坎地沙坦干预海仁藻酸致痫大鼠肾脏细胞外信号调节激酶的表达及其机制

Effect of Candesartan on Extracellular Signal-regulated Kinase Protein Expression of Renal Cells in Epilepsy Rats Induced by Kainic Acid and Its Mechanism

目的探讨坎地沙坦干预后海仁藻酸(kainic acid,KA)致痫大鼠肾脏细胞外信号调节激酶(ERK1/2)的表达及其变化的机制。方法 105只雄性Wistar大鼠随机分为3组:A1-5对照组、B1-5致痫组、C1-5坎地沙坦组,每组各35只,1-5分别表示癫痫后0、2、6、12及24h。采用立体定位仪下杏仁核内注射KA方法制备大鼠癫痫模型,于致痫后不同时程,进行灌流固定、肾脏组织的石蜡包埋、切片及免疫,组织化学染色,检测不同时程肾脏ERK1/2表达的灰度值。结果与对照组相比,致痫组及坎地沙坦组肾组织于致痫后2hERK1/2表达均开始增加(致痫后2hERK1/2,致癫组:20 229.18±2 067.27,坎地沙坦组:16 878.19±2 693.97,对照组:8 054.24±975.90,P<0.01),致痫后6h两组大鼠肾组织ERK1/2的表达均达到高峰(致痫后6hERK1/2,致痫组:39 217.34±4 443.33,坎地沙坦组:31 924.85±4 383.80,对照组:8 575.24±1 040.82,P<0.01),随后逐渐下降,致痫后24h两组大鼠肾组织ERK1/2表达均回到0h水平(P>0.05),对致痫组及坎地沙坦干预两组大鼠肾组织ERK1/2蛋白表达进行组间比较结果显示,坎地沙坦组2h(致痫组:20 229.18±2 067.27,坎地沙坦组:16 878.19±2 693.97,P<0.01)、6h(致痫组:39 217.34±4 443.33,坎地沙坦组:31 924.85±4 383.80,P<0.01)、12h(致痫组:16 610.11±2 953.03,坎地沙坦组:13 393.16±2 269.42,P<0.05)ERK1/2表达降低。结论 ERK1/2在KA致痫大鼠肾组织中表现为短时程表达增加,坎地沙坦可使肾组织ERK1/2表达降低。

Objective To study the effect of candesartan on extracellular signal-regulated kinase（ERK） 1/2 protein expression of renal cells in epilepsy rats induced by kainic acid（KA） and its mechanism.Methods A total of 105 male Wistar rats were randomly divided into three groups：control group（A1-5,n=35）,epilepsy group（B1-5,n=35）,and candesartan group（C1-5,n=35）.The sign 1-5 meant respectively 0,2,6,12,and 24 hours after epilepsy.Epilepsy rat models were made by injecting KA into amygdala under three-dimensional positioning devices.Lavage fixation,paraffin embedding of the renal tissue,and immunohistological test were carried out at different time points after epilepsy was induced,and ERK1/2 protein expression level was tested.Results Compared with the control group,the protein expression of ERK1/2 increased significantly 2 hours after epilepsy in groups B and C（ERK1/2 level 2 hours after epilepsy,group B：20 229.18±2 067.27,group C：16 878.19±2 693.97 vs.group A：8 054.24±975.90,P0.01）,and both attained its peak 6 hours after epilepsy（ERK1/2 level 6 hours after epilepsy,group B：39 217.34±4 443.33,group C：31 924.85±4 383.80 vs.group A：8 575.24±1 040.82,P0.01）,and then decreased gradually to the level immediately after epilepsy 24 hours later.There were significant differences in the level of ERK1/2 protein expression between group B and C 2,6,and 12 hours after epilepsy was induced（2 hours,group B：20 229.18±2 067.27 vs.group C：16 878.19±2 693.97,P0.01;6 hours,group B：39 217.34± 4 443.33 vs.group C：31 924.85±4 383.80,P0.01;12 hours,group B：16 610.11±2 953.03 vs.group C：13 393.16±2 269.42,P0.05）.Conclusions The Extracellular signal-regulated kinase1/2 protein expression of renal tissue in epilepsy rats induced by KA increases shortly after epilepsy.Candesartan can decrease the protein expression of ERK1/2 in the renal tissue of epilepsy rats.