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

Authors：

MA Baoxin ¹ ,  WU Suisheng ²

1. Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256603, P. R. China; 2. the First Hospital of Jilin University, Changchun, Jilin 130021, P. R. China;

Corresponding author：

WU Suisheng, Email: yiyuanmabaoxin@yahoo.com.cn

Keywords：

坎地沙坦; 癫痫; 肾脏; 细胞外信号调节激酶

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【摘要】　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24 h。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2 h ERK1/2表达均开始增加（致痫后2 h ERK1/2，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 lt;0.01），致痫后6 h两组大鼠肾组织ERK1/2的表达均达到高峰（致痫后6 h ERK1/2，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 lt;0.01），随后逐渐下降，致痫后24 h两组大鼠肾组织ERK1/2表达均回到0 h水平（P gt;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2 h（致痫组：20 229.18±2 067.27，坎地沙坦组：16 878.19±2 693.97，P lt;0.01）、6 h（致痫组：39 217.34±4 443.33，坎地沙坦组：31 924.85±4 383.80，P lt;0.01）、12 h（致痫组：16 610.11±2 953.03，坎地沙坦组：13 393.16±2 269.42， P lt;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。
【Abstract】　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, P＜0.01), 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, P＜0.01), 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, P＜0.01; 6 hours, group B: 39 217.34±4 443.33 vs. group C: 31 924.85±4 383.80, P＜0.01; 12 hours, group B: 16 610.11±2 953.03 vs. group C: 13 393.16±2 269.42, P＜0.05).　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.

Citation： MA Baoxin,WU Suisheng. Effect of Candesartan on Extracellular Signal-regulated Kinase Protein Expression of Renal Cells in Epilepsy Rats Induced by Kainic Acid and Its Mechanism. West China Medical Journal, 2011, 26(7): 1014-1017. doi: Copy

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11.	马宝新, 吴绥生, 齐玲, 等. 氯沙坦对老年高血压患者血液流变学和肾结构的影响[J]. 中华高血压杂志, 2007, 15(1): 70-71.
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1. 　孙小妹, 毛萌, 周晖, 等. 脑源性神经营养因子对缺氧胚脑皮质神经元发挥保护作用的细胞内信号传导机制[J]. 华西医学, 2006, 21(3): 454-456.
2. 　Li Y, Peng Z, Xiao B, et al. Activation of ERK by spontaneous seizures in neural progenitors of the dentate gyrus in a mouse model of epilepsy[J]. Exp Neurol, 2010, 224(1): 133-145.
3. 　Houser CR, Huang CS, Peng Z. Dynamic seizure-related changes in extracellular signal-regulated kinase activation in a mouse model of temporal lobe epilepsy[J]. Neuroscience, 2008, 156(1): 222-237.
4. 　杨小芳, 喻明, 聂本刚, 等. 单次癫痫发作后患者血清和脑脊液中神经元特异性烯醇化酶及髓鞘碱性蛋白的变化[J]. 华西医学, 2010, 25(11): 2007-2008.
5. 　Tigaran S, Molgaard H, McClelland R, et al. Evidence of cardiac ischemia during seizures in drug refractory epilepsy patients[J]. Neurology, 2003, 60(3): 492-495.
6. 　Sakuragi S, Tokunaga N, Okawa K, et al. A case of takotsubo cardiomyopathy associated with epileptic seizure: reversible left ventricular wall motion abnormality and ST-segment elevation[J]. Heart Vessels, 2007, 22(1): 59-63.
7. 　Yatabe J, Sanada H, Yatabe MS, et al. Angiotensin II type 1 receptor blocker attenuates the activation of ERK and NADPH oxidase by mechanical strain in mesangial cells in the absence of angiotensin Ⅱ[J]. Am J Physiol Renal Physiol, 2009, 296(5): F1052-1060.
8. 　Feliers D, Kasinath BS. Mechanism of VEGF expression by high glucose in proximal tubule epithelial cells[J]. Mol Cell Endocrinol, 2010, 314(1): 136-142.
9. 　Zhou L, Xue H, Yuan P, et al. Angiotensin AT1 receptor activation mediates high glucose-induced epithelial-mesenchymal transition in renal proximal tubular cells[J]. Clin Exp Pharmacol Physiol, 2010, 37(9): e152-157.
10. 　Sekine S, Nitta K, Uchida K, et al. Possible involvement of mitogen-activated protein kinase in the angiotensin Ⅱ-induced fibronectin synthesis in renal interstitial fibroblasts[J]. Arch Biochem Biophys, 2003, 415(1): 63-68.
11. 　马宝新, 吴绥生, 齐玲, 等. 氯沙坦对老年高血压患者血液流变学和肾结构的影响[J]. 中华高血压杂志, 2007, 15(1): 70-71.
12. 　赵秀鹤, 迟兆富, 王胜军, 等. ERK信号转导通路在癫痫大鼠脑部作用的研究[J]. 神经损伤与功能重建, 2006, 1(1): 14-16.

West China Medical Journal

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

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