Effects of κ opioid receptor agonist on cognitive function and expression of p-tau and Aβ in hippocampus of rats undergoing cardiopulmonary bypass
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摘要:目的
探讨κ阿片受体(KORs)激动剂对体外循环(CPB)术后大鼠认知功能及海马组织p-tau、Aβ蛋白表达的影响。
方法选取40只清洁级成年雄性SD大鼠, 采用随机数字表法分为假手术组(S组)、CPB组(C组)、CPB+KORs激动剂U50488H组(U组)、CPB+KORs拮抗剂Nor-BNI+KORs激动剂U50488H组(N组), 每组10只。术前, 各组大鼠均进行为期5 d(4次/d)的水迷宫训练。S组仅穿刺置管, 不进行CPB; C组行动静脉穿刺置管, 且进行CPB 1 h; U组于CPB前30 min静脉注射U50488H 1.5 mg/kg, 其余同C组; N组于CPB前1 h静脉注射Nor-BNI 2.0 mg/kg, 其余同U组。CPB术后第3天水迷宫测试结束后, 将大鼠放血处死后取海马组织, 采用酶联免疫吸附试验(ELISA)法检测Aβ蛋白含量, 采用蛋白质印迹法(Western blot)检测p-tau蛋白表达情况。
结果与S组相比, 其余3组大鼠逃避潜伏期均延长, 穿越平台次数、目标象限游泳距离和停留时间均减少, 海马组织中p-tau蛋白表达、Aβ蛋白含量均增加, 差异有统计学意义(P < 0.05); 与C组相比, U组大鼠逃避潜伏期缩短, 穿越平台次数、目标象限游泳距离和停留时间增加, 海马组织p-tau蛋白表达、Aβ蛋白含量降低, 差异有统计学意义(P < 0.05); N组各项指标与C组相比, 差异无统计学意义(P>0.05)。
结论KORs激动剂可减少海马组织中p-tau、Aβ蛋白表达, 且或许由此发挥对CPB术后大鼠认知功能的保护作用。
Abstract:ObjectiveTo investigate the effect of κ opioid receptors (KORs) on cognitive function and the expression of p-tau and Aβ in hippocampus of rats after cardiopulmonary bypass(CPB).
MethodsA total of 40 clean grade adult male SD rats were randomly divided into four groups: sham operation group (n=10, group S), CPB group (n=10, group C), CPB+KORs agonists U50488H group (n=10, group U), CP B+KORs antagonist Nor-BNI+U50488H group (n=10, group N). Before operation, rats in each group were given water maze training for 5 days, four times a day. In group S, only arteriovenous catheterization was performed without CPB. In group C, arteriovenous catheterization was performed with CPB for 1 hour. In group U, U5-0488H for 1.5 mg/kg was intravenously injected 30 minutes before CPB, and the rest performance was the same to group C. In group N, Nor-BNI for 2 mg/kg was intravenously injected 1 hour before CPB, and the rest performance was the same as in group U. On the 3rd day of operation after the water maze training, rats were killed by bloodletting and hippocampus tissue was taken off. Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of Aβ. Western blot was used to detect the expression of p-tau.
ResultsCompared with the group S, the escape latency of rats in the other three groups was prolonged, the number of crossing platform, swimming distance and stay time in target quadrant were significantly reduced, the expression of p-tau protein and the content of Aβ protein in hippocampus were significantly increased (P < 0.05); compared with the group C, the escape latency of rats in the group U was significantly shortened, the number of crossing platform and swimming distance in target quadrant were significantly increased, the stay time was longer, and the expression of p-tau and the content of Aβ decreased (P < 0.05), while there were no significant differences in above indicators between group N and group C (P>0.05).
ConclusionKORs agonists can reduce the expression of p-tau and Aβ proteins in hippocampal tissue, and may thus play a protective role in cognitive function of rats after CPB.
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Keywords:
- κ opioid receptors /
- cardiopulmonary bypass /
- cognitive impairment /
- brain protection /
- hippocampus /
- water maze
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表 1 各组大鼠术后隐藏平台潜伏期和游泳速度比较(x±s)
指标 S组(n=10) C组(n=10) U组(n=10) N组(n=10) 隐藏平台潜伏期/s 10.44±0.78 33.16±1.75* 18.20±0.97*# 30.93±1.22* 游泳速度/(mm/s) 237.47±10.37 229.34±19.33 233.42±12.65 226.18±16.31 与S组比较, *P < 0.05; 与C组比较, #P < 0.05。 
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表 2 各组大鼠术后穿越平台次数、游泳距离、停留时间比较(x±s)
指标 S组(n=10) C组(n=10) U组(n=10) N组(n=10) 穿越平台次数/次 5.33±0.58 1.33±0.58* 3.33±0.53*# 1.67±1.15* 游泳距离/cm 634.02±39.01 370.22±25.32* 490.01±22.49*# 368.51±34.60* 停留时间/s 41.14±1.62 28.12±2.08* 34.25±1.99*# 27.88±1.74* 与S组比较, *P < 0.05; 与C组比较, #P < 0.05。
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表 3 各组大鼠海马组织中p-tau蛋白表达和Aβ蛋白含量比较(x±s)
指标 S组(n=10) C组(n=10) U组(n=10) N组(n=10) Aβ蛋白/(pg/mL) 6 821.40±160.82 11 301.33±648.77* 8 714.39±16.69*# 10 013.12±82.48* p-tau/tau 0.19±0.21 0.95±0.43* 0.61±0.56*# 0.85±0.51* 与S组比较, *P < 0.05; 与C组比较, #P < 0.05。
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