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目的研究急性染铅对大鼠海马钙-钙调蛋白-钙调蛋白依赖的蛋白激酶Ⅱ(Ca2+/CaM-CaMKⅡ)信号转导通路下游因子cAMP反应元件结合蛋白(CREB)、c-FOS蛋白表达的影响。方法取生后30d大鼠海马,将其切成350μm脑片,置于人工脑脊液(ACSF)液内稳定培养2h后,将其分为4组,对照组(ACSF液)、激活剂组(含谷氨酸的ACSF液)、抑制剂组(含KN-93的ACSF液)、染铅组(含谷氨酸及醋酸铅的ACSF液)。30min后收集脑片,采用免疫印迹法检测谷氨酸、KN-93及染铅对CREB、c-FOS的表达的影响。结果大鼠海马脑片培养时,各组总量的CREB、c-FOS表达差异无统计学意义(P>0.05);与对照组相比,激活剂组活化的CREB、c-FOS表达显著增强,而抑制剂组及染铅组活化的CREB、c-FOS的表达显著降低。结论急性铅中毒对Ca2+/CaM-CaMKⅡ信号转导通路的影响可能通过抑制CaMKⅡ下游因子CREB、c-FOS的活性从而导致学习记忆功能的受损。
Objective To investigate the effect of acute lead exposure on the expression of cAMP response element binding protein (CREB) and c-FOS protein in hippocampal calcium-calmodulin-calmodulin-dependent protein kinase Ⅱ (Ca2 + / CaM-CaMKⅡ) signal transduction pathway Impact. Methods The hippocampus of hippocampus of rats were sacrificed 30 days after the operation. The rats were cut into 350μm slices and then cultured in ACSF for 2 hours. The rats were divided into 4 groups: control group (ACSF), activator group Glutamate ACSF solution), inhibitor group (ACSF solution containing KN-93), and lead exposure group (ACSF solution containing glutamic acid and lead acetate). The brain slices were harvested 30min later and the effects of glutamate, KN-93 and lead exposure on CREB and c-FOS expression were detected by Western blotting. Results There was no significant difference in CREB and c-FOS expression in the hippocampal slices of rats (P> 0.05). Compared with the control group, the expressions of CREB and c-FOS in the activator group were significantly increased , While the expression of CREB and c-FOS in inhibitor group and lead-exposed group was significantly decreased. Conclusion The acute lead poisoning may affect the Ca2 + / CaM-CaMKⅡ signal transduction pathway by inhibiting the activity of CaMKⅡ downstream factors CREB and c-FOS, leading to impaired learning and memory function.