[Animal Modeling] Experimental Study on the Effect of MTS1/2 Inhibitor on the Repair of Spinal Cord Injury in Rats

  Objective To investigate the effects of MST1/2 inhibitors on the expression of Yes related protein YAP, nerve growth related protein 43, glial fibrillary protein GFAP, apoptosis factor Caspase 3, and motor function recovery after spinal cord injury in rats.

  Methods 105 adult female SD rats weighing 180 to 200 g were selected, and 35 rats underwent laminectomy without drug injection as a sham operation group. 70 rats were divided into two groups: normal saline group and MST1/2 inhibitor group. Normal saline and 1 mg/kg XMU-MP-1 were injected intraperitoneally. On the 1st, 3rd, 7th, 14th, 21st, and 28th days after surgery, oblique plate test and BBB motor function score were performed, and then the rats were killed to collect tissues around the spinal cord injury area. Immunofluorescence staining and immunoblotting were performed to observe the changes in the expression of YAP, GAP43, Caspase3, and GFAP in the spinal cord tissues of rats in each group.

  Results The results of oblique plate test and BBB motor function score showed that from the 7th day after surgery, the score of MST1/2 inhibitor group was significantly higher than that of normal saline group, lasting until the 28th day after surgery, with a statistically significant difference (P<0. 05) 05)。 Immunoblotting results showed that the expression of YAP in the MST1/2 inhibitor group was significantly higher than that in the saline group on the 14th day after surgery, with a statistically significant difference (P<0. 05) 05); On the 14th day after surgery, the expression of GFAP and Caspase3 in the MST1/2 inhibitor group was significantly lower than that in the saline group, and the expression of GAP43 was found, with a statistically significant difference (P<0. 05) 05)。 Fluorescence staining showed that the MST1/2 inhibitor group had less inflammatory cell infiltration and formed a neural tissue structural framework, while the saline group had significant inflammatory cell infiltration and formed a large number of glial scars. The results of immunofluorescence staining showed that YAP was expressed in neural cells in the sham operation group, while YAP was expressed in glial cells in the normal saline group and the MST1/2 inhibitor group. The number of YAP and GAP43 positive cells in the MST1/2 inhibitor group was significantly higher than that in the other two groups. The number of mature and hypertrophic astrocytes in the MST1/2 inhibitor group was significantly lower than that in the normal saline group; Immunofluorescence double labeling results showed that there was co expression of YAP and GFAP.

  Conclusion After spinal cord injury, high-dose administration of MST1/2 inhibitors can significantly promote the expression of YAP, alleviate inflammatory injury reactions, inhibit neuronal apoptosis, improve the microenvironment of the spinal cord injury area, promote the formation of primitive neural tissue structural framework by astrocytes, facilitate the regeneration and repair of neural processes, and promote the recovery of motor function.