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中国临床药理学与治疗学 ›› 2025, Vol. 30 ›› Issue (12): 1658-1668.doi: 10.12092/j.issn.1009-2501.2025.12.009

• 基础研究 • 上一篇    下一篇

基于转录组学探讨白连降浊方治疗脂质代谢异常的作用机理

孙嘉宁1,王瑞麒1,杨卫东1,张潞2,王艳1,程艳刚1,王颖莉3,郝旭亮2   

  1. 1山西中医药大学中药与食品工程学院,晋中  030619,山西;2山西中医药大学附属医院,太原  030024,山西;3山西中医药大学实验管理中心,晋中  030619,山西

  • 收稿日期:2025-03-26 修回日期:2025-09-16 出版日期:2025-12-26 发布日期:1900-01-01
  • 通讯作者: 郝旭亮,男,博士,教授,主任药师,硕士生导师,研究方向:中药药效物质基础及作用机制研究、中药新药及健康产品开发研究。 E-mail: hxliang-01@163.com
  • 作者简介:孙嘉宁,女,在读硕士研究生,研究方向:中药药理与毒理研究。 E-mail: 13503740883@163.com
  • 基金资助:
    山西省重点研发计划项目(202202130501012);山西省技术创新中心项目(202104010911024);山西省科技创新人才团队项目(重点)(202204051002028)

Exploring the mechanism of Bai-lian turbidity reducing formula in treating lipid metabolism disorders based on transcriptomics

SUN Jianing1, WANG Ruiqi1, YANG Weidong1, ZHANG Lu2, WANG Yan1, CHENG Yangang1, WANG Yingli3, HAO Xuliang2   

  1. 1School of Traditional Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi, China; 2Affiliated Hospital of Shanxi University of Chinese Medicine, Taiyuan 030024, Shanxi, China; 3Experimental Management Center, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi, China
  • Received:2025-03-26 Revised:2025-09-16 Online:2025-12-26 Published:1900-01-01

摘要:

目的:基于转录组学探讨白连降浊方对高脂饮食诱导的脂质代谢异常大鼠的影响。方法:取50只雄性SD大鼠,8只为空白组,剩余42只饲喂高脂饲料(HFD)进行造模,造模4周后眼眶取血测血清中的总胆固醇(TC)及甘油三酯(TG)含量变化水平以评估实验动物脂质代谢异常模型是否造模成功,剔除造模失败大鼠,将造模成功的32只大鼠随机分为4组分别为阳性药组、模型组、白连降浊方低剂量组(BLJZ-BD)、白连降浊方高剂量组(BLJZ-BG)每组8只,阳性药组给予阿托伐他汀钙片(Avt)1.25 mg/kg灌胃治疗,白连降浊方低剂量组给予白连降浊方 5 g/kg灌胃治疗,白连降浊方高剂量组给予白连降浊方10 g/kg灌胃治疗,连续给药4 周后,利用油红O染色检测肝脏组织脂质沉积现象;后对其生化指标进行检测,测量肝组织中TC、TG、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)以及丙氨酸氨基转移酶(ALT)以及天门冬氨酸氨基转移酶(AST)水平,取血清样本检测各组大鼠血清中游离脂肪酸(FFA)、脂蛋白脂肪酶(LPL)、肝酯酶(HL)以及激素敏感性甘油三酯脂肪酶(HSL)的水平;接着对大鼠肝组织利用RNAsequencing技术以确定不同生物体内的mRNA丰度并进一步筛选出显著变化的差异表达基因,并对相关的信号途径中的蛋白质活性做Western blot验证其表达。结果:油红O染色结果表明,模型组大鼠肝脏中脂质沉积面积较空白组显著升高(P<0.01),阳性药组以及白连降浊各给药组较模型组来说脂滴占比面积明显降低(P<0.01);生化指标检测结果显示,与模型组相比,阳性药组以及白连降浊方高剂量组均能明显降低脂质代谢异常大鼠肝组织中的TC、TG、LDL-C水平以及ALT、AST水平(P<0.01),升高HDL-C水平(P<0.01),均明显降低脂质代谢异常大鼠血清中FFA、HSL水平(P<0.01),显著升高LPL、HL水平(P<0.05,P<0.01)。转录组学研究表明疾病和药物的交集差异代谢物48个,核心回调基因288个,富集通路主要集中在PPAR、AMPK通路。Western blot验证结果表明白连降浊方可以上调脂质代谢异常大鼠体内的PPARα、CYP7A1以及CPT1A 蛋白表达。结论:白连降浊方可改善脂质代谢异常,其通过PPAR通路上调PPARα、CYP7A1、CPT1A 蛋白表达从而促进脂肪酸β氧化以及胆汁酸代谢过程,从而促进脂质代谢过程发挥治疗作用。

关键词: 脂质代谢异常, 白连降浊方, 转录组学, 作用机理

Abstract:

AIM: To investigate the effect of C. albido on mice with abnormal lipid metabolism induced by high-fat diet based on transcriptomics. METHODS: Fifty male SD rats were selected, with 8 designated as the blank group. The remaining 42 rats were fed a high-fat diet (HFD) for model establishment. After 4 weeks of modeling, blood samples were taken from the orbital sinus to measure changes in serum total cholesterol (TC) and triglyceride (TG) levels to assess the success of the lipid metabolism disorder model. Rats modeling failures were excluded, and the 32 successful rats were randomly divided into four groups: a positive drug group, a model group, a low-dose Bai Lian Jiang Zhuo Fang group (BLJZ-BD), and a high-dose Bai Lian Jiang Zhuo Fang group (BLJZ-BG), with 8 rats in each group. The positive drug group was treated with atorvastatin calcium tablets (Avt) at a dosage of 1.25 mg/kg via gavage, while the low-dose Bai Lian Jiang Zhuo Fang group was administered 5 g/kg by gavage, and the high-dose group received 10 g/kg by gavage. After 4 weeks of continuous administration, Oil Red O staining was utilized to detect lipid deposition in the liver tissue. Subsequent biochemical indicators were assessed, measuring TC, TG, HDL-C, LDL-C, and the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in liver tissue. Serum samples were taken to analyze levels of free fatty acids (FFA), lipoprotein lipase (LPL), hepatic triglyceride lipase (HL), and hormone-sensitive lipase (HSL) in each rat group. Additionally, RNA sequencing technology was employed on rat liver tissue to determine the mRNA abundance of different organisms and further screen significantly changed differentially expressed genes, followed by Western blotting to verify the expression of proteins in related signaling pathways. RESULTS: The results of oil red O staining showed that the area of lipid deposition in the liver of the model group was significantly higher than that of the blank group (P<0.01), and the proportion of lipid droplets in the positive drug group and the turbidity reduction group was significantly lower than that in the model group (P<0.01). The results of biochemical index analysis showed that compared with the model group, the positive drug group and the high-dose group of Bailian Turbidity Fang could significantly reduce the levels of TC, TG, LDL-C, ALT and AST in the liver tissue of rats with abnormal lipid metabolism (P<0.01), increase the levels of HDL-C (P<0.01), significantly reduce the levels of FFA and HSL in the serum of rats with abnormal lipid metabolism (P<0.01), and significantly increase the levels of LPL and HL (P<0.05, P<0.01). Transcriptomic studies showed that there were 48 differential metabolites and 288 core callback genes at the intersection of diseases and drugs, and the enrichment pathways were mainly concentrated in PPAR and AMPK pathways. Western blot verification results showed that the expression of PPARα, CYP7A1 and CPT1A proteins could be up-regulated. CONCLUSION: The anti-turbidity formula can improve the abnormal lipid metabolism, and promote the β oxidation of fatty acids and the metabolism of bile acids through the PPAR pathway, there by promoting the lipid metabolism process and playing a therapeutic role.

Key words: abnormal lipid metabolism, Bai Lian Turbidity Reducing formula, transcriptomics, mechanism of action

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