| 429 | 0 | 165 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 探讨信号素3A(Sema3A)对病理性心肌肥厚进展的影响。方法 使用野生型C57BL 6J小鼠、Sema3A全身性过表达(Sema3A/Cre-ERTM)小鼠及同窝对照(Cre-ERTM)小鼠，每组6只。采用主动脉弓缩窄术(TAC)建立心肌肥厚模型，并设假手术组(Sham)作为对照。通过大体表型、心重/体质量比(HW/BW)、心重/胫骨长度比(HW/HL)和心重/肺重比(HW/PW)评估心脏肥厚程度。通过小动物超声检测射血分数(EF)和短轴缩短率(FS)评价心功能。心脏组织分别通过RT-qPCR检测心房钠尿肽(ANP)和Sema3A mRNA的表达，Western blot检测Sema3A蛋白水平，苏木精-伊红染色观察形态结构，马松染色分析纤维化程度，免疫组化检测CD31以评估血管新生。离体实验采用大鼠H9C2以血管紧张素Ⅱ(Ang Ⅱ)诱导肥大，对照组用PBS处理。48 h后通过RT-qPCR检测ANP、B型钠尿肽(BNP)及Sema3A mRNA表达，Western blot检测Sema3A蛋白水平。结果 在动物整体水平，与Sham组相比，野生型C57 BL 6J小鼠在TAC术后其心脏组织ANP的mRNA水平显著升高，Sema3A的mRNA和Sema3A蛋白水平也明显升高(均P<0.05)；与Cre-ERTM+TAC组小鼠相比，Sema3A/Cre-ERTM+TAC组小鼠心脏肥大、HW/BW、HW/HL和HW/PW及心室壁增厚均更为显著，EF及FS降低更为明显，心脏纤维化程度更为严重，心脏CD31的表达水平减少(均P<0.05)。在细胞水平，与对照组相比，H9C2细胞给予Ang Ⅱ处理后其ANP和BNP的mRNA水平升高，Sema3A的mRNA和Sema3A蛋白水平也升高(均P<0.05)。结论 Sema3A可通过抑制血管新生而促进压力负荷性心肌肥厚的进展。
Abstract：Objective To investigate the effect of Semaphorin 3A(Sema3A) on the progression of pathological cardiac hypertrophy.Methods Wild-type C57BL 6J mice, Sema3A global overexpressing(Sema3A/Cre-ERTM) mice, and their littermate controls(Cre-ERTM) were used, with 6 mice per group. A pressure-overload induced cardiac hypertrophy model was established via transverse aortic constriction(TAC), with a sham-operated group(Sham) as the control. Cardiac hypertrophy was assessed by gross morphology, heart weight/body weight ratio(HW/BW), heart weight/tibia length ratio(HW/HL), and heart weight/lung weight ratio(HW/PW). Cardiac function was evaluated by measuring ejection fraction(EF) and fractional shortening(FS) via echocardiography. In heart tissues, the mRNA level of atrial natriuretic peptide(ANP) and Sema3A were detected by RT-qPCR, Sema3A protein level was detected by western blot, morphological structure was detected by hematoxylin and eosin(HE) staining, level of fibrosis was detected by Masson's trichrome staining, and angiogenesis was detected by immunohistochemical detection of CD31. For in vitro experiments, rat H9C2 cardiomyocytes were treated with angiotensin Ⅱ(Ang Ⅱ) to induce hypertrophy, with PBS-treated cells as the control. After 48 hours, the mRNA expression of ANP, B-type natriuretic peptide(BNP) and Sema3A were measured by RT-qPCR, and Sema3A protein level was assessed by western blot.Results At the animal level, compared with the sham group, mice subjected to TAC showed significantly increased mRNA levels of ANP in cardiac tissue, as well as markedly elevated mRNA and protein levels of Sema3A(all P<0. 05). Compared with the Cre-ERTM + TAC group, the Sema3A/Cre-ERTM + TAC group exhibited more pronounced cardiac hypertrophy, greater ventricular wall thickening, higher HW/BW, HW/HL, and HW/PW ratios, more significant reductions in EF and FS, more severe cardiac fibrosis, and a significant decrease in cardiac CD31 expression levels(all P<0. 05). At the cellular level, compared with the control group, H9C2 cells treated with Ang Ⅱ displayed significantly increased mRNA levels of ANP and BNP, along with markedly elevated mRNA and protein levels of Sema3A(all P<0. 05).Conclusion Sema3A promotes the progression of pressure overload-induced cardiac hypertrophy by inhibiting angiogenesis.
[1]Tham Y K, Bernardo B C, Ooi J Y, et al. Pathophysiology of cardiac hypertrophy and heart failure:signaling pathways and novel therapeutic targets[J]. Arch Toxicol, 2015, 89(9):1401-38.doi:10. 1007/s00204-015-1477-x.
[2]Yang X, Cheng K, Wang L Y, et al. The role of endothelial cell in cardiac hypertrophy:focusing on angiogenesis and intercellular crosstalk[J]. Biomed Pharmacother,2023, 163:114799. doi:10. 1016/j. biopha. 2023. 114799.
[3]Oleari R, Lettieri A, Paganoni A, et al. Semaphorin signaling in GnRH neurons:from development to disease[J]. Neuroendocrinology, 2019, 109(3):193-9. doi:10. 1159/000495916.
[4]Koppel C J, De Henau C M S, Vreeken D, et al. The role of the axonal guidance cue semaphorin 3A in innervation of the postnatal heart in health and disease[J]. Can J Cardiol, 2025, 41(5):899-910. doi:10. 1016/j. cjca. 2024. 12. 030.
[5]Liu L N, Li X M, Ye D Q, et al. Emerging role of semaphorin-3A in autoimmune diseases[J]. Inflammopharmacology, 2018,26(3):655-65. doi:10. 1007/s10787-018-0484-y.
[6]Serini G, Valdembri D, Zanivan S, et al. Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function[J]. Nature, 2003, 424(6947):391-7. doi:10. 1038/nature01784.
[7]Vadasz Z, Toubi E. Semaphorin3A:a potential therapeutic tool in immune-mediated diseases[J]. Eur J Rheumatol, 2018, 5(1):58-61. doi:10. 5152/eurjrheum. 2017. 17076.
[8]Jiao B, Liu S, Tan X, et al. Class-3 semaphorins:potent multifunctional modulators for angiogenesis-associated diseases[J].Biomed Pharmacother, 2021, 137:111329. doi:10. 1016/j. biopha. 2021. 111329.
[9]Wu L F, Zhang J J, Zhang X, et al. Semaphorin 3A protects against thoracic aortic aneurysm dissection by suppressing aortic angiogenesis[J]. Angiogenesis, 2025, 28(3):39. doi:10. 1007/s10456-025-09992-6.
[10]张晓东，张艳涛，张磊，等.金丝桃苷在主动脉弓缩窄所致心肌肥厚中的作用[J].安徽医科大学学报，2023, 58(12):2058-63. doi:10. 19405/j. cnki. issn1000-1492. 2023. 12. 011.[10]Zhang X D, Zhang Y T, Zhang L, et al. Effect of hyperoside on transverse aortic constriction-induced cardiac hypertrophy[J].Acta Univ Med Anhui, 2023, 58(12):2058-63. doi:10. 19405/j. cnki. issn1000-1492. 2023. 12. 011.
[11]Nakamura M, Sadoshima J. Mechanisms of physiological and pathological cardiac hypertrophy[J]. Nat Rev Cardiol, 2018, 15(7):387-407. doi:10. 1038/s41569-018-0007-y.
[12]Fallah A, Sadeghinia A, Kahroba H, et al. Therapeutic targeting of angiogenesis molecular pathways in angiogenesis-dependent diseases[J]. Biomedecine Pharmacother, 2019, 110:775-85.doi:10. 1016/j. biopha. 2018. 12. 022.
[13]Patel S, Dushenkov A, Jungsuwadee P, et al. Team-based approach to management of hypertension associated with angiogenesis inhibitors[J]. J Cardiovasc Transl Res, 2020, 13(3):463-77. doi:10. 1007/s12265-020-10024-5.
[14]Wu L F, Zhou Y, Wang D P, et al. Nerve growth factor(Ngf)gene-driven semaphorin 3A(Sema3A)expression exacerbates thoracic aortic aneurysm dissection in mice[J]. J Hypertens,2024, 42(5):816-27. doi:10. 1097/HJH. 0000000000003647.
[15]Rienks M, Carai P, Bitsch N, et al. Sema3A promotes the resolution of cardiac inflammation after myocardial infarction[J]. Basic Res Cardiol, 2017, 112(4):42. doi:10. 1007/s00395-017-0630-5.
[16]Sun Y, Dong J, Chai X, et al. Semaphorin-3A alleviates cardiac hypertrophy by regulating autophagy[J]. Exp Ther Med, 2024,27(1):38. doi:10. 3892/etm. 2023. 12326.
[17]Li C, Zhao Y, Li F, et al. Semaphorin3A exacerbates cardiac microvascular rarefaction in pressure overload-induced heart disease[J]. Adv Sci(Weinh), 2023, 10(21):e2206801. doi:10. 1002/advs. 202206801.
基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2026.07.008
中图分类号:R542.2
引用信息:
[1]武栗妃,张姣姣,张星,等.信号素3A促进病理性心肌肥厚的实验研究[J].安徽医科大学学报,2026,61(07):1215-1222.DOI:10.19405/j.cnki.issn1000-1492.2026.07.008.
基金信息:
国家自然科学基金项目(编号：82170523); 山西省教育厅“1331工程”提质增效建设计划项目(编号：1331KFC); 山西省基础研究计划资助项目(编号：20210302124412、202503021211154)~~
2026-05-15
2026-05-15
2026-05-15