槐果碱拮抗酸敏感离子通道及其在大鼠缺血性脑损伤中的保护作用

目的 探讨槐果碱对酸敏感离子通道(acid-sensing ion channel,ASIC)的影响及其在缺血性脑损伤大鼠中的神经保护作用.方法 25只SD大鼠随机分为假手术组、脑缺血再灌注组以及槐果碱5、10和20 mg/kg预处理组,每组5只.采用线栓法建立局灶性大鼠缺血模型,5、10和20 mg/kg槐果碱腹腔注...

Neuroprotective effect of sophocarpine against transient focal cerebral ischemia via down-regulation of the acid-sensing ion channel 1 in rats

Objective To investigate the neuroprotective effect of sophocarpine against transient focal cerebral ischemia via down-regulation of the acid-sensing ion channel 1(ASICl) in rats.Methods Twenty-five SD rats were randomly allocated into sham operation,cerebral ischemia/reperfusion,and 5,10,and 20 mg/kg sophocarpine pretreatment groups (n=5 in each group).A rat focal ischemia model was induced by the intraluminal suture method.Five,10 and 20 mg/kg sophocarpine were injected intraperitoneally for pretreatrnent.2,3,5-triphenyltetrazolium chloride staining was used to detect cerebral infarct volume.TUNEL staining was used to detect apoptosis.Immunohistochemistry and Western blot were used to detect the expression of ASIC1 and ASIC2.Results The infarct volume after ischemia-reperfusion was(181.21±9.21)mm3,while the 5,10,and 20 mg/kg sophocarpine pretreatment groups were(150.12±6.19),(52.31±4.20),and(32.18±3.82)mm3,respectively;the neurological function scores in the cerebral ischemia/reperfusion group was(3.62±0.36),while the 5,10,and 20 mg/kg sophocarpine pretreatment grows were(3.15±0.36),(1.92±0.18),and(1.85±0.21),respectively;The surviving neurons only accounted for(31.2±2.8)% of the total cell number in the cerebral ischemia-reperfusion group,while they accounted for(51.2±3.7)%,(76.5±2.1)%,and(77.1±4.1)% in the 5,10,and 20 mg/kg sophocarpine pretreatnmat groups.Compared with the cerebral ischemia/reperfusion group,the cerebral infarct volume was decreased significantly in the sophocarpine pretreatrnent groups(all P<0.01),the neurological function scores were decreased significantly(all P<0.01),and the number of apoptotic cells was decreased significantly (all P<0.01).Immunohistochemistry showed that the number of ASIC-1 positive cells in the sham operation,cerebral ischemia-reperfusion,and 5,10,and 20 mg/kg sophocarpine pretreatment groups were(162.5±8.3),(165.1±5.3),(138.3±7.2),(82.1±6.3),and(69.2±5.5)/mm respectively;Western blot showed that the ASIC1 protein expression was decreased sigaificantly in the 10 and 20 mg/ky sophocarpine pretreatment groups (P<0.01),while there WaS no significant difference in the ASIC2 protein expression.Condusions Sophocarpine may play a neuroprotective role for cerebral ischemia-reperfusion injury in rats via down-regulating the expression of ASIC1 protein.