灵宝护心丹治疗动脉粥样硬化的转录组学机制研究

Transcriptomic Mechanism of Lingbao Huxin Pill for the Treatment of Atherosclerosis

目的:研究灵宝护心丹改善动脉粥样硬化的疗效和潜在作用机制。方法:C57BL/6小鼠喂以正常饮食,载脂蛋白E基因敲除(ApoE^(-/-))小鼠喂养高脂饮食诱导动脉粥样硬化模型,12周后随机分为模型组、灵宝护心丹低剂量组、灵宝护心丹中剂量组、灵宝护心丹高剂量组和他汀组。给予药物8周后,检测血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平;通过油红O染色、Masson染色、苏木素-伊红(HE)染色观察主动脉根部的病理变化。通过转录组学测序分析灵宝护心丹减轻动脉粥样硬化的机制。结果:与模型组相比,灵宝护心丹组的斑块及TC、TG、LDL-C水平明显降低,斑块的胶原面积明显增多,炎性细胞浸润减少。转录组学测序结果显示,灵宝护心丹组和模型组相比筛选出733个差异基因,富集到的通路包括脂肪酸生物合成、胶原蛋白形成、炎症信号通路等。结论:灵宝护心丹对动脉粥样硬化有显著改善作用,机制可能涉及脂质代谢和炎症反应的关键通路。

Objective:To study the therapeutic effect and potential mechanism of Lingbao Huxin Pill in improving atherosclerosis.Methods:C57BL/6 mice were fed with normal diet,and apolipoprotein E gene knockout(ApoE^(-/-))mice were fed with high-fat diet to induce the atherosclerosis model.After 12 weeks,the mice were randomly divided into model group,Lingbao Huxin Pill low-dose group,Lingbao Huxin Pill medium-dose group,Lingbao Huxin Pill high-dose group and statin group.After 8 weeks of administration,the levels of serum total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)were detected.The pathological changes of aortic root were detected by oil red O staining,Masson staining and hematoxylin-eosin(HE)staining.The mechanism of alleviating atherosclerosis of Lingbao Huxin Pill was analyzed by transcriptomic sequencing.Result:Compared with model group,the levels of plaque,TC,TG and LDL-C in the Lingbao Huxin Pill groups significantly decreased,the collagen area of plaque was significantly cells increased,and inflammatory infiltration was decreased.Transcriptomic sequencing results showed that compared with the model group,733 differential genes were screened out in the Lingbao Huxin Pill groups and the pathways enriched included fatty acid biosynthesis,collagen formation,and inflammation signaling pathways.Conclusion:Lingbao Huxin Pill could significantly improve atherosclerosis,and the mechanism might involve the key pathways of lipid metabolism and inflammatory response.