Study on the regulatory effect of Panax notoginseng saponins combined with bone mesenchymal stem cell transplantation on IRAK1/TRAF6-NF-κB pathway in patients with diabetic cutaneous ulcers

三七总皂苷联合骨髓间充质干细胞移植对糖尿病皮肤溃疡患者IRAK1/TRAF6-NF-κB通路调控作用的研究

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作者:Yuqing Du #, Weijian Chen #, Youshan Li, Du Liang, Guobin Liu

Conclusions

PNS combined with bone mesenchymal stem cell transplantation up-regulated miR-146a-5p targeting and binding to IRAK1/TRAF6, inhibiting the activation of NF-κB pathway, which reduced the inflammatory response of DCU and facilitated the skin healing of DCU. Thus, this study provides a theoretical basis and a novel therapeutic option for the treatment of DFU with PNS combined with BMSCs.

Methods

A total of 75 SD rats were selected to make diabetic cutaneous ulcers model. According random number table method, the rats were randomly divided into a control group, a DCU group, a BMSCs group, a PNS group and BMSCs + PNS group. Five groups of rats were given without treatment. After being treated for 7 days, the rats were anesthetized with pentobarbital, and granulation tissue was collected from the central point of the wound. They were used for pathological analysis, Western blot (WB) and polymerase chain reaction (PCR) assays.

Results

The wound healing area was the largest in the BMSCs + PNS group. HE staining results showed that the PNS + BMSCs group could promote the formation of new epidermis and reduce the infiltration of inflammatory cells. Immunohistochemistry (IHC) results showed that the PNS + BMSCs group could up-regulate the expression of Ki67 protein and cell proliferation. In addition, PNS combined with BMSCs up-regulated the expression of miR-146-5p and down-regulated the expression of IL-1β, IL-6 and TNF-α, IRAK1, TRAF6 and p65 in the NF-κB signaling pathway (p < 0.05). Conclusions: PNS combined with bone mesenchymal stem cell transplantation up-regulated miR-146a-5p targeting and binding to IRAK1/TRAF6, inhibiting the activation of NF-κB pathway, which reduced the inflammatory response of DCU and facilitated the skin healing of DCU. Thus, this study provides a theoretical basis and a novel therapeutic option for the treatment of DFU with PNS combined with BMSCs.

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