Shen Yang1, Fangbo Ning1, Juan Li1, Dongmei Guo1, Li Zhang2, Ruiting Cui1, Yunlin Liu3. 1. Department of Neurology, Tai'an City Central Hospital, Tai'an City, Shandong Province, China. 2. Department of Respiratory Intensive Care Unit, Tai'an City Central Hospital, Tai'an City, Shandong Province, China. 3. Department of Neurology, Tai'an City Central Hospital, Tai'an City, Shandong Province, China. Electronic address: atyl_liu@126.com.
Abstract
OBJECTIVE: The objective of this study is to investigate the therapeutic effect of sinomenine (SIN) on rat cerebral ischemia-reperfusion (IR) injury and the molecular mechanism. METHODS: One hundred thirty-five rats were equally randomized into sham-operated group, middle cerebral artery occlusion (MCAO) group, and SIN group, and reversible rat MCAO model was made according to the Longa method for the MCAO and SIN groups. Then, 15 rats from each group were decapitated at 6, 12, and 24 hours after reperfusion to obtain brain tissue samples. Rats in the SIN group were injected with sinomenine by tail vein (90 mg/kg) 1 hour before ischemia; rats in the MCAO and sham-operated groups were administrated with the same volume of saline. Neurological severity score (NSS), infarction volume, ischemic brain water content, and blood-brain barrier (BBB) permeability were determined at corresponding time points. Acid-sensing ion channel (ASIC) 1a mRNA level was determined by quantitative real-time polymerase chain reaction; ischemic brain contents of lactic acid (LD), lactic dehydrogenase (LDH), ATPase, and inflammatory factors were determined by spectrophotometric method. RESULTS: At 12 hours after reperfusion and since then, NSS in the SIN group decreased obviously; infarction volume, brain water content, and BBB permeability in the SIN group were lower than those in the MCAO group (P < .05). IR injury resulted in the upregulation of the contents of ASIC1a mRNA, LD, LDH, and inflammatory factors and the downregulation of the contents of ATPase, while SIN could reverse the upregulation/downregulation effect induced by IR injury (P < .05). CONCLUSION: Through its anti-inflammation effect, which alleviates acidosis, improves energy metabolism, and inhibits ASIC1a level, SIN protects ischemic rat brain against cerebral IR injury.
OBJECTIVE: The objective of this study is to investigate the therapeutic effect of sinomenine (SIN) on rat cerebral ischemia-reperfusion (IR) injury and the molecular mechanism. METHODS: One hundred thirty-five rats were equally randomized into sham-operated group, middle cerebral artery occlusion (MCAO) group, and SIN group, and reversible ratMCAO model was made according to the Longa method for the MCAO and SIN groups. Then, 15 rats from each group were decapitated at 6, 12, and 24 hours after reperfusion to obtain brain tissue samples. Rats in the SIN group were injected with sinomenine by tail vein (90 mg/kg) 1 hour before ischemia; rats in the MCAO and sham-operated groups were administrated with the same volume of saline. Neurological severity score (NSS), infarction volume, ischemic brain water content, and blood-brain barrier (BBB) permeability were determined at corresponding time points. Acid-sensing ion channel (ASIC) 1a mRNA level was determined by quantitative real-time polymerase chain reaction; ischemic brain contents of lactic acid (LD), lactic dehydrogenase (LDH), ATPase, and inflammatory factors were determined by spectrophotometric method. RESULTS: At 12 hours after reperfusion and since then, NSS in the SIN group decreased obviously; infarction volume, brain water content, and BBB permeability in the SIN group were lower than those in the MCAO group (P < .05). IR injury resulted in the upregulation of the contents of ASIC1a mRNA, LD, LDH, and inflammatory factors and the downregulation of the contents of ATPase, while SIN could reverse the upregulation/downregulation effect induced by IR injury (P < .05). CONCLUSION: Through its anti-inflammation effect, which alleviates acidosis, improves energy metabolism, and inhibits ASIC1a level, SIN protects ischemicrat brain against cerebral IR injury.