温胆汤对精神分裂症模型鼠海马PKC,p38MAPK及P-Cx43的影响

Effect of Wendan Tang on PKC,p38 MAPK and P-Cx43 of Hippocampus in Rats with Schizophrenia

摘要:

目的: 研究温胆汤对精神分裂症模型鼠大脑蛋白激酶C(PKC),p38丝裂原活化蛋白激酶(p38 MAPK)及磷酸化连接蛋白Cx43(P-Cx43)蛋白表达的影响. 方法: 将72只清洁级 SD 大鼠随机平均分为6组:正常组(A,生理盐水20 mL·kg^-1),模型组(B,生理盐水20 mL·kg^-1),氯氮平组(C,20 mg·kg^-1),温胆汤高剂量组(D,40 g·kg^-1),温胆汤中剂量组(E,20 g·kg^-1),温胆汤低剂量组(F,10 g·kg^-1).A,B组 ig生理盐水;C组 ig氯氮平;D,E,F组分别 ig温胆汤,1次/d,21 d后,B,C,D,E,F组一次性 ip 地卓西平马来酸盐(MK-801) 0.6 mg·kg^-1,建立精神分裂症模型,行为学观察3 d后,处死大鼠,取海马组织,采用蛋白免疫印迹(Western bloting)法检测海马组织中PKC,p38 MAPK及P-Cx43蛋白的含量. 结果: 与正常组相比,模型组大鼠出现刻板行为;海马组织PKC,p38 MAPK及P-Cx43含量明显升高(P< 0.05).与模型组比较,温胆汤各组及氯氮平组均不同程度改善了模型鼠的一般状况;明显降低海马组织PKC,p38 MAPK及P-Cx43的含量(P< 0.05).Cx43的磷酸化程度也有统计学意义(P< 0.05),且模型组磷酸化水平最高. 结论: 温胆汤可明显降低PKC,p38 MAPK及P-Cx43蛋白的浓度,进而调节缝隙连接通讯(GJIC)的功能.

Abstract:

Objective: To study the effects of Wendan Tang on protein kinase C(PKC), p38 mitogen activated protein kinase(p38 MAPK) and phosphorylated connexin43(P-Cx43)of hippocampus in rats with schizophrenia. Method: Seventy-two SD rats were randomly averaging divided six groups:normal group(A,20 mL·kg^-1),model group(B,20 mL·kg^-1),Clozapine group(C,20 mg·kg^-1) and Wendan Tang high-dosage group(D,40 g·kg^-1),Wendan Tang medium-dosage group(E,20 g·kg^-1),Wendan Tang low-dosage group(F,10 g·kg^-1).The A and B groups were given normal saline,the C group was given Clozapine, the D,E,F groups were respectively given Wendan Tang, every day,for 21 days.The B, C, D, E, F groups were ip given dizocipine maleate(MK-801) 0.6 mg·kg^-1 to establish rat schizophrenia model, and stereotyped behavior of rats were observed. After three days, the rats were sacrificed and the hippocampus tissue was tested. The expressions of PKC,p38 MAPK,P-Cx43 in hippocampus tissue was determined by Western bloting. Result: Compared with A group, rats of B group appeared stereotyped behavior,the expressions of PKC, p38 MAPK,P-Cx43 in hippocampus tissue was increased(P <0.05).Compared with B group,stereotyped behavior was improved,Wendan Tang could significantly decrease the expression of PKC,p38 MAPK,P-Cx43 in hippocampus tissue(P <0.05).The degree of phosphorylation of Cx43 is also statistically significant(P <0.05) and the highest level of phosphorylation in the model group. Conclusion: Wendan Tang can significantly reduce concentration of PKC,p38 MAPK and P-Cx43,thereby regulating gap junction intercellular communication(GJIC) function.