温胆汤对精神分裂症模型大鼠海马组织PI3K,Akt和GSK3β的影响

Effect of Wendantang on PI3K,Akt and GSK3β of Hippocampus in Rats with Schizophrenia

目的:研究温胆汤对精神分裂症模型鼠海马组织磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)/糖原合成酶激酶3β(GSK3β)信号通路的影响。方法:将60只大鼠随机分为6组,分别为正常组、模型组、氯氮平组、温胆汤高、中、低剂量组,每组10只。正常组和模型组灌胃生理盐水,氯氮平组灌胃氯氮平原药20mg·kg^-1;温胆汤高、中、低剂量组分别灌胃温胆汤生药40,20,10g·kg^-1;1次/d,共21d。在最后1次给药2h后,除正常组外,其余各组采用一次性左侧腹腔注射MK8010.6mg·kg^-1,以诱发精神分裂症。观察并记录大鼠的刻板行为,3d后,处死并取其海马组织待测。依照SamsDodd和Hoffman标准对大鼠的刻板行为评分;蛋白免疫印迹法(Western blot)测定海马组织PI3K,Akt和GSK3β蛋白表达;实时荧光定量聚合酶链式反应(Real-time PCR)检测海马组织PI3K,Akt,GSK3β mRNA表达。结果:与正常组比较,模型组大鼠刻板行为评分显著升高(P<0.01),海马组织PI3K,Akt,GSK3β蛋白和mRNA表达水平显著下降(P<0.01)。与模型组比较,温胆汤给药组能明显降低大鼠刻板行为评分(P<0.05),升高海马组织PI3K,Akt,GSK3β蛋白和mRNA表达水平(P<0.05,P<0.01)。结论:温胆汤通过改善精神分裂症模型鼠刻板行为、升高其海马组织PI3K,Akt,GSK3β的表达,调控PI3K/Akt/GSK3信号通路,从而达到治疗精神分裂症的目的。

Objective: To research the effect of Wendantang on phosphatidylinositol-3-kinases(PI3 K)/protein kinase B(Akt)/glycogen synthase kinase 3β(GSK3β) signaling pathway of hippocampus in rats with schizophrenia. Method: Sixty SD rats were randomly divided six groups: normal group(A),model group(B),Clozapine group(C),high-dosage group Wendantang(D),medium-dosage Wendantang group(E) and low-dosage Wendantang group(F),with 10 rats in each group. The rats of normal group and model group were given normal saline. The rats of Clozapine group were given 20 mg·kg-1 Clozapine. The rats of high-dosage,medium-dosage,low-dosage Wendantang groups were respectively given 40,20,10 g·kg-1 Wendantang,once a day,for 21 days. Two hours later after the last administration with Wendantang or saline,except for group A,groups B,C,D,E,F were intraperitoneally given MK-801 0. 6 mg·kg-1 to establish the rat schizophrenia model. After modeling,the changes in stereotyped behavior of each group were observed and recorded. After three days,the rats were put to death,and the hippocampus tissue were tested. According to Sams Dodd and Hoffman’s standard,the stereotyped behavior of rats was scored. The protein expressions of PI3 K,Akt and GSK3β of hippocampus were determined by Western blot. The mRNA expressions of PI3 K,Akt and GSK3β of hippocampus were tested by Real-time PCR. Result: Compared with A,the stereotyped behavior score of the B was significantly increased(P < 0. 01). The expressions of PI3 K, Akt, GSK3β protein and mRNA of hippocampus were significantly decreased(P < 0. 01) in rats of the B. Compared with the B,Wendantang administration groups could reduce the stereotyped behavior score(P < 0. 05),increased significantly the expressions of PI3 K,Akt,GSK3βprotein and PI3 K,Akt and GSK3β mRNA of hippocampus(P < 0. 05,P < 0. 01). Conclusion: Wendantang could regulate the PI3 K/Akt/GSK3 signaling pathway by improving the stereotyped behavior and increasing the expressions of PI3 K,Akt,GSK3β of hippocampus in rats with schizophrenia,so as to achieve the purpose of treating schizophrenia.