人参皂苷 RG1 增强骨髓间充质干细胞对辐射诱导的肠损伤的旁分泌作用。

Ginsenoside RG1 enhances the paracrine effects of bone marrow-derived mesenchymal stem cells on radiation induced intestinal injury.

机构信息

Shantou University Medical College, Shantou 515041, Guangdong, P.R. China.

Department of Gastroenterology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, P.R. China.

出版信息

Aging (Albany NY). 2020 Dec 3;13(1):1132-1152. doi: 10.18632/aging.202241.

UNLABELLED

Content and aims: Ginsenoside RG1 (RG1) is thought to enhance proliferation and differentiation of stem cell, however, its role on paracrine efficacy of stem cell remains unclear. Here we examined if and how RG1 enhances the paracrine effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) on radiation induced intestinal injury (RIII).

METHOD

Irradiated rats randomly received intraperitoneal injection of conditioned medium (CM) derived from non-activated BM-MSCs (MSC-CM) or BM-MSCs pre-activated by RG-1 (RG1-MSC-CM). Intestinal samples were collected, followed by the evaluation of histological and functional change, apoptosis, proliferation, inflammation, angiogenesis and stem cell regeneration. The effects of heme oxygenase-1 (HO-1) were investigated using HO-1 inhibitor or siRNA.

RESULT

RG1 enhanced the paracrine efficacy of BM-MSCs partially through upregulation of HO-1. RG1-MSC-CM rather than MSC-CM significantly improved the survival and intestinal damage of irradiated rats via improvement of intestinal proliferation/apoptosis, inflammation, angiogenesis and stem cell regeneration in a HO-1 dependent mechanism. The mechanism for the superior paracrine efficacy of RG1-MSC-CM is related to a higher release of two pivotal cytokines VEGF and IL-6.

CONCLUSION

Our study revealed that RG1 enhances paracrine effects of BM-MSCs on RIII, providing a novel method for maximizing the paracrine potential of MSCs.

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内容和目的：人参皂苷 RG1（RG1）被认为可增强干细胞的增殖和分化，然而，其对干细胞旁分泌功效的作用尚不清楚。在这里，我们研究了 RG1 是否以及如何增强骨髓间充质干细胞（BM-MSCs）对辐射诱导的肠损伤（RIII）的旁分泌作用。

方法

受照射的大鼠随机接受腹腔内注射非激活的 BM-MSCs（MSC-CM）或经 RG-1 激活的 BM-MSCs（RG1-MSC-CM）的条件培养基（CM）。收集肠组织样本，然后评估组织学和功能变化、细胞凋亡、增殖、炎症、血管生成和干细胞再生。使用血红素加氧酶-1（HO-1）抑制剂或 siRNA 研究 HO-1 的作用。

结果

RG1 通过上调 HO-1 增强了 BM-MSCs 的旁分泌作用。与 MSC-CM 相比，RG1-MSC-CM 通过改善肠细胞增殖/凋亡、炎症、血管生成和干细胞再生，在 HO-1 依赖的机制中，显著改善了照射大鼠的生存和肠道损伤。RG1-MSC-CM 具有优越的旁分泌功效的机制与两种关键细胞因子 VEGF 和 IL-6 的更高释放有关。