Exploring the protective effect and mechanism of Jisuishang Formula on rat spinal cord com-pressed neurons based on the regulation of ERS-mediated neuronal apoptosis by PERK sig-nalling pathway
Objective To observe the effects of Jisuishang Formula on the expression of mRNAs and proteins related to the PERK/eIF2α/CHOP signalling pathway in cervical spinal cord compression model rats,and to investigate the possible effect mechanisms through the regulation of ERS to inhibit neuronal apoptosis.Methods Spinal cord compression(CSM)model rats were prepared and divided into sham-operated group,model group,positive control group,and low,medium,and high dose group of Jisuishang Formula(n=8).Sa-line gavage was used in the sham-operated group and the model group,intraperitoneal injection of GSK2606414 solution was used in the positive control group,and different concentrations of Jisuishang Formula were administered in the traditional Chinese medicine group,and gavage was administered for 4 weeks consecutively.The BBB score and modified Rivlin slant board score of the rat model of cervical spinal cord compression were observed at 2 and 4 weeks after surgery;the cervical spinal cord tissues were taken at 4 weeks after surger-y,and HE staining was used to observe the histopathological changes of the model rats;the expression of CHOP and caspase3 in the tis-sues was observed by immunofluorescence;the expression levels of mRNA and protein related to the PERK/eIF2α/CHOP signalling pathway were observed by rt-qPCR and WB.mRNA and protein expression levels.Results Compared with the sham-operated group,the BBB score and modified Rivlin slant board score of the model group were reduced,the expression of CHOP and caspase3 proteins in the tissues was significantly increased,and the expression levels of mRNA and protein related to the PERK/eIF2α/CHOP signalling path-way were elevated(P＜0.05);compared with the model group,the BBB score and modified Rivlin slant board score of the positive con-trol group and the traditional Chinese medicine group were significantly increased.The BBB score and modified Rivlin slant board score of the positive control group and the Chinese medicine group were significantly higher,the protein expression of CHOP and Caspase3 in the tissues were significantly lower,and the mRNA and protein expression levels related to PERK/eIF2α/CHOP signalling pathway were lower(P＜0.05);the effect of the medium-dose group was better in the Chinese medicine intervention group(P＜0.05).Conclusion Jisuishang Formula can reduce the endoplasmic reticulum stress of cervical spinal cord neurons and apoptosis of spinal cord neurons by intervening in the PERK/eIF2α/CHOP signalling pathway,which can protect the cervical spinal cord tissues and improve the limb motor function of cervical spinal cord compression-broken rats.
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