脾切除术对大鼠海马tau表达的影响

Effect of splenectomy on tau expression in rat hippocampus

目的 评价脾切除术对大鼠海马tau表达的影响.方法 SD大鼠105只,随机分为3组,正常对照组（A组,n=15）不给予任何处理,麻醉组（B组,n=45）仅吸入1.5%异氟醚2 h,手术＋麻醉组（C组,n=45）吸入1.5%异氟醚（吸入2 h）麻醉下实施脾切除术.B组和C组分别于麻醉后或术后1、3、7 d时处死15只大鼠,取海马组织,测定海马IL-1β mRNA、TNF-α mRNA、IL-1β、TNF-α、总tau、苏氨酸第205位点磷酸化tau（pT205 tau）、丝氨酸第396位点磷酸化tau（pS396 tau）、总糖原合成酶-3β（GSK-3β）和磷酸化GSK-3β（p-GSK-3β）的表达水平.结果 与A组比较,B组各时点IL-1β mRNA、TNF-α mRNA、IL-1β、TNF-α、总tau、pT205 tau、pS396 tau、GSK-3β和p-GSK-3β的表达水平差异无统计学意义（P＞0.05）,C组术后IL-1βmRNA、TNF-α mRNA、IL-1β、pT205 tau和pS396 tau的表达上调,p-GSK-3β表达下调（P＜0.05或0.01）.结论 手术创伤可导致大鼠海马tau磷酸化,其机制与手术创伤诱发炎性反应,从而激活GSK-3β有关.

Objective To investigate the effect of splenectomy on tau expression in rat hippocampus.Methods One hundred and five male SD rats aged 6 months weighing 350-400 g were randomly divided into 3 groups： group A control （n = 15）; group B anesthesia （n =45） and group C surgery （n =45）. The animals were anesthetized, intubated and mechanically ventilated. In group B and C the animals were anesthetized with 1.5% isoflurane for 2 h. In group C splenectomy was performed. The animals were killed on the 1st, 3rd and 7th day after anesthesia and surgery. The hippocampi were immediately removed for determination of IL-1 and TNF-α mRNA and protein expression, expression of total tau, phosphorylated tau at Thr-205 and Ser-396 and activity of glycogen synthase kinase-3 beta （GSK-3β）. Results There was no significant difference in the expression of phosphorylated tau at Thr-205 and Ser-396 between control and anesthesia groups. Surgery significantly increased the expression of IL-1β and TNF-α and induced rapid and massive hyperphosphorylation of tau at Thr-205 and Ser-396 epitope in the hippocampus and activation of GSK-3β. Conclusion Surgical trauma induces inflammatory response in hippocampus, activates GSK-3β and increases phosphorylation of tau.