坎地沙坦干預海仁藻酸致癇大鼠腎臟細胞外信號調節激酶的表達及其機制_《華西醫學》

作者：

馬寶新 ¹ ,  吳綏生 ²

1 濱州醫學院附屬醫院心內科（山東濱州，256603）;2吉林大學第一醫院;

關鍵詞：

坎地沙坦癲癇腎臟細胞外信號調節激酶

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【摘要】　目的　探討坎地沙坦干預后海仁藻酸（kainic acid，KA）致癇大鼠腎臟細胞外信號調節激酶（ERK1/2）的表達及其變化的機制。　方法　 105只雄性Wistar大鼠隨機分為3組:A1-5對照組、B1-5 致癇組、C1-5坎地沙坦組，每組各35只，1-5分別表示癲癇后0、2、6、12及24 h。采用立體定位儀下杏仁核內注射KA方法制備大鼠癲癇模型，于致癇后不同時程，進行灌流固定、腎臟組織的石蠟包埋、切片及免疫，組織化學染色，檢測不同時程腎臟ERK1/2表達的灰度值。　結果　與對照組相比，致癇組及坎地沙坦組腎組織于致癇后2 h ERK1/2表達均開始增加（致癇后2 h ERK1/2，致癲組：20 229.18±2 067.27，坎地沙坦組：16 878.19±2 693.97，對照組:8 054.24±975.90， P lt;0.01），致癇后6 h兩組大鼠腎組織ERK1/2的表達均達到高峰（致癇后6 h ERK1/2，致癇組:39 217.34±4 443.33，坎地沙坦組：31 924.85±4 383.80，對照組：8 575.24±1 040.82， P lt;0.01），隨后逐漸下降，致癇后24 h兩組大鼠腎組織ERK1/2表達均回到0 h水平（P gt;0.05），對致癇組及坎地沙坦干預兩組大鼠腎組織ERK1/2蛋白表達進行組間比較結果顯示，坎地沙坦組2 h（致癇組：20 229.18±2 067.27，坎地沙坦組：16 878.19±2 693.97，P lt;0.01）、6 h（致癇組：39 217.34±4 443.33，坎地沙坦組：31 924.85±4 383.80，P lt;0.01）、12 h（致癇組：16 610.11±2 953.03，坎地沙坦組：13 393.16±2 269.42， P lt;0.05）ERK1/2表達降低。　結論　 ERK1/2在KA致癇大鼠腎組織中表現為短時程表達增加，坎地沙坦可使腎組織ERK1/2表達降低。
【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.

引用本文： 馬寶新,吳綏生. 坎地沙坦干預海仁藻酸致癇大鼠腎臟細胞外信號調節激酶的表達及其機制. 華西醫學, 2011, 26(7): 1014-1017. doi: 復制

1.	孫小妹, 毛萌, 周暉, 等. 腦源性神經營養因子對缺氧胚腦皮質神經元發揮保護作用的細胞內信號傳導機制[J]. 華西醫學, 2006, 21(3): 454-456.
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4.	楊小芳, 喻明, 聶本剛, 等. 單次癲癇發作后患者血清和腦脊液中神經元特異性烯醇化酶及髓鞘堿性蛋白的變化[J]. 華西醫學, 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.	馬寶新, 吳綏生, 齊玲, 等. 氯沙坦對老年高血壓患者血液流變學和腎結構的影響[J]. 中華高血壓雜志, 2007, 15(1): 70-71.
12.	趙秀鶴, 遲兆富, 王勝軍, 等. ERK信號轉導通路在癲癇大鼠腦部作用的研究[J]. 神經損傷與功能重建, 2006, 1(1): 14-16.

1. 　孫小妹, 毛萌, 周暉, 等. 腦源性神經營養因子對缺氧胚腦皮質神經元發揮保護作用的細胞內信號傳導機制[J]. 華西醫學, 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. 　楊小芳, 喻明, 聶本剛, 等. 單次癲癇發作后患者血清和腦脊液中神經元特異性烯醇化酶及髓鞘堿性蛋白的變化[J]. 華西醫學, 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. 　馬寶新, 吳綏生, 齊玲, 等. 氯沙坦對老年高血壓患者血液流變學和腎結構的影響[J]. 中華高血壓雜志, 2007, 15(1): 70-71.
12. 　趙秀鶴, 遲兆富, 王勝軍, 等. ERK信號轉導通路在癲癇大鼠腦部作用的研究[J]. 神經損傷與功能重建, 2006, 1(1): 14-16.

《華西醫學》

坎地沙坦干預海仁藻酸致癇大鼠腎臟細胞外信號調節激酶的表達及其機制

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《華西醫學》

坎地沙坦干預海仁藻酸致癇大鼠腎臟細胞外信號調節激酶的表達及其機制

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