Institute of Material Medical, School of Pharmacy, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China.
Institute of Material Medical, School of Pharmacy, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China; Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China.
Life Sci. 2016 Aug 1;158:37-45. doi: 10.1016/j.lfs.2016.06.011. Epub 2016 Jun 22.
Cardiac stem cells (CSCs)-transplanted therapy provides a promising therapy for the ischemic heart disease (IHD), especially in the epidemic of myocardial infarction (MI). The compound 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside (THSG) can induce CSC proliferation in vitro based on our previous study, so we aimed to study the induce effect of THSG on CSCs-transplanted MI rat in vivo.
Using a murine model of MI, this study was designed to evaluate the impact of THSG (30, 60, 120mg/kg) on CSCs-based therapy for MI and the underlying mechanism in this process.
The results showed that THSG on CSCs-transplanted therapy groups (THSG+CSCs groups) can significantly reduce S-T segment elevation, and increase heart rate compared with MI group. The left ventricular ejection fraction (LVEF) and the left ventricular fractional shortening (LVFS) were significantly reduced in THSG+CSCs groups compared to the MI group. The levels of enzyme expression (CK-MB, LDH), the heart weight index (HWI) and myocardial infarct size (IS) were all reduced in THSG+CSCs groups. Moreover, other changes noted during these 28days post-MI, included pathologic changes, as well as increased stem cell antigen-1 (Sca-1) expression, or expression of Nkx2.5, GATA-4, and Connexin 43 in myocardial tissue, and reduced the Caspase-3 expression.
Our findings indicated that THSG facilitated CSCs-transplanted therapy in MI. These observations may be associated with the inducted of THSG on the proliferation of CSCs in vivo and also, with the subsequent differentiation of additional intrinsic neonatal cardiomyocytes to replace damaged heart tissue.
目的：心脏干细胞（CSC）移植治疗为缺血性心脏病（IHD），特别是心肌梗死（MI）的流行提供了一种有前途的治疗方法。根据我们之前的研究，化合物 2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷（THSG）可以在体外诱导 CSC 增殖，因此我们旨在研究 THSG 在体内 MI 大鼠中对 CSC 移植的诱导作用。
使用 MI 的小鼠模型，本研究旨在评估 THSG（30、60、120mg/kg）对基于 CSC 的 MI 治疗的影响及其在该过程中的潜在机制。
结果表明，THSG 在 CSC 移植治疗组（THSG+CSCs 组）中可以显著降低 S-T 段抬高，并与 MI 组相比增加心率。与 MI 组相比，THSG+CSCs 组的左心室射血分数（LVEF）和左心室缩短分数（LVFS）明显降低。THSG+CSCs 组的酶表达（CK-MB、LDH）水平、心脏重量指数（HWI）和心肌梗死面积（IS）均降低。此外，在 MI 后 28 天内观察到的其他变化包括病理变化，以及心肌组织中干细胞抗原-1（Sca-1）表达或 Nkx2.5、GATA-4 和连接蛋白 43 表达的增加，以及 Caspase-3 表达的减少。
我们的发现表明，THSG 促进了 MI 中的 CSC 移植治疗。这些观察结果可能与 THSG 在体内诱导 CSC 增殖有关，也可能与随后分化额外的内在新生心肌细胞以替代受损的心脏组织有关。
