Mechanism of protective effects of Xifeng Jiejing Decoction on early brain injury in rats with subarachnoid hemorrhage based on endoplasmic reticulum stress signaling pathway
Mechanism of protective effects of Xifeng Jiejing Decoction on early brain injury in rats with subarachnoid hemorrhage based on endoplasmic reticulum stress signaling pathway
Objective To observe the effects of Xifeng Jiejing Decoction(XFJJD)on the expression of endoplasmic reticulum stress(ER stress)signaling pathway-related factors in the brain tissue of rats with early subarachnoid hemorrhage(SAH),and to explore the protective mechanism of XFJJD on early brain injury(EBI)in SAH rats.Methods A total of 168 healthy adult male SD rats were selected to establish the SAH model by intravascular puncture.After successful modeling,the rats were divided into control group(an equal volume of distilled water),sham-operated group(an equal volume of distilled water),model group(an equal volume of distilled water),nimodipine group[10 mg/(kg·d)],and low-dose XFJJD[10.8 g/(kg·d)],high-dose XFJJD group[43.2 g/(kg·d)],and nimodipine[10 mg/(kg·d)]+XFJJD group[21.6 g/(kg·d)]by random number table method,with 24 rats in each group.Each group was administered once every 12 h for 72 h continuously.The degree of neurological impairment was assessed by Garcia score;the morphology of hippocampal nerve cells was observed by HE staining;TUNEL staining was performed to determine the apoptosis of hippocampal cells in rats;Western blot was used to check the expression levels of endoplasmic reticulum stress-related markers,including glucose regulatory protein 78(GRP78),C/EBP homologous protein(CHOP),and cysteine aspartic acid specific protease-12(cysteine-12);the water content of brain tissue was calculated;EB staining was used to examine the permeability of the blood-brain barrier.Results Compared with the control group and the sham-operated group,the model group exhibited unclear hierarchical structure of the hippocampus,loose arrangement of cells in each layer,and a large number of apoptotic cells;the proportion of apoptosis of hippocampal nerve cells,the EB content and water content of the brain tissue,as well as the protein expression levels of GRP78,CHOP,and Caspase-12 in the hippocampus increased at various time points(P＜0.05),while the Garcia score decreased(P＜0.05).Compared with the model group,the low-and high-dose XFJJD groups showed clearer hippocampal tissue structure and reduced number of apoptotic cells;the proportion of apoptosis of hippocampal nerve cells,water content of brain tissue,and the protein expression levels of GRP78,CHOP,and Caspase-12 decreased at various time points(P＜0.05),while the Garcia score and EB content of brain tissue increased(P＜0.05).Conclusion Endoplasmic reticulum stress reaction occurs during the EBI process after SAH.XFJJD can reduce the expression levels of endoplasmic reticulum stress-related proteins including GRP78,CHOP,and Caspase-12,improve neurobehavioral scores of rats during EBI process,lower the water content of brain tissue,and reduce the permeability of blood-brain barrier.
维普
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