To Investigate the Protective Effect and Mechanism of Siwei Huangqi Powder on Rats with High-altitude Hypoxia-induced Brain Injury Based on PERK/eIF2α/ATF4/CHOP Signaling Pathway
Objective To investigate the protective effect of Siwei Huangqi Powder (Astragalus tibeticola Podlech,Croci Stigma,Chuangxiong Rhizoma,Aquilariae Lignum Resinatum) on rats with high-altitude hypoxia-induced brain injury based on the protein kinase R-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2α (eIF2α)/transcription activator 4 (ATF4)/endoplasmic reticulum stress enhancer binding (C/EBP) homologous protein (CHOP) signaling pathway. Methods SD rats were randomly divided into blank group,model group,the high-,medium-and low-dose of Siwei Huangqi Powder groups(3.255,6.510,13.020 g·kg-1·d-1)and positive drug group (Nuodikang,0.125 g·kg-1·d-1),with 10 rats in each group. Each dose group of Siwei Huangqi Powder was administered by gavage,once a day for 14 days. The rats in the positive drug group were given Nuodikang by gavage,once a day for seven days. A rat model of plateau hypoxic brain injury was replicated in a low-pressure simulation chamber,hypoxic exposure for seven days. HE staining was used to observe pathological changes in rat brain tissue. TdT-mediated dUTP nick end-labeling(TUNEL)staining was used to detect the apoptosis of brain cells. The contents of malondialdehyde (MDA) and glutathione (GSH) in brain tissue were detected by TBA and microplate method,respectively. The protein expressions of p-PERK/PERK,p-eIF2α/eIF2α,ATF4 and CHOP in brain tissue were detected by Western Blot. RT-qPCR was used to detect the mRNA expression of PERK,eIF2α,ATF4 and CHOP in rat brain tissue. Results Compared with the blank group,the pyramidal cells in the hippocampal CA1 region of the model group were edema,irregularly arranged,and the cytoplasm was loose and lightly stained. The intensity of red fluorescence in hippocampal CA1 region was significantly increased (P<0.01). The content of MDA in brain tissue was significantly increased(P<0.01),and the activity of GSH was significantly decreased (P<0.01). The protein expression levels of p-PERK/PERK,p-eIF2α/eIF2α,ATF4 and CHOP in brain tissue were significantly increased (P<0.01). The mRNA expression levels of PERK,eIF2α,ATF4 and CHOP in brain tissue were significantly up-regulated(P<0.01). Compared with the model group,the pyramidal cells in the hippocampal CA1 region of the rats in positive drug group and Siwei Huangqi Powder groups were closely arranged,the boundary was clear,and the cell edema was improved. The intensity of red fluorescence in hippocampal CA1 region was significantly decreased (P<0.05). The content of MDA in brain tissue was significantly decreased (P<0.01),and the activity of GSH was significantly increased (P<0.05,P<0.01). The protein expressions of p-PERK/PERK,p-eIF2α/eIF2α,ATF4 and CHOP in the brain tissue of the high-and medium-dose of Siwei Huangqi Powder groups were significantly decreased (P<0.05,P<0.01),while the mRNA expression levels of PERK,eIF2α,ATF4 and CHOP were significantly down-regulated(P<0.05,P<0.01). The protein expressions of p-eIF2α/eIF2α and CHOP in the brain tissue of the low-dose Siwei Huangqi Powder group were significantly decreased (P<0.05,P<0.01),while the mRNA expression levels of eIF2α and CHOP were significantly down-regulated (P<0.05,P<0.01). Conclusions Siwei Huangqi Powder can reduce the edema of neuronal cells in brain tissue,increase the ability of anti-oxidative stress,and reduce the apoptosis of brain neuronal cells in rats with high-altitude hypoxia-induced brain injury,possibly by regulating the PERK/eIF2α/ATF4/CHOP signaling pathway to inhibit endoplasmic reticulum stress.
万方数据
维普
