帕病1号方对帕金森病模型大鼠的神经保护作用

Neuroprotection of Pabing Formula I for Rats with Parkinson's Disease

目的探讨帕病1号方颗粒对帕金森病(PD)模型大鼠发挥神经保护作用的机制。方法采用6-羟基多巴胺纹状体两点注射法造成左侧纹状体损毁模型大鼠,把造模成功的40只大鼠分为3组:模型组(n=12),高剂量组(n=14),低剂量组(n=14)。另加正常组(n=8)。高、低剂量组每天分别给予帕病1号方颗粒18 g/kg,9 g/kg,模型组、正常组均予等体积蒸馏水。32 d后,行旋转测试;测定大鼠左侧纹状体匀浆中超氧化物歧化酶(SOD)活性及谷胱甘肽(GSH)、丙二醛(MDA)含量,免疫组化法检测中脑黑质P-Akt(ser 473)、Bcl-2、Bax表达。结果治疗后,与同期模型组相比,高、低剂量组旋转行为学明显改善(P<0.01),且存在量效关系(P<0.01)。与同期模型组相比,高剂量组SOD活性(P<0.01)和GSH含量明显提高(P<0.01),MDA含量降低(P<0.01);低剂量组GSH含量提高(P<0.01),MDA含量降低(P<0.01);与低剂量相比,高剂量组GSH含量提高(P<0.01),MDA含量降低了(P<0.01)。与模型组相比,高、低剂量组P-Akt(ser 473)、Bcl-2、Bax阳性细胞数及Bc1-2/Bax比值有显著性差异(P<0.05),且存在量效关系(P<0.05)。结论帕病1号方颗粒能提高大鼠抗氧化能力和清除自由基能力,同时激活Akt信号转导通路,发挥其神经保护作用。其神经保护作用呈一定的量效关系。

Objective To explore the neuroprotection of Pabing Formula I Granules for Parkinson＇s disease （PD） rats. Methods PD rats were induced with injection of 6-hydroxy dopamine twice stereotaxically into the left striatum. 40 rats modeled successfully were divided in-to model group （n=12）, high dose group （n=14） and low dose group （n=14）, and the other 8 rats were as normal group. The high dose group and low dose group received Pabing Formula I Granules 18 g/kg and 9 g/kg respectively, while the model group and normal group were giv-en distilled water at the same volume, once a day for 32 d. Then, they were assessed with rotation test. The activities of superoxide dis-mutase （SOD）, the levels of glutathione （GSH） and malonaldehyde （MDA） of their left striatum were measured, and the expression of P-Akt （ser 473）, Bcl-2, and Bax in substantia nigra were detected with immunohistochemistry. Results The rotation released was significant differ-ent among the model, high dose and the low dose groups after treatment （P〈0.01）, with the activities of SOD （P〈0.01） and the content of GSH （P〈0.01） increasing and the content of MDA （P〈0.01） descreasing. There was significant difference in the content of GSH （P〈0.01） and MDA （P〈0.01） between the high and the low dose groups. There was significant difference in expression of P-Akt （ser 473）, Bcl-2 and Bax among the model, high dose and the low dose groups, as well as the Bcl-2/Bad ratio （P〈0.05）. Conclusion Pabing Formula I Granules plays neuroprotective effect through enhancing antioxidation and eliminating free radicals ability and Akt signaling pathway, which appears as dose-effect relationship.