目的 应用单细胞测序技术探索参七解毒颗粒对衰老及未明确潜能的克隆性造血（CHIP）小鼠模型心衰 后心肾功能的潜在药效机制。方法 将 10 只 C57BL/6J 年轻小鼠作为对照组，50 只 C57BL/6J 老年小鼠随机分 为模型组、参七解毒颗粒（中药）低浓度组（7.8 g·kg-1 ）、中药中浓度组（15.6 g·kg-1 ）和中药高浓度组（31.2 g·kg-1 ） 及达格列净组（10 mg·kg-1混悬液），每组 10 只，每日给药 1 次，连续给药 10 周。30 只 CD45.1 老年小鼠，随 机分为对照组、Tet2+/-移植组和 Tet2+/-移植+中药组（高浓度），每组 10 只，进行非清髓型骨髓移植（BMT）； 8 周后，植入式缓释泵皮下注射 1.5 mg·kg-1 ·min-1的血管紧张素Ⅱ，对 BMT 后的小鼠进行持续注射，对照组小 鼠则输注 PBS，4 周后开始药物治疗。给药 10 周后，使用小动物超声观察小鼠心功能变化；检测小鼠血肌酐 水平；Masson 染色法观察小鼠肾脏形态学变化及胶原纤维沉积情况；qPCR 法检测小鼠心脏、肾脏炎症和衰老 相关基因 mRNA 表达；免疫荧光法观察小鼠心脏 Collagen I、α-SMA 表达；通过单细胞转录组数据联合流式细 胞术探究参七解毒颗粒改善模型组小鼠心脏、肾脏纤维化的作用和机制。结果 与模型组比较，中药高浓度组 可改善心脏收缩和舒张功能（P＜0.000 1），心脏免疫荧光结果显示心脏 Collagen I、α-SMA 蛋白表达下降（P＜ 0.000 1），并有效改善血肌酐水平和肾脏纤维化（P＜0.000 1），降低炎症和衰老相关基因（IL-6、TNF、P21、 S100A8）mRNA 表达（P＜0.000 1）；单细胞数据拟时序分析结果发现，与对照组比较，模型组克隆性造血信号 明显升高，细胞明显向克隆性造血方向分化；与模型组比较，中药干预组克隆性造血信号明显下降，细胞向 CHIP 方向减少。 qPCR 结果表明中药干预的小鼠心脏和肾脏中的炎症因子（TNF）和衰老标记物（Spp1、 S100a8）的 mRNA 水平均明显下降（P＜0.05）。Tet2+/-骨髓原代巨噬细胞与成纤维细胞共培养免疫荧光结果显 示，中药干预后纤维化标记物水平明显降低（P＜0.000 1）。结论 参七解毒颗粒能够有效改善衰老小鼠的心肾 功能、炎症与衰老指标，并能够有效抑制与年龄相关的克隆性造血引起的免疫细胞分化导致的纤维化。

Objective To explore the potential pharmacodynamic mechanisms of the Shenqi Jiedu Granules in improving cardiac and renal function in a mouse model of heart failure induced by clonal hematopoiesis of indeterminate potential （CHIP） using single-cell sequencing technology. Methods There were 10 C57BL/6J young mice were used as control group，and 50 C57BL/6J old mice were randomly divided into model group，low- concentration group （7.8 g·kg-1 ）， medium-concentration group （15.6 g·kg-1 ）， high-concentration group （31.2 g·kg-1 ） and Dapagliflozin group （10 mg·kg-1 suspension），10 mice in each group，once a day for 10 consecutvie weeks. Thirty CD45.1 aged mice were randomly divided into control group， Tet2+/-transplantation group and Tet2+/-transplantation + Chinese medicine group （high concentration），with 10 mice in each group. Non-myeloablative bone marrow transplantation （BMT） was performed. After 8 weeks，1.5 mg·kg-1 ·min-1 angiotensin II was injected subcutaneously by osmotic pumps，and the mice after BMT were continuously injected，while the mice in the control group were infused with PBS. Drug treatment was started after 4 weeks. After 10 weeks of administration，the changes of cardiac function in mice were observed by small animal ultrasound. The serum creatinine level of mice was detected； Masson staining was used to observe the morphological changes and collagen fiber deposition in the kidney of mice. The mRNA expressions of inflammation and aging related genes in heart and kidney of mice was detected by qPCR. The expressions of Collagen I and α-SMA in mouse heart was observed by immunofluorescence. The effect and mechanism of Shenqi Jiedu Granuless on improving cardiac and renal fibrosis in model group mice were explored by single cell transcriptome data combined with flow cytometry. Results Compared with the model group， high concentration group of Shenqi Jiedu Granules improved cardiac systolic and diastolic functions （P＜0.000 1），cardiac immunofluorescence results showed a decrease in the protein expressions of cardiac Collagen I and α-SMA （P＜0.000 1），and effectively improved the blood creatinine level and renal fibrosis （P＜0.000 1），and decreased the mRNA expression of genes related to inflammation and aging （IL-6， TNF， P21， S100A8）（P＜0.000 1）. The results of Pseudotime Analysis showed that compared with the control group， the clonal hematopoietic signal in the model group was significantly increased， and the cells were significantly differentiated into clonal hematopoiesis. Compared with the model group，the clonal hematopoietic signal of the Chinese medicine intervention group decreased significantly，and the cells decreased in the direction of CHIP. The results of qPCR showed that the mRNA levels of inflammatory factors （TNF） and aging markers （Spp1，S100a8） in the heart and kidney of mice treated with Chinese medicine were significantly decreased （P＜0.05）. Immunofluorescence results of co-culture of Tet2+/-bone marrow primary macrophages and fibroblasts showed that the level of fibrosis markers was significantly reduced after Chinese medicine intervention （P＜0.000 1）. Conclusion Shenqi Jiedu Granules can effectively improve the heart and kidney function，inflammation and aging indexes of aging mice， and can effectively inhibit the fibrosis caused by immune cell differentiation caused by age-related clonal hematopoiesis.

R285.5

国家自然科学基金面上项目（82374406）；中华中医药学会青年人才托举工程项目（CACM-2021-QNRC2-B30）；广东省自然基金青年提 升项目（2023A1515030146）；广州中医药大学青年菁英人才培养“揭榜挂帅”团队项目；广州中医学院第一临床学院2023年度优秀博士学位论文 培养项目（YB202301）