| 132 | 0 | 77 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 旨在通过转录组学与代谢组学整合分析,系统阐明四味土木香散(STP)改善腹主动脉缩窄(AAC)所致压力超负荷性心肌肥厚(CH)的作用机制。方法 采用AAC法建立心肌肥厚大鼠模型,将48只雄性SD大鼠随机分为假手术组(Sham组)、模型组(Mod组)、STP组[1.6 g/(kg·d)]和卡托普利组(CAP组)[0.015 g/(kg·d)],每组12只。连续给药8周后,评价心功能、心脏指数、组织病理及分子标志物。进一步通过转录组学与代谢组学分别筛选回调基因与代谢物,并整合两组学数据进行关联分析,以系统阐释STP的作用机制。结果 与Mod组相比,STP显著改善心功能前壁厚度(AWT)、后壁厚度(PWT)、左室射血分数(EF)和短轴缩短率(FS)(P<0.05),减轻心肌纤维化和炎症浸润,并下调心房钠尿肽(ANP)和BAX/BCL-2蛋白表达(P<0.05)。转录组学筛选出22个在Mod组vs Sham组中显著上调、STP组vs Mod组中显著下调的回调基因,代谢组学鉴定出37个回调代谢物。多组学整合分析发现STP通过回调病理性细胞增殖(纤维化)和能量代谢异常等关键进程逆转心肌肥厚。结论 STP可下调Aldh18a1表达,抑制脯氨酸合成与胶原沉积,同时改善糖酵解氧化磷酸化失衡,协同抑制心肌异常增殖、减轻纤维化并改善心功能,最终逆转压力超负荷所致的心肌肥厚。
Abstract：Objective To determine how Siwei Tumuxiang powder(STP) ameliorates pressure overload-induced cardiac hypertrophy(CH) caused by abdominal aortic constriction(AAC) through integrated transcriptomic and metabolomic analysis.Methods A CH rat model was established by inducing AAC.Forty-eight male Sprague-Dawley rats were randomly divided into four groups(n=12 per group):a sham-operation(Sham group),a model(Mod group),a STP-treatment [STP group,1.6 g/(kg·d)],and a captopril-treatment(CAP group) groups.After 8 weeks of continuous administration,cardiac function,heart weight index,histopathology,and molecular markers were evaluated.Transcriptomics and metabolomics were used to identify reversed genes and metabolites,respectively.We integrated the two omics datasets to elucidate the mechanism of STP.Results Compared with the Mod group,cardiac functional parameters,including anterior wall thickness(AWT),posterior wall thickness(PWT),ejection fraction(EF),and fractional shortening(FS) were greatly improved in the STP group(P <0.05).The myocardial fibrosis and inflammatory infiltration were also alleviated while the protein expression of atrial natriuretic peptide(ANP) and the BAX/BCL-2 ratio down-regulated(P <0.05).Transcriptomics identified 22 reversed genes that were remarkably upregulated in the Mod group vs Sham group,but downregulated in the STP group vs Mod group.Metabolomic profiling further detected 37 reversed metabolites.Integrated multi-omics showed that STP reversed CH primarily by normalizing key pathological processes,particularly aberrant cell proliferation(fibrosis) and dysregulated energy metabolism.Conclusion STP may reverse pressure overload-induced CH by downregulating Aldh18a1 expression to inhibit proline synthesis and collagen deposition,while concurrently rectifying the imbalance between glycolysis and oxidative phosphorylation.This dual action cooperatively suppresses pathological myocardial proliferation,attenuates fibrosis,and improves cardiac function.
[1]中国高血压防治指南修订委员会，高血压联盟(中国)，中国医疗保健国际交流促进会高血压病学分会，等.中国高血压防治指南(2024年修订版)[J].中华高血压杂志(中英文)，2024，32(7)：603-700.
[2]Caturano A，Vetrano E，Galiero R，et al.Cardiac hypertrophy：from pathophysiological mechanisms to heart failure development[J].Rev Cardiovasc Med，2022，23(5)：165.
[3]Ferrucci L，Fabbri E.Inflammageing：chronic inflammation in ageing，cardiovascular disease，and frailty[J].Nat Rev Cardiol，2018，15(9)：505-522.
[4]Nakamura M，Sadoshima J.Mechanisms of physiological and pathological cardiac hypertrophy[J].Nat Rev Cardiol，2018，15(7)：387-407.
[5]李克研，丁宛萱，董颖雪.中国成人肥厚型心肌病患者的猝死风险评估与预防[J].心血管病学进展，2024，45(2)：111-114，119.
[6]Na Takuathung M，Sakuludomkan W，Khatsri R，et al.Adverse effects of angiotensin-converting enzyme inhibitors in humans：a systematic review and meta-analysis of 378 randomized controlled trials[J].Int J Environ Res Public Health，2022，19(14)：8373.
[7]Kwok CS，Choy CH，Pinney J，et al.Effect of beta-blockade on mortality in patients with cardiac amyloidosis：a systematic review and meta-analysis[J].ESC Heart Fail，2024，11(6)：3901-3910.
[8]詹家国，宋少飞，杨颖溪，等.心肌肥厚中医证型和中药作用机制的现代研究进展[J].天津中医药，2023，40(6)：809-816.
[9]Liu JL，Hu JH，Tan LL，et al.Abnormalities in lysine degradation are involved in early cardiomyocyte hypertrophy development in pressure-overloaded rats[J].BMC Cardiovasc Disord，2021，21(1)：403.
[10]斯日古楞，苏宝音，高娃.蒙医辨证论治高血压病[J].中国民族医药杂志，2011，17(12)：71-72.
[11]张明发，沈雅琴.苦参碱的心脏保护作用及其机制的研究进展[J].现代药物与临床，2021，36(2)：414-420.
[12]苏龙嘎，敖力玛杨杰.蒙医学治疗过敏性鼻炎临床研究进展[J].中国民族医药杂志，2024，30(1)：76-78.
[13]蒋碧辉，魏明慧，鲁子瑜，等.基于miR-34a-5p/Notch1信号通路探讨蒙药四味土木香散对压力超负荷心肌肥厚大鼠的保护机制[J].内蒙古医科大学学报，2023，45(2)：129-133，139.
[14]Bartel J，Krumsiek J，Schramm K，et al.The human blood metabolome-transcriptome interface[J].PLOS Genet，2015，11(6)：e1005274.
[15]Currie G，Delles C.The future of “omics” in hypertension[J].Can J Cardiol，2017，33(5)：601-610.
[16]鲁子瑜，魏明慧，李健英，等.基于血清非靶向代谢组学探究四味土木香散对高血压性心肌肥厚的作用机制[J].内蒙古医科大学学报，2024，46(1)：19-23.
[17]Tang WHW，Li DY，Hazen SL.Dietary metabolism，the gut microbiome，and heart failure[J].Nat Rev Cardiol，2019，16(3)：137-154.
[18]Targher G，Byrne CD，Tilg H.MASLD：a systemic metabolic disorder with cardiovascular and malignant complications[J].Gut，2024，73(4)：691-702.
[19]Gibb AA，Hill BG.Metabolic coordination of physiological and pathological cardiac remodeling[J].Circ Res，2018，123(1)：107-128.
[20]Bai J，Liu T，Tu B，et al.Autophagy loss impedes cancer-associated fibroblast activation via downregulating proline biosynthesis[J].Autophagy，2023，19(2)：632-643.
[21]Linder SJ，Bernasocchi T，Martínez-Pastor B，et al.Inhibition of the proline metabolism rate-limiting enzyme P5CS allows proliferation of glutamine-restricted cancer cells[J].Nat Metab，2023，5(12)：2131-2147.
[22]Zhang J，Tang Y，Zhang S，et al.Mitochondrial NAD+ deficiency in vascular smooth muscle impairs collagen Ⅲturnover to trigger thoracic and abdominal aortic aneurysm[J].Nat Cardiovasc Res，2025，4(3)：275-292.
[23]Jiang Z，Lu H，Gao B，et al.Transcriptomic analysis of cardiac tissues in a rodent model of coronary microembolization[J].J Inflamm Res，2024，17：6645-6659.
[24]Rohlenova K，Goveia J，García-Caballero M，et al.Single-cell RNA sequencing maps endothelial metabolic plasticity in pathological angiogenesis[J].Cell Metab，2020，31(4)：862-877.e814.
[25]张茗，李洪伟.中医药治疗高血压左心室肥厚简况[J].实用中医内科杂志，2017，31(6)：83-85.
[26]焦露，张晨，安娜，等.中医药治疗肾性高血压研究进展[J].现代中医药，2025，45(4)：14-18.
[27]黄家昌，张孟哲，陈卿倩，等.中医药治疗高血压病的研究进展[J].中国民间疗法，2024，32(20)：109-115.
[28]齐力格尔，包欣欣，侯亚星，等.蒙药土木香四味汤的方解、化学成分、药理及临床应用研究进展[J].中国民族医药杂志，2023，29(2)：22-28.
[29]Phang JM.The regulatory mechanisms of proline and hydroxyproline metabolism：recent advances in perspective[J].Front Oncol，2022，12：1118675.
基本信息:
中图分类号:R285.5
引用信息:
[1]尹东杰,郭玉婷,任中杰,等.基于转录组与代谢组学整合分析四味土木香散改善腹主动脉缩窄诱导心肌肥厚的作用机制[J].中南药学,2026,24(06):29-37.
基金信息:
国家自然科学基金项目(No.82360095); 内蒙古自治区自然科学基金项目(No.2022LHMS08002,No.2020MS08139); 内蒙古自治区高等学校创新团队发展计划项目(No.NMGIRT2420); 内蒙古自治区科技计划项目(No.2020GG0238); 创新训练项目(No.202510132001)
2026-06-17
2026-06-17