Abstract: BACKGROUND: Studies have exhibited that inhibiting apoptosis caused by endoplasmic reticulum stress can save part of nerve function. Epigallocatechin-3-gallate can inhibit endoplasmic reticulum stress, but it has poor bioavailability and is difficult to penetrate the blood-brain barrier. In combination with exosomes targeting spinal cord repair and high-potency drug loading, theoretically, the combination of the two can play a greater role in spinal cord protection. 
OBJECTIVE: To investigate the effects of epigallocatechin-3-gallate combined with bone marrow mesenchymal stem cell exosomes on endoplasmic reticulum stress and neurological function in rats with spinal cord ischemia/reperfusion injury. 
METHODS: Fifty SD male rats were randomly divided into sham surgery group, model group, epigallocatechin-3-gallate group, exosome group, and combined treatment group, with 10 rats in each group. The spinal cord ischemia/reperfusion injury model was made in the other four groups except for the sham surgery group. Local injection of physiological saline, exosomes, epigallocatechin-3-gallate, epigallocatechin-3-gallate + bone marrow mesenchymal stem cell exosomes was performed 2 hours after surgery through a caudal vein. Neurological function scores were performed on 7, 14 and 28 days after spinal cord injury. 14 days after spinal cord injury, hematoxylin-eosin staining, Nissl staining, and immunofluorescence staining of endoplasmic reticulum stress markers such as ATF6 and GADD153 were performed in the spinal cord tissues. 

RESULTS AND CONCLUSION: (1) Compared with the sham surgery group, neurological function scores of the model group, exosome group, epigallocatechin-3-gallate group and combined treatment group all decreased to different degrees. The neurological function score of combined treatment group was better than that of the epigallocatechin-3-gallate group, exosome group and model group 14 days after surgery (P < 0.05). The neurological function score of the combined treatment group was better than that of the model group and epigallocatechin-3-gallate group 28 days after surgery (P < 0.05). (2) Hematoxylin-eosin staining and Nissl staining displayed that the number of neurons in the model group decreased, with a large number of cavity necrosis and scar hyperplasia in the spinal cord injury area. The number of neurons and peripheral cavity necrosis improved to varying degrees in the epigallocatechin-3-gallate group, exosome group, and combined treatment group, with the most significant improvement in the combined treatment group. (3) The expression of endoplasmic reticulum stress-related proteins ATF6 and GADD153: 14 days postoperatively, the expression of GADD153 in the combined treatment group was lower than that in the model group and epigallocatechin-3-gallate group (P < 0.05), and the expression of ATF6 in the combined treatment group was lower than that in the model group, exosome group, and epigallocatechin-3-gallate group (P < 0.05). (4) These findings confirm that epigallocatechin-3-gallate combined with bone marrow mesenchymal stem cell exosome can enhance the neurological function in rats with spinal cord ischemia/reperfusionn injury, which may be associated with the inhibition of the expression of endoplasmic reticulum stress-related proteins ATF6 and GADD153. 

Key words: spinal cord injury, exosome, mesenchymal stem cell, epigallocatechin-3-gallate, endoplasmic reticulum stress, apoptosis