益生菌对体外循环老年大鼠围手术期认知功能的影响

Effects of probiotics on the perioperative neurocognitive disorders of elderly rats with cardiopulmonary bypass

目的评价益生菌对CPB老年大鼠围手术期认知功能障碍(perioperative neurocognitive disorders,PND)的影响。方法清洁级老年雄性SD大鼠48只,体重400~450 g,按随机数字表法分为4组(每组12只):假手术组(S组)、益生菌+假手术组(P组)、CPB组(C组)和益生菌+CPB组(H组)。各组又分为术后7 d和术后28 d两个亚组,每组6只。各组大鼠于术后7 d和术后28 d行水迷宫测试后,麻醉下处死大鼠,取右侧海马组织。H-E染色光镜下观察海马组织病理学变化,Western blot检测脑组织中PND相关蛋白β-淀粉样蛋白(amyloidβ-protein,Aβ)及Tau蛋白的变化。结果与S组比较(同时点亚组比较,下同):P组术后7 d和术后28 d的平均潜伏期明显缩短,总路程延长,穿越平台次数增加,停留时间也延长(P<0.05);C组、H组在术后7 d和术后28 d的平均潜伏期均明显延长,总路程缩短,穿越平台次数减少,停留时间也缩短(P<0.05)。与P组比较,C组和H组术后7 d和术后28 d的平均潜伏期明显延长,总路程缩短,穿越平台次数减少,停留时间也缩短(P<0.05)。与C组比较,H组术后7 d和术后28 d的平均潜伏期明显缩短,总路程延长,穿越平台次数增加,停留时间也延长(P<0.05)。H-E染色显示S组和P组大鼠术后7 d和28 d海马CA1区未见明显神经元受损,C组大鼠术后7 d和28 d海马CA1区神经元变性明显,H组大鼠术后7 d和28 d海马CA1区受损较C组减轻。与S组比较,P组大鼠术后7 d和术后28 d海马Aβ和Tau蛋白表达均明显降低(P<0.05),C组、H组大鼠术后7 d和术后28 d海马Aβ和Tau蛋白表达均明显升高(P<0.05)。与C组比较,H组大鼠术后7 d和术后28 d海马Aβ和Tau蛋白表达明显降低(P<0.05)。结论益生菌可降低Aβ及Tau蛋白的表达,从而改善CPB老年大鼠PND。

Objective To observe the effects of probiotics on the perioperative neurocognitive disorders(PND)of elderly rats with cardiopulmonary bypass(CPB).Methods A total of 48 adult male SD rats(SPF grade),weighing 400-450 g were used.According to the random number table method,they were divided into four groups(n=12):a sham operation(group S),a probiotics+sham operation(group P),a CPB surgery(group C),and a probiotics+CPB(group H).Furthermore,each group was divided into two subgroups(n=6):a 7-day group and a 28-day group.The water maze test was performed for each group 7 days and 28 days after surgery.The rats were sacrificed under anesthesia and the right hippocampus was collected.The histological changes of hippocampal tissues were observed by hematoxylin-eosin(H-E)staining.The changes of PND-associated proteins amyloidβ(Aβ)protein and Tau protein in brain tissues were detected by Western blot.Results Compared with group S(compared with the subgroup at the same time,the same below),group P presented remarkably shortened average latency,extended total distance,and increases in the number of platform crossing and the amount of time spent in each quadrant 7 days and 28 days after surgery(P<0.05);groups C and H presented remarkably extended average latency,reduced total distance,and decreases in the number of platform crossing and the amount of time spent in each quadrant 7 days and 28 days after surgery(P<0.05).Compared with group P,groups C and H showed extended average latency,reduced total distance,and decreases in the number of platform crossing and the amount of time spent in each quadrant 7 days and 28 days after surgery(P<0.05).Compared with group C,group H showed shortened average latency,extended total distance,and increases in the number of platform crossing and the amount of time spent in each quadrant 7 days and 28 days after surgery(P<0.05).According to H-E staining,there was no obvious neuronal damage in the hippocampal CA1 region of rats in group S and group P 7 days and 28 days after surgery;the degenerative changes of neurons were obvious in the hippocampal CA1 region of rats in group C 7 days and 28 days after surgery;and the damage in the hippocampal CA1 region of rats in group H was relieved compared with that in group C 7 days and 28 days after surgery.Moreover,compared with the group S,the expression of Aβand Tau proteins significantly decreased in group P 7 days and 28 days after surgery(P<0.05),while the expression of Aβand Tau proteins significantly increased in group H and group C 7 days and 28 days after surgery(P<0.05).Compared with group C,the expression of Aβand Tau proteins significantly decreased in group H 7 days and 28 days after surgery(P<0.05).Conclusions Probiotics can decrease the expression of Aβand Tau proteins,so as to improve the PND of elderly rats with CPB.