红景天苷对术后认知功能及海马核因子-kB、低氧诱导因子-1a和凋亡相关蛋白表达的影响

Effects of salidroside on the cognitive function and expression of nuclear factor-kB,hypoxia-inducible factor-1a,apoptosis-related proteins after operation

目的观察红景天苷(salidroside,SAL)对肝部分切除术后老年小鼠认知功能及海马NF-κB、低氧诱导因子(hypoxia-inducible factor,HIF)-1α和凋亡相关蛋白表达的影响,探讨NF-κB、HIF-1α和凋亡相关蛋白[B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)、Bcl-2相关X蛋白(Bcl-2 related X protein,Bax)、含半胱氨酸的天冬氨酸蛋白水解酶3(caspase-3)]在术后认知功能障碍(post-operative cognitive dysfunction,POCD)发病机制中的作用。方法健康雄性C57B/6小鼠48只,18月龄,体重25~35 g,采用随机数字表法将其分为3组(每组16只):假手术组(sham组)、手术生理盐水组(手术组)和SAL组,根据手术后测试时点不同分为术后1、3 d两个亚组,每亚组8只。手术组和SAL组行肝部分切除术建立手术模型,SAL组小鼠腹腔注射SAL;sham组在肝部分切除术相同手术部位做切开缝合术。用Morris水迷宫测试小鼠的学习记忆能力,采用Western blot法检测海马NF-κB、HIF-1α、Bcl-2、Bax及caspase-3表达。结果与sham组比较,手术组术后1、3 d逃避潜伏期明显延长,空间探索跨越平台次数减少,海马NF-κB、HIF-1α、Bax、caspase-3表达增加,Bcl-2表达减少(P<0.01);与手术组比较,SAL组逃避潜伏期缩短,空间探索跨越平台次数增加,海马NF-κB、HIF-1α、Bax、caspase-3表达减少,Bcl-2表达增加(P<0.05)。结论POCD的发病机制与海马NF-κB、HIF-1α及凋亡相关蛋白表达有关,SAL通过抑制NF-κB、HIF-1α及凋亡相关蛋白表达改善肝部分切除术后小鼠的认知功能。

Objective To investigate the effects of salidroside(SAL)on the cognitive function and expression of nuclear factor-κB(NF-κB),hypoxia-inducible factor-1α(HIF-1α)and apoptosis-related proteins in the hippocampus of aged mice after partial hepatectomy,and to discusse the role of NF-κB,HIF-1αand apoptosis-related proteins[B-cell lymphoma-2(Bcl-2),Bcl-2 related X protein(Bax)and caspase-3]in the pathogenesis of post-operative cognitive dysfunction(POCD).Methods Forty eight healthy male C57B/6 mice,aged 18 months,weight 25-35 g,were used in the study.These mice were randomly divided into three groups(n=16),using a random number table:a sham operation group(a sham group),an operation+normal saline group(an operation group)and a SAL group.Each group was subdivided into two groups(n=8)according to the test time points after operation:a 1 d after operation group and a 3 d after operation group.An operation model was established by partial hepatectomy in the operation and SAL groups.Mice in the SAL group were intraperitoneally injected with SAL.Mice in the sham group were incised and sutured at the same surgical site with partial hepatectomy.The Morris water maze was used to determine learning and memory ability.The hippocampi of these mice were isolated for detection of the expression of NF-κB,HIF-1α,Bcl-2,Bax and caspase-3 by Western blot.Results Compared with those in the sham group,the escape latency for mice in the operation group 1 and 3 days after operation obviously prolonged and the times to cross the platform decreased.Furthermore,the expression of hippocampal NF-κB,HIF-1α,Bax and caspase-3 significantly increased,with a decreased level of Bcl-2(P<0.01).Compared with those in the operation group,the escape latency of the SAL group obviously decreased and the times to cross the platform increased.The expression of hippocampal NF-κB,HIF-1α,Bax and caspase-3 significantly decreased,with an increased level of Bcl-2(P<0.05).Conclusions The pathogensis of POCD is associated with the expression of hippocampal NF-κB,HIF-1αand apoptosis-related proteins.SAL can improve the cognitive function of mice after partial hepatectomy through inhibiting the expression of NF-κB,HIF-1αand apoptosis-related proteins.