摘要
目的观察由鱼藤酮制备的帕金森病(PD)大鼠模型黑质多巴胺能神经元中氧化应激参数、转录因子NF-E2相关因子(Nrf2)及其基因产物血红素氧合酶1(HO-1)和依赖还原型辅酶/Ⅱ醌氧化还原酶1(NQO1)的表达变化情况。方法将健康成年雄性Wistar大鼠40只随机分为对照组和实验组,20只对照组大鼠给予背部皮下注射葵花油[1 m L/(kg·d)],20只实验组大鼠,按照2.0 mg/(kg·d)背部皮下注射鱼藤酮(鱼藤酮溶解在葵花籽油中)制备PD大鼠模型,共30 d。最后一次注射结束后实验大鼠迅速断头取材,采用分光光度法检测大鼠脑内纹状体中丙二醛(MDA)和还原型谷胱甘肽(GSH)含量变化,采用Western blot检测两组大鼠中脑黑质中Nrf2、HO-1和NQO1的表达。结果对照组和实验组脑内纹状体中MDA含量分别为(6.51±1.45)、(18.13±2.14)nmol/mgprot,与对照组比较,实验组大鼠纹状体中MDA升高了64.09%(P<0.01)。对照组和实验组纹脑内状体中GSH含量分别为(44.53±4.71)、(26.41±2.52)mg/gprot,与对照组比较,实验组大鼠纹状体中GSH降低了40.69%(P<0.01)。对照组大鼠中脑黑质中Nrf2、HO-1和NQO1与β-actin免疫印迹条带相对吸光度比值分别为(0.81±0.05)、(0.84±0.07)和(0.91±0.15),实验组大鼠中脑黑质中Nrf2、HO-1和NQO1与β-actin免疫印迹条带相对吸光度比值分别为(0.42±0.06)、(0.49±0.03)和(0.33±0.04)。与对照组比较,实验组大鼠黑质神经元中Nrf2、HO-1和NQO1表达分别降低了48.15%、41.67%和63.74%(P<0.01)。结论氧化应激在PD发病中起着非常重要的作用,内源性抗氧化损伤通路Nrf2-ARE与PD的发病关系密切,可能是PD新的治疗靶点。
Objective To study the change of the expression oxidative about stress parameters, transcription factor NF-E2-related factor （Nrf2） and two Nrf2-regulated gene products, heme oxygenase-1 （HO-1） and NAD （P） H：quinone oxidoreductase-1 （NQO1） in the substantia nigra of Parkinson＇s disease （PD） rats induced by Rotenone. Meth-ods 40 healthy adult male Wistar rats were randomly divided into control group and experimental group, with 20 rats in each group. The rats of control group only were injected subcutaneously sunflower oil in back [1 mL/（kg·d）], the rats of experimental group were injected subcutaneously rotenone [（2.0 mg/（kg·d） ] in back to prepare the PD rats model （Rotenone dissolved in sunflower oil）, A total of 30 days. After the last injection, the rats were decollated quickly, Spectrophotometry were used to detect oxidative stress parameters （malondialdehyde and glutathione）, Western blot were used to detect the changed expression of Nrf2, HO-1 and NQO1 in the substantia nigra of rats in two groups. Results The MDA content in brain striatum of control group and experimental group were （6.51±1.45）, （18.13±2.14） nmol/mg-prot, respectively. Compared with the control group, the MDA of experimental group increased by 64.09% （P〈 0.01）. The GSH content in brain striatum of control group and experimental group were （44.53±4.71）, （26.41±2.52） mg/gprot, respectively. Compared with the control group, the MDA of experimental group decreased by 40.69% （P〈 0.01）. The immunoblot of Nrf2, HO-1 and NQO1 in the rats midbrain nigra of the control group were （0.81±0.05）, （0.84±0.07） andnbsp;（0.91±0.15）, respectively. The immunoblot of Nrf2, HO-1 and NQO1 in the rats midbrain nigra of the experi-mental group were （0.42±0.06）, （0.49±0.03） and （0.33±0.04）, respectively. Compared with the control group, the expres-sion of Nrf2, HO-1 and NQO1 were reduced by 48.15%, 41.67% and 63.74% respectively （P〈 0.01）. Conclusion Ox-
出处
《中国医药导报》
CAS
2014年第35期8-11,共4页
China Medical Herald
基金
河北省科技厅科技计划项目(编号132777134)
