目的 探讨丹酚酸 C 通过激活 PPARα 信号通路改善 db/db 小鼠脂质代谢紊乱的作用及分子机制。 方法 将 C57BLKS/J（db/db）小鼠随机分为 5 组，每组 10 只，分别为模型组（db/db 组）、辛伐他汀组（阳性 对照药，10 mg·kg-1 ）、丹酚酸 C 低剂量组（5 mg·kg-1 ）、丹酚酸 C 中剂量组（10 mg·kg-1 ）和丹酚酸 C 高剂量组 （20 mg·kg-1 ）；另外，选取同窝 db/m 小鼠 10 只，作为正常对照组（db/m 组）。各给药组小鼠按照上述剂量灌胃 给予相应药物，每日 1 次，连续给药 8 周。检测小鼠血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固 醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）水平以及肝脏组织 TC、TG 含量。采用油红 O 染色法观察肝脏组 织中脂质蓄积情况。通过网络药理学方法筛选丹酚酸 C 干预脂质代谢紊乱的潜在作用靶点，并进行 GO 功能注 释及 KEGG 信号通路富集分析；Western Blot 法检测小鼠肝脏 PPARα、CPT1-α 及 PGC-1α 蛋白表达水平； qPCR 法检测小鼠肝脏 PPARα、ACOX1、CPT1- α、PGC-1α、SREBP-1、ACC、FABP-1、ADIPOR、ACO mRNA 表达水平；构建丹酚酸 C 干预脂质代谢紊乱的潜在作用靶点蛋白互作（PPI）网络，筛选 PPARα 通路上 游潜在核心靶点，并与丹酚酸 C 进行分子对接验证。结果 （1）动物实验研究：与正常对照组比较，模型组小 鼠的血清 TC、TG 及 LDL-C 水平均显著升高（P＜0.01），HDL-C 水平显著降低（P＜0.01）；肝脏组织可见明显 的脂质蓄积，脂滴阳性面积显著增加（P＜0.01），肝脏组织 TC、TG 水平显著升高（P＜0.01）；肝脏组织 PPARα、CPT1-α、PGC-1α 蛋白水平明显降低（P＜0.05）；肝脏组织中与脂肪酸 β-氧化、转运及线粒体转运过 程相关的 PPARα、ACOX1、CPT1-α、PGC-1α、FABP-1、ADIPOR、ACO mRNA 表达水平均显著下降（P＜ 0.01），与脂质合成相关的 SREBP-1、ACC mRNA 表达水平显著升高（P＜0.01）。与模型组比较，丹酚酸 C 中、 高剂量组小鼠的血清 TC、TG、LDL-C 水平显著降低（P＜0.05、P＜0.01），肝脏脂滴阳性面积显著减少（P＜ 0.05，P＜0.01），肝脏组织 TC、TG 水平显著降低（P＜0.01），PPARα、CPT1-α、PGC-1α、FABP-1、ACO mRNA 表达水平均显著上调（P＜0.01），ACC mRNA 表达水平显著下调（P＜0.01）；丹酚酸 C 高剂量组小鼠的血 清 HDL-C 水平明显升高（P＜0.05），肝脏组织 PPARα、CPT1-α、PGC-1α 蛋白表达水平显著升高（P＜0.01）， ACOX1、ADIPOR mRNA 表达水平显著上调（P＜0.01），SREBP-1 mRNA 表达水平显著下调（P＜0.01）。（2）网络 药理学分析：得到丹酚酸 C 干预脂质代谢紊乱的潜在作用靶点 75 个，主要参与脂肪酸代谢、类固醇代谢等脂 质代谢相关生物学过程，PPAR 信号通路可能是丹酚酸 C 调节脂质代谢的关键通路之一。筛选得到 30 个核心 靶点，丹酚酸 C 可与 PPARα 通路上游关键调控蛋白靶点 FASN、NR3C1、RXRA 稳定结合，结合能分别为-10.2、 -8.4、-8.9 kcal·mol-1 。结论 丹酚酸 C 可通过激活 PPARα 信号通路，上调其下游关键因子 CPT1-α、PGC-1α 等的表达，促进脂肪酸 β-氧化及能量代谢，抑制肝脏脂质蓄积，从而改善 db/db 小鼠脂质代谢紊乱状态。

Objective To investigate the effect and molecular mechanism of salvianolic acid C in improving lipid metabolism disorder in db/db mice by activating the PPARα signaling pathway. Methods C57BLKS/J （db/db） mice were randomly divided into 5 groups （n=10 per group）： model group （db/db group）， simvastatin group （positive control，10 mg·kg-1 ），and low-dose （5 mg·kg-1 ），medium-dose （10 mg·kg-1 ），and high-dose （20 mg·kg-1 ）salvianolic acid C groups. Additionally，10 littermate db/m mice were selected as the normal control group （db/m group）. Mice in each administration group were given the corresponding drugs by gavage once daily for 8 consecutive weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C），as well as hepatic TC and TG contents，were measured. Hepatic lipid accumulation was observed using Oil Red O staining. Network pharmacology was employed to screen potential targets of salvianolic acid C for intervening in lipid metabolism disorder，followed by GO function annotation and KEGG pathway enrichment analysis. Western Blot was used to detect the protein expression levels of PPARα，CPT1-α，and PGC-1α in mouse liver. qPCR was used to detect the mRNA expression levels of PPARα，ACOX1，CPT1-α，PGC-1α，SREBP-1， ACC，FABP-1，ADIPOR，and ACO in mouse liver. A protein-protein interaction （PPI） network of potential targets of salvianolic acid C for lipid metabolism disorder was constructed to screen upstream core targets of the PPARα pathway， and molecular docking was performed to validate the binding of salvianolic acid C with these targets. Results （1） Animai experiment： Compared with the normal control group， the model group exhibited significantly increased serum levels of TC，TG，and LDL-C （P＜0.01），and significantly decreased HDL-C levels （P＜0.01）. Marked hepatic lipid accumulation was observed，with a significant increase in the positive area of lipid droplets （P＜ 0.01） and significantly elevated hepatic TC and TG levels （P＜0.01）. Hepatic protein levels of PARα，CPT1-α，and PGC-1α were significantly decreased （P＜0.05）. The mRNA expression levels of PPARα，ACOX1，CPT1-α，PGC-1α， FABP-1，ADIPOR，and ACO，which are involved in fatty acid β-oxidation，transport，and mitochondrial transport processes， were significantly decreased （P＜0.01）， while the mRNA expression levels of lipid synthesis-related SREBP-1 and ACC were significantly increased （P＜0.01）. Compared with the model group，the medium- and highdose salvianolic acid C groups showed significantly reduced serum TC，TG，and LDL-C levels （P＜0.05，P＜0.01）， a significantly reduced positive area of hepatic lipid droplets （P＜0.05，P＜0.01），and significantly decreased hepatic TC and TG levels （P＜0.01）. The mRNA expression levels of PPARα，CPT1-α，PGC-1α，FABP-1，and ACO were significantly upregulated （P＜0.01），while ACC mRNA expression was significantly downregulated （P＜0.01）. In the high-dose salvianolic acid C group， hepatic protein expression levels of PPARα， CPT1- α， and PGC-1α were significantly increased （P＜0.01）， ACOX1，ADIPOR mRNA expression was significantly upregulated （P＜0.01）， and SREBP-1 mRNA expression was significantly downregulated （P＜0.01）.（2） Network pharamacology：A total of 75 potential targets of salvianolic acid C for intervening in lipid metabolism disorder were identified， which were primarily involved in lipid metabolism-related biological processes such as fatty acid metabolism and steroid metabolism. The PPAR signaling pathway emerged as one of the key pathways through which salvianolic acid C may regulate lipid metabolism. Thirty core targets were screened，and salvianolic acid C was shown to stably bind to the key upstream regulatory protein targets of the PPARα pathway，FASN，NR3C1，and RXRA，with binding energies of -10.2，-8.4， and -8.9 kcal·mol-1 ，respectively. Conclusion Salvianolic acid C ameliorates lipid metabolism disorder in db/db mice by activating the PPARα signaling pathway，upregulating the expression of its key downstream factors such as CPT1-α and PGC-1α， thereby promoting fatty acid β -oxidation and energy metabolism， and inhibiting hepatic lipid accumulation.

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国家自然科学基金项目（82474495，82174267）；河南省高校科技创新人才支持项目（24HASTIT072）；河南省中医药科研专项课题 （2023ZYZD15）；河南省高等学校大学生创新训练计划项目（202410471014）。