Effect of Hippocampus kelloggi on GRP-78/PERK/ATF-4 signaling pathway of endoplasmic reticulum stress response after spinal cord injury / 国际中医中药杂志

ABSTRACT

Objective:To observe the effect of Hippocampus kelloggi on GRP-78/PERK/ATF-4 signal pathway and explore its mechanism on improving spinal cord injury. Methods:A total of 36 SD rats were randomly divided into sham operation group, model group and hippocampus group with 12 rats in each group. Only laminectomy was performed in the sham operation group. The spinal cord injury model was prepared in the model group and hippocampus group. Rats in the hippocampus group were given 10 ml/kg Hippocampus kelloggi extract by gavage for 14 days. Basso Beattie Bresnahan (BBB) score was used to evaluate the motor function of the limbs. The neuron morphology was observed by Nissl staining. The expression of GRP-78, p-PERK and ATF-4 proteins were detected by Western blot, the expression of GRP-78 and ATF-4 mRNAs was detected by qPCR, Caspase-3 and Caspase-12 were detected by ELISA, and the apoptosis was detected by TUNEL. Results:Compared with the model group, the BBB score of hippocampal group increased on the 7th, 9th, 11th and 14th day after operation ( P<0.05). For hippocampus group, the relative expression of GRP-78 (0.49 ± 0.06 vs. 0.74 ± 0.03), p-PERK (0.63 ± 0.04 vs. 0.81 ± 0.06) and ATF-4 (0.51 ± 0.06 vs. 0.69 ± 0.05) protein were significantly decreased ( P<0.05), GRP-78 mRNA (0.54 ± 0.05 vs. 0.63 ± 0.06) and ATF-4 mRNA (0.61 ± 0.06 vs. 0.78 ± 0.04) were significantly decreased ( P<0.05), the content of Caspase-3 and caspase-12 were significantly decreased ( P<0.05), and the apoptosis rate of hippocampal group was significantly decreased ( P<0.05). Conclusion:Hippocampus kelloggi can regulate the stress response of the endoplasmic reticulum after spinal cord injury by inhibiting GRP-78/PERK/ATF-4 signaling pathway to promote the repair of neurons.