissue were detected by hematoxylin and eosin (H&E) staining. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were applied to detect the expression levels of hypoxia-induciblefactor-1 (HIF-1), factor-inhibiting HIF-1 (FIH-1), angiopoietin-like 4 (Angptl4), and LPL in different tissues.
CIH exposure increases serum lipid levels, decreases serum LPL activity, and exacerbates atherosclerosis. Both Angptl4-ab and DLT treatment reversed the changes in lipid concentration, LPL activity, and atherosclerosis caused by CIH. In the epididymal fat pad, CIH exposure decreased the expression of FIH-1 and increased the expression of HIF-1, whereas DLT treatment increased the expression of FIH-1 and LPL and inhibited the expression of HIF-1 and Angptl4. In heart tissue, the expression levels of LPL and Angptl4 were not affected by modeling or treatment.
DLT improved vascular damage by improving the increase in blood lipids induced by CIH, potentially by upregulating FIH-1 and downregulating HIF-1 and Angptl4 in adipose tissue. Therefore, DLT may be a promising agent for the prevention and treatment of CIH-induced vascular injury.
丹蒌片（DLT）作为一种传统中药，常用于治疗血脂异常、动脉粥样硬化和冠心病。其对慢性间歇性缺氧（CIH）所致血管损伤是否有效尚不清楚。本研究旨在观察丹蒌片通过调节血脂对CIH诱导的血管损伤的影响，并探讨其潜在机制。
将16只12周龄雄性载脂蛋白E（ApoE）小鼠随机分为四组。假手术组暴露于正常室内空气，其他三组暴露于CIH环境。CIH + 生理盐水（NS）组小鼠灌胃给予NS。CIH + Angptl4抗体组小鼠腹腔注射Angptl4抗体。CIH + DLT组小鼠灌胃给予DLT。干预四周后，检测血清脂质浓度和血清脂蛋白脂肪酶（LPL）活性。通过苏木精-伊红（H&E）染色检测血管组织中动脉粥样硬化的变化。应用定量实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹分析检测不同组织中缺氧诱导因子-1（HIF-1）、抑制HIF-1因子（FIH-1）、血管生成素样4（Angptl4）和LPL的表达水平。
暴露于CIH会增加血清脂质水平，降低血清LPL活性，并加重动脉粥样硬化。Angptl4抗体和DLT治疗均可逆转CIH引起的脂质浓度、LPL活性和动脉粥样硬化的变化。在附睾脂肪垫中，CIH暴露降低了FIH-1的表达，增加了HIF-1的表达，而DLT治疗增加了FIH-1和LPL的表达，并抑制了HIF-1和Angptl4的表达。在心脏组织中，LPL和Angptl4的表达水平不受建模或治疗的影响。
丹蒌片通过改善CIH诱导的血脂升高来改善血管损伤，可能是通过上调脂肪组织中的FIH-1并下调HIF-1和Angptl4实现的。因此，丹蒌片可能是预防和治疗CIH诱导的血管损伤的一种有前景的药物。
