基于病证模型研究茯苓抗焦虑作用

A Preliminary Investigation on the Anti Anxiety Effect of Fuling Based on Disease Syndrome Model

目的:观察茯苓对焦虑小鼠、脾阳虚焦虑大鼠、脾阴虚焦虑大鼠的抗焦虑作用,并探讨其作用机制。方法:以小鼠焦虑模型、脾阳虚大鼠焦虑模型、脾阴虚大鼠焦虑模型观察并记录各组小鼠/大鼠的OE%、OT%以及穿梭次数。采用ELISA法测定小鼠脑组织中GABA、GLU、5-HT、DA的含量及脾阳虚焦虑大鼠、脾阴虚焦虑大鼠海马组织中GABA、GLU的含量及GABA-T、GAD、GS的活性;HE染色法观察脾阳虚焦虑大鼠、脾阴虚焦虑大鼠海马组织DG、CA1、CA3区的病理变化;免疫组化法半定量分析海马组织中GABAARα1受体的表达。结果:与正常对照组比较,模型对照组小鼠/大鼠脑内GABA含量明显降低(P<0.05或P<0.01),GLU、5-HT、DA含量明显升高(P<0.05或P<0.01),GAD、GS活性明显降低(P<0.05或P<0.01),GABA-T活性明显升高(P<0.05或P<0.01),海马DG区、CA1区GABAARα1受体的阳性表达明显下调(P<0.05或P<0.01)。与模型对照组比较,茯苓水煎液4 g/kg~15 g/kg能够明显提高焦虑小鼠/大鼠的OE%、OT%以及穿梭次数(P<0.05或P<0.01),能够不同程度改善上述小鼠/大鼠脑内神经递质含量,上调GABAARα1受体的阳性表达(P<0.05或P<0.01)。结论:茯苓具有一定的抗焦虑作用,作用机制为:通过增强GAD、GS活性、抑制GABA-T活性,从而保持GABA与GLU含量的动态平衡;还能够改善海马的病理损伤、增加DG区GABAARα1受体的阳性表达。

Objective:To observe the anti-anxiety effect of Fuling(茯苓)on anxious mice,anxious rats with Piyangxu(脾阳虚)syndrome,and anxious rats with Piyinxu(脾阴虚)syndrome,and explore its underlying mechanism.Methods:The anxiety model in mice,the anxiety model with Piyangxu in rats,and the anxiety model with Piyinxu in rats were induced.The open arm entries(OE%),time in the open arm(OT%),and the number of crossings of mice/rats in each group were recorded.The content of GABA,Glu,5-HT,and DA in the brain tissues of mice,the content of GABA and Glu,and the activities of GABA-T,GAD,and GS in the hippocampus of the anxious rats with Piyangxu and Piyinxu syndromes were measured by ELISA.The pathological changes in the hippocampal DG,CA1,and CA3 areas of the anxious rats with Piyangxu and Piyinxu syndromes were observed by HE staining.The expression of GABAARα1 in the hippocampus was semi-quantitatively analyzed by immunohistochemistry.Results:Compared with the normal control group,the model group showed decreased GABA content in the brain(P<0.05 or P<0.01),increased content of GLU,5-HT,and DA(P<0.05 or P<0.01),blunted GAD and GS activities(P<0.05 or P<0.01),potentiated GABA-T activity(P<0.05 or P<0.01),and down-regulated positive expression of GABAARα1 in the hippocampal DG and CA1 areas(P<0.05 or P<0.01).Fuling Decoction at 4-15 g/kg increased OE%,OT%,and the number of crossings in anxious rats/mice(P<0.05 or P<0.01),reduced the content of the above-mentioned neurotransmitters in the brain,and up-regulated the positive expression of GABAARα(P<0.05 or P<0.01)as compared with the conditions in the model group.Conclusion:The anti-anxiety effect possessed by Fuling is achieved by potentiating the activities of GAD and GS and blunting the activity of GABA-T to maintain the dynamic balance between GABA and Glu.Fuling can also improve the pathological damage in the hippocampus and increase the positive expression of GABAARα1 in the hippocampal DG area.