急性染铅对大鼠海马Ca^(2+)-CaMKⅡ信号通路影响

Effect of acute lead exposure on Ca^(2+)-CamkⅡ signal in hippocampus in rats

目的探讨急性染铅对大鼠海马Ca2+-Ca2+/钙调蛋白依赖蛋白激酶Ⅱ(CaMKⅡ)信号转导通路影响及作用机制。方法取30 d健康大鼠海马脑片分别用含醋酸铅(20μmol/L)及不含醋酸铅的人工脑脊液(ACSF)孵育,分对照组、谷氨酸组、CaMKⅡ抑制剂(KN-93)组、谷氨酸+醋酸铅组,培养30 min后收集脑片,用Western Blot方法检测谷氨酸组、KN-93组、铅组中环腺苷酸(cAMP)反应元件结合蛋白(CREB)的活性。结果染铅组于染铅0、120min时CREB活性分别为(0.305 6±0.020 8)和(0.172 2±0.023 3),随染铅时间延长明显降低;谷氨酸使磷酸化CREB活性提高47%,对非磷酸化CREB活性无影响;KN-93及谷氨酸+醋酸铅组CREB活性分别下降20%,45%,总量CREB表达无明显改变。结论急性铅中毒可能通过抑制CaMKⅡ活性影响下游信号分子,造成对学习记忆功能的损伤。

Objective To study the effect of acute lead exposure on Ca2＋-CamkⅡ signal in rat hippocampus.Methods Hippocampal slices of 30 days old heathy rat were collected and incubated with lead acetate（20μmol / L） and non-lead acetate in artificial cerebrospinal fluid（ACSF） for the control,glutamate,CaMK Ⅱ inhibitor（KN-93）,and glutamic acid ＋ lead acetate group.Brain slices were collected after 30 min of culture.Western Blot was adopted to detect the activity of cyclic adenosine-3′-5′ monophosphate response element binding protein（CREB）.Results CREB activity in the lead group decreased significantly with the time of lead exposure.CREB activity increased by 47% in glutamate group and decreased by 20%,45% in KN-93 and glutamic acid＋lead acetate groups.There was no significant change in total CREB expression.Conclusion Acute lead poisoning may inhibit the activity of CaMK Ⅱ and affect the downstream signaling molecules resulting in learning and memory damage.