摘要
目的:观察帕病2号方对6-羟基多巴胺(6-OHDA)所致帕金森病(PD)大鼠中脑黑质组织内核因子E2相关性因子2(Nrf2)以及下游靶基因血红加氧酶1(HO-1)的表达。方法:采用6-OHDA左侧纹状体两点注射法建立PD大鼠模型,经阿卟吗啡(APO)诱导表现为恒定右侧旋转且旋转圈数大于210 r·30 min-1视为成功PD大鼠模型。24只造模成功大鼠随机分为模型组,帕病2号方低、中、高剂量组(8.0,16.0,32.0 g·kg-1),同时设立正常组,假手术组。正常组,假手术组,模型组给予等容积蒸馏水,连续灌胃给药4周。Western blot法检测中脑黑质Nrf2细胞核蛋白及HO-1蛋白表达。RT-PCR法检测中脑黑质Nrf2,HO-1mRNA表达。结果:与假手术组比较,模型组Nrf2细胞核蛋白,HO-1蛋白表达上调(P<0.01),Nrf2,HO-1mRNA水平上调(P<0.01);与模型组比较,帕病2号方低、中、高剂量组大鼠中脑黑质组织Nrf2细胞核蛋白,HO-1蛋白表达明显上调(P<0.01),Nrf2,HO-1mRNA水平上调(P<0.01),帕病2号方高剂量组与中、低剂量组比较有明显差异(P<0.01)。结论:6-OHDA造模后可以激活Nrf2/HO-1信号通路;帕病2号方治疗后进一步提高Nrf2细胞核蛋白和Nrf2mRNA表达,进而上调下游靶基因HO-1蛋白及HO-1mRNA的表达,且帕病2号方高剂量组作用更为明显。
Objective：To investigate the effect of Pabing 2 formula on the expression of nuclear factor E2-related factor 2 （Nrf2） and the hemeoxygenasel （HO-1） in substantia nigra tissue of Parkinson disease （PD） rats model induced by 6-hydroxydopamine （6-OHDA）.Method：The rats were stereotaxically injected with 6-OHDA solution into the left striatum in two-site.Rats showed consistently right whirling and the number of rotation was more than 210 r ·30 min-1 induced by APO,then the rat was judged as PD model.Twenty-four modeling rats successfully were randomly divided into four groups：model group,Pabing 2 formula （8.0,16.0,32.0 g · kg-1）,at the same time,the normal group and sham group were established and given distilled water at the same volume,all with a course of 4 weeks.The nuclear Nrf2 protein and HO-1 protein levels of the substantia nigra tissue were detected by Western blot,and the mRNA levels of Nrf2 and HO-1 were determined with RT-PCR.Result：Compared with sham group,the nuclear Nrf2 protein and HO-1 protein in substantia nigra tissue were significant increased （P ＜ 0.01）,and the mRNA levels of Nrf2 and HO-1 were increased in model group （P ＜ 0.01）.Compared with model group,the nuclear Nrf2 protein and HO-1 protein in substantia nigra tissue were significantly increased （P ＜ 0.01）,and the mRNA levels of both Nrf2 and HO-1were also upregulated in Pabing 2 formula low dose group,media dose group and high dose group （P ＜ 0.01）,Pabing 2 formula high dose group were significantly differences compared with the low dose group and media dose group （P ＜0.01）.Conclusion：After 6-OHDA injection,the Nrf2/HO-1 signal transduction pathway is activated.Pabing 2 formula can enhance antioxidation ability.The underlying mechanism might be associated with activating Nrf2/HO-1 signal transduction pathway,promoting the nuclear Nrf2 protein and Nrf2 mRNA,then advancing the expression of antioxidant gene in the downstream such as HO-1 protein and HO-1 mRNA.The effects were more obvious in Pabing 2 formula high dose group.
出处
《中国实验方剂学杂志》
CAS
北大核心
2014年第8期158-162,共5页
Chinese Journal of Experimental Traditional Medical Formulae
基金
广东省中医药管理局项目(20132150)
