Recovery effect of PLGA microsphere-loaded VAP combined with BMMSCs on sciatic nerve injury of rats and its mechanism / 吉林大学学报(医学版)

ABSTRACT

Objective: To observe the recovery effect of polylactide-glycolic acid (PLGA) microsphere-loaded velvet antler peptide (VAP) combined with bone marrow mesenchymal stem cells (BMMSCs) on the sciatic nerve injury of the rats, and to explore the related mechanisms. Methods: The sciatic nerve injury models were made by the cross-sectional method. A total of 60 rats were randomly divided into sciatic nerve transection control group (control group), VAP group, BMMSCs transplantation (BMC) group and VAP microsphere combined with BMMSCs transplantation (VAP-BMC) group (n=15). Seven days after modeling, the rats in control group were injected with PBS solution in the transecting sciatic nerve region, the rats in VAP group were injected with PBS solution containing PLGA microspheres loading drug, the rats in BMC group were injected with PBS solution containing BMMSCs, and the rats in VAP-BMC group were injected with PBS solution containing PLGA microspheres loading drug and BMMSCs. After three months, the neurological function of the rats in various groups were evaluated by Basso, Beattie, Bresnahan (BBB) functional sports rating scale, and the morphology of sciatic nerves of the rats in various groups were detected by HE staining. The expression levels of protein disulfide isomerase (PDI), glucose regulated protein-78 (GRP-78) and Caspase-12 in sciatic nerve of the rats in various groups were detected by Western blotting method. Results; The results of BBB functional sports rating scale showed that compared with control group, the BBB scores of the rats in VAP group, BMC group and VAP-BMC group were increased (P<0. 01), especially in VAP-BMC group. The results of HE staining showed that compared with control group, the sciatic nerve fibers of the rats in VAP group, BMC group and VAP-BMC group got thicker and the diameters of axon were longer (P<0. 01). The results of Western blotting showed that compared with control group, the expression levels of PDI and Caspase-12 in the sciatic nerve of the rats in VAP group, BMC group and VAP-BMC group were significantly decreased (P<0. 01), and the expression level of GRP-78 protein in the sciatic nerve of the rats in VAP-BMC group was significantly increased (P<0. 01). Conclusion: PLGA microsphere-loaded VAP combined with BMMSCs can significantly promote the repairment of injured sciatic nerves, and its mechanism may be related to the inhibition of endoplasmic reticulum stress.