Background

Mesenchymal stem cells (MSCs) and Salvianolic acid B (SAB) are known to exert potent anti-inflammatory and anti-oxidative properties. But the effect of SAB and MSCs combination treatment on the cerebral ischemia/reperfusion injury (CI/RI) is not clear.

Methods

After the CI/RI animal model established, rats were administered with MSCs and SAB individually or combination treatment. To evaluate the therapeutic potential, behavioral tests, TTC staining, Hematoxylin-eosin (HE) staining, and immunofluorescence assays were performed to evaluate the neuroprotection and endogenous neurogenesis. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and enzyme linked immunosorbent assay (ELISA) were performed to evaluate the anti-apoptosis and anti-inflammatory effect. Meanwhile, the expression of the TLR4/NF-ĸB/MYD88 signal pathway-related proteins was evaluated by Western blot.

Results

MSCs and SAB individually or combination treatment have protective effect in CI/RI rats. More importantly, the rats with the combination treatment showed a better behavioral recovery, neurogenesis and smaller infarct size compared with the rats administered with MSCs or SAB individually. Further research showed that the combination treatment decreased CI/RI induced inflammatory cytokines and oxidative stress, including inhibiting the production of IL-1β, IL-6, TNF-α, decreasing the levels of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD). In addition, the neuroprotection effect of SAB and MSCs combination was achieved through the regulation of TLR4/NF-κB/MyD88 signaling pathway related proteins, including inhibition the protein levels of TLR4, MYD88, p-NF-κB p65, TRAF6-and action of SIRT1 in brain tissues.

Conclusion

The present study indicated that the MSCs and SAB combination treatment had better protective effect against rat ischemic brain injury. The combination of SAB and MSCs may provide a potent and promising strategy for the treatment of ischemic stroke and is worthy for further development.

中文翻译：

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丹酚酸B联合间充质干细胞抗大鼠缺血性脑损伤的潜在作用

背景

已知间充质干细胞 (MSC) 和丹酚酸 B (SAB) 具有有效的抗炎和抗氧化特性。但SAB和MSCs联合治疗对脑缺血/再灌注损伤(CI/RI)的影响尚不清楚。

方法

CI/RI动物模型建立后，给予大鼠MSCs和SAB单独或联合治疗。为了评估治疗潜力，进行了行为测试、TTC 染色、苏木精-伊红 (HE) 染色和免疫荧光测定，以评估神经保护和内源性神经发生。采用末端脱氧核苷酸转移酶 dUTP 缺口末端标记 (TUNEL) 染色和酶联免疫吸附测定 (ELISA) 来评估抗凋亡和抗炎作用。同时，通过Western blot检测TLR4/NF-ĸB/MYD88信号通路相关蛋白的表达。

结果

MSCs和SAB单独或联合治疗对CI/RI大鼠具有保护作用。更重要的是，与单独施用 MSC 或 SAB 的大鼠相比，联合治疗的大鼠表现出更好的行为恢复、神经发生和更小的梗塞面积。进一步研究表明，联合治疗可减少 CI/RI 诱导的炎症细胞因子和氧化应激，包括抑制 IL-1β、IL-6、TNF-α 的产生，降低丙二醛 (MDA) 水平，并增加超氧化物活性歧化酶（SOD）。此外，SAB与MSCs联合的神经保护作用是通过调节TLR4/NF-κB/MyD88信号通路相关蛋白来实现的，包括抑制TLR4、 MYD88 、p-NF-κB p65、TRAF6的蛋白水平和作用SIRT1 在脑组织中的表达。

结论

本研究表明MSCs与SAB联合治疗对大鼠缺血性脑损伤具有较好的保护作用。SAB和MSC的联合可能为治疗缺血性中风提供有效且有前景的策略，值得进一步开发。