人参皂苷 Rg1 通过 SDF-1α/CXCR4、SCF/c-kit 和 FKN/CX3CR1 轴预防大鼠血管损伤后内膜增生。
Ginsenoside Rg1 prevents vascular intimal hyperplasia involved by SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes in a rat balloon injury.
机构信息
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnocentric of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, 563000, China; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou, 550025, China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, Guizhou, 550014, China.
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnocentric of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, 563000, China; Department of Pharmacology, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, 563000, China.
出版信息
J Ethnopharmacol. 2020 Oct 5;260:113046. doi: 10.1016/j.jep.2020.113046. Epub 2020 Jun 3.
ETHNOPHARMACOLOGICAL RELEVANCE
Panax ginseng C. A. Mey. is a traditional tonic that has been used for thousands of years, and has positive effects on vascular diseases. Ginsenoside Rg1 (GS-Rg1) is one of the active ingredients of Panax ginseng C. A. Mey. and has been shown to have beneficial effects against ischemia/reperfusion injury. Our previously study has found that GS-Rg1 can mobilize bone marrow stem cells and inhibit vascular smooth muscle proliferation and phenotype transformation. However, pharmacological effects and mechanism of GS-Rg1 in inhibiting intimal hyperplasia is still unknown.
AIM OF THE STUDY
This study was aimed to investigate whether GS-Rg1 prevented vascular intimal hyperplasia, and the involvement of stromal cell-derived factor-1α (SDF-1α)/CXCR4, stem cell factor (SCF)/c-kit and fractalkine (FKN)/CX3CR1 axes.
MATERIALS AND METHODS
Rats were operated with carotid artery balloon injury. The treatment groups were injected with 4, 8 and 16 mg/kg of GS-Rg1 for 14 days. The degree of intimal hyperplasia was evaluated by histopathological examination. The expression of α-SMA (α-smooth muscle actin) and CD133 were detected by double-label immunofluorescence. Serum levels of SDF-1α, SCF and soluble FKN (sFKN) were detected by enzyme linked immunosorbent assay (ELISA). The protein expressions of SCF, SDF-1α and FKN, as well as the receptors c-kit, CXC chemokine receptor type 4 (CXCR4) and CX3C chemokine receptor type 1 (CX3CR1) were detected by immunochemistry.
RESULTS
GS-Rg1 reduced intimal hyperplasia by evidence of the values of NIA, the ratio of NIA/MA, and the ratio of NIA/IELA and the ratio of NIA/LA, especially in 16 mg/kg group. Furthermore, GS-Rg1 8 mg/kg group and 16 mg/kg group decreased the protein expressions of the SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes in neointima, meanwhile GS-Rg1 8 mg/kg group and 16 mg/kg group also attenuated the expressions of SDF-1α, SCF and sFKN in serum. In addition, the expression of α-SMA and CD133 marked smooth muscle progenitor cells (SMPCs) was decreased after GS-Rg1 treatment.
CONCLUSIONS
GS-Rg1 has a positive effect on inhibiting vascular intimal hyperplasia, and the underlying mechanism is related to inhibitory expression of SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes.
民族药理学相关性
人参 Panax ginseng C. A. Mey. 是一种传统的滋补品，已经使用了数千年，对血管疾病有积极的影响。人参皂苷 Rg1（GS-Rg1）是人参 Panax ginseng C. A. Mey. 的一种活性成分，已被证明对缺血/再灌注损伤具有有益作用。我们之前的研究发现，GS-Rg1 可以动员骨髓干细胞并抑制血管平滑肌增殖和表型转化。然而，GS-Rg1 抑制内膜增生的药理学作用和机制仍不清楚。
研究目的
本研究旨在探讨 GS-Rg1 是否可预防血管内膜增生，并探讨基质细胞衍生因子-1α（SDF-1α）/CXCR4、干细胞因子（SCF）/c-kit 和 fractalkine（FKN）/CX3CR1 轴的参与情况。
材料和方法
大鼠行颈动脉球囊损伤术。治疗组大鼠分别给予 4、8 和 16mg/kg 的 GS-Rg1 治疗 14 天。通过组织病理学检查评估内膜增生程度。通过双标免疫荧光法检测 α-SMA（α-平滑肌肌动蛋白）和 CD133 的表达。通过酶联免疫吸附试验（ELISA）检测血清 SDF-1α、SCF 和可溶性 FKN（sFKN）的水平。通过免疫化学法检测 SCF、SDF-1α 和 FKN 以及受体 c-kit、CXC 趋化因子受体 4（CXCR4）和 CX3C 趋化因子受体 1（CX3CR1）的蛋白表达。
结果
GS-Rg1 通过降低 NIA、NIA/MA、NIA/IELA 和 NIA/LA 的比值，减轻内膜增生，特别是在 16mg/kg 组。此外，GS-Rg1 8mg/kg 组和 16mg/kg 组降低了新生内膜中 SDF-1α/CXCR4、SCF/c-kit 和 FKN/CX3CR1 轴的蛋白表达，同时 GS-Rg1 8mg/kg 组和 16mg/kg 组还降低了血清中 SDF-1α、SCF 和 sFKN 的表达。此外，GS-Rg1 处理后标记平滑肌祖细胞（SMPCs）的 α-SMA 和 CD133 表达减少。
结论
GS-Rg1 对抑制血管内膜增生有积极作用，其作用机制与抑制 SDF-1α/CXCR4、SCF/c-kit 和 FKN/CX3CR1 轴的表达有关。
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