摘要
【目的】探讨瞬时受体电位香草素受体亚型4(TRPV4)激动剂对大鼠脑缺血再灌注损伤(I/R)的保护作用及相关机制。【方法】72只大鼠随机分为Sham组、I/R组、4-α-佛波醇-12,13-二癸酸(4α-PDD)组、LY294002组,每组18只。建模前30 min,4α-PDD组尾静脉注射4α-PDD 0.2 mg/kg,LY294002组尾静脉注射4α-PDD 0.2 mg/kg和LY2940020.5 mg/kg,Sham组、I/R组尾静脉注射等体积生理盐水,均为一次性给药。I/R后24 h检测大鼠神经功能和脑梗死体积;检测离体脑基底动脉(CBA)舒张功能;免疫印迹法检测脑组织蛋白激酶B(AKT)、p-AKT、内皮型一氧化氮合酶(eNOS)、p-eNOS蛋白表达。【结果】与I/R组比较,4α-PDD组神经功能评分降低,脑梗死体积减小(P<0.05);与4α-PDD组比较,LY294002组神经功能评分升高,脑梗死体积增大(P<0.05)。与Sham组比较,I/R组CBA舒张率增加(P<0.05);与I/R组比较,4α-PDD组CBA舒张率增加(P<0.05);与4α-PDD组比较,LY294002组CBA舒张率降低(P<0.05)。HE染色结果显示,Sham组海马神经元核仁清晰、着色均匀、染色质少,排列整齐、胞体表现为椭圆形或圆形;I/R组神经元大量变形、坏死,胞核浓缩、固染,排列杂乱;4α-PDD组、LY294002组神经元数量较I/R组增加,坏死程度改善,其中4α-PDD组改善程度优于LY294002组。与Sham组比较,I/R组p-AKT/AKT、p-eNOS/eNOS升高(P<0.05);与I/R组比较,4α-PDD组p-AKT/AKT、p-eNOS/eNOS升高(P<0.05);与4α-PDD组比较,LY294002组p-AKT/AKT、p-eNOS/eNOS降低(P<0.05)。【结论】TRPV4激动剂可改善脑I/R大鼠神经功能及海马区病理变化,促进CBA舒张,减小脑梗死体积,其可能通过激活PI3K/AKT/eNOS通路来实现。
【Objective】To investigate the protective effect of transient receptor potential vanilloid subtype 4(TRPV4)on cerebral ischemia-reperfusion(I/R)injury in rats,and to explore related mechanisms.【Methods】A total of 72 rats were randomly divided into the sham group,the I/R group,the 4-α-phorbol-12,13-didecanoic acid(4α-PDD)group,and the LY294002 group,with 18 rats in each group.At 30 minutes point before modeling,the 4α-PDD group was injected with 4α-PDD 0.2 mg/kg through the tail vein,the LY294002 group was injected with 4α-PDD 0.2 mg/kg and LY2940020.5 mg/kg,while the sham group and the I/R group,was injected with an equal volume of normal saline into the tail vein.All pretreatments were one-time medications.The nerve function at 24 h after I/R were detected.The cerebral infarct volume was measured as well.The diastolic function of the isolated cerebral basilar artery(CBA)was evaluated.The expressions of protein kinase B(AKT),p-AKT,endothelial nitric oxide synthase(eNOS)and p-eNOS in brain tissue were detected by western blotting.【Results】Compared to the I/R group,the nerve function score and cerebral infarction volume decreased in the 4α-PDD group(P<0.05).While compared to the 4α-PDD group,the nerve function score and cerebral infarction volume increased in the LY294002 group(P<0.05).Then,compared with the sham group,the CBA diastolic rate in the I/R group increased(P<0.05);While the CBA diastolic rate increased in the 4α-PDD group(P<0.05)if it was compared with that in the I/R group,However,compared with the 4α-PDD group,the CBA diastolic rate decreased in the LY294002 group(P<0.05).The result of HE staining showed that the hippocampal neuronal nucleoli in the sham group were clear,uniform color,less chromatin,neat arrangement in rows,and oval or round shape in cell body;while the I/R group had large deformation and necrosis of neurons,plus condensed,solid dye,and disorderly arranged nucleuses.However,compared to the I/R group,the number of neurons and the degree of neuronal necrosis in both
作者
高海茸
郝艳
GAO Hai-rong;HAO Yan(Department of Neurology,People's Hospital of Yan'an,Yan'an Shaanxi 716000)
出处
《医学临床研究》
CAS
2023年第3期344-347,351,共5页
Journal of Clinical Research
