氯化锂对沙土鼠前脑缺血后神经细胞凋亡及磷酸化Akt蛋白表达的影响

The effect of lithium chloride on neuronal apoptosis and expression o f Phospho-Akt protein after forebrain ischemia in gerbils

目的:观察沙土鼠前脑缺血后神经细胞凋亡的变化及磷酸化Akt蛋白的表达并探讨氯化锂对其干预作用。方法:夹闭沙土鼠双侧颈总动脉5min,制备前脑缺血损伤模型。沙土鼠72只,随机分为假手术组(SH组)、缺血再灌注组(IR组)、氯化锂预处理组(LI鄄Pre组)、氯化锂治疗组(LI鄄Post组)。依术后处死动物时间的不同,各组再分别分为3个亚组,每个亚组6只动物。采用TUNEL染色法观察海马CA1区神经细胞凋亡的变化,免疫组化(SP法)检测大脑皮质区磷酸化Akt蛋白的表达。结果:①TUNEL染色:脑缺血再灌注后3天,与相应IR组相比较,LI鄄Pre组和LI鄄Post组海马CA1区TUNEL阳性细胞明显减少(P<0.01);②磷酸化Akt免疫组织化学染色:与相应IR组相比较,LI鄄Pre组或LI鄄Post组各时点亚组大脑皮层部位磷酸化鄄Akt阳性细胞表达显著增多(P<0.05或P<0.01)。结论:①氯化锂能显著减轻沙土鼠短暂前脑缺血后海马CA1区神经细胞凋亡;②氯化锂的脑保护作用与其激活PI3鄄K/Akt信号传导通路有关。

Objective: To observe the effect of lithium chloride on neuronal apo ptosis and the expression of Phospho-Akt protein after transient forebrain ische mia in gerbils. Methods: The forebrain ischemia model in gerbil was prepared byc lamping the bilateral common carotid arteries for 5 min. Seventy-two gerbils wer e randomly divided into sham operation group (SH group), ischemia reperfusion gr oup (IR group),group preconditioning with lithium chloride (LI-pre group), and group treating with lithium chloride (LI-Post group). Each group was further di vided into three subgroups respectively, with six gerbils in each subgroup. The change of neuronal apoptosis in the CA1 region was examined by TUNEL staining. T he expression of Phospho-Akt protein in the cortex was examined by immunohistoch emistry staining (SP method). Results: ① Compared with IR group, TUNEL positive cells in LI-Pre or LI-Post group were significantly reduced on the 3rd day afte r reperfusion(P < 0.01); ② The expression of Phospho-Akt protein in the cortex of LI-Pre group or LI-Post group was significantly higher than that of IR group on the 1st, 3rd, 7th day after reperfusion (P < 0.05 or P < 0.01). Conclusion: L ithium chloride can significantly suppress neuronal apoptosis after forebrain is chemia in gerbils. The neuroprotective effect of lithium chloride might be corre lated with the activitation of PI 3-K/Akt signal pathway.