摘要
目的探讨人参皂苷Rg1对帕金森病(PD)小鼠中脑黑质中神经调节蛋白1(NRG1)-Erb B4信号通路活性的影响。方法将40只C57BL/6小鼠随机分为生理盐水对照组、1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)模型组、MPTP+Rg1组、MPTP+Rg1+N-[2-(P-溴苯丙烯盐基氨基)乙基]-5-异喹啉磺酰胺(H89)组。在注射MPTP前3 d,生理盐水对照组、MPTP模型组小鼠腹腔注射生理盐水1 m L·kg-1·d-1,MPTP+Rg1组、MPTP+Rg1+H89组小鼠腹腔注射人参皂苷Rg1 10 mg·kg-1·d-1,连续4 d,第4天在注射完人参皂苷2 h后,MPTP模型组、MPTP+Rg1组、MPTP+Rg1+H89组小鼠腹腔注射MPTP 20 mg·kg-1,均注射4次,每次间隔2 h,而MPTP+Rg1+H89组在首次注射MPTP前30 min腹腔注射H89 1 mg·kg-1。药物注射后连续7 d观察小鼠行为学变化,采用反转录多聚酶链反应(RT-PCR)检测小鼠中脑黑质中Nrg1与Erb B4基因的mRNA表达情况,采用Western blot检测NRG1受体Erb B4蛋白及磷酸化Erb B4(p-Erb B4)蛋白的表达及其磷酸化水平。结果 MPTP模型组小鼠中脑黑质内Nrg1基因mRNA表达水平低于生理盐水对照组(P=0.007 9)和MPTP+Rg1组(P=0.004 9);MPTP+Rg1+H89组与MPTP模型组相比,Nrg1 mRNA表达水平差异无统计学意义(P=0.151 3);MPTP+Rg1+H89组与MPTP+Rg1组比较,小鼠中脑黑质内Nrg1 mRNA表达水平降低(P=0.049 3)。MPTP模型组小鼠中脑黑质内的Nrg1-typeⅠ/Ⅱ的mRNA表达水平显著低于生理盐水对照组(P=0.001 9)和MPTP+Rg1组(P=0.043 2);MPTP+Rg1+H89组与MPTP模型组小鼠中脑黑质内Nrg1-typeⅠ/ⅡmRNA表达水平比较差异无统计学意义(P=0.688 5);MPTP+Rg1+H89组与MPTP+Rg1组比较,小鼠中脑黑质内Nrg1-typeⅠ/ⅡmRNA表达显著下降(P=0.029 4)。与生理盐水对照组相比,Nrg1-typeⅢmRNA在MPTP组略有降低,但差异无统计学意义(P=0.290 8);与MPTP模型组比较,MPTP+Rg1组小鼠中脑黑质内Nrg1-typeⅢmRNA表达升高(P=0.041 9),MPTP+Rg1+H89组小鼠黑质Nrg1-typeⅢmRNA表达降低(P=0.728 9);MPTP+Rg1+H89组与MPTP+Rg1组小鼠黑质Nrg
Objective To explore the effect of ginsenoside Rg1 on neuregulin1( NRG1)-Erb B4 signal pathway in substantia nigra of midbrain in Parkinson's diseases( PD) model mouse. Methods Forty C57 BL /6 mice were randomly divided into physiological saline control group,1-methy-4-pheny-1,2,3,6-tetrahy-dropyrdine( MPTP) group,MPTP + Rg1 group,MPTP + Rg1 + N-[2-[[3-( 4-bromophenyl)-2-propen-1-yl]amino]ethyl]( H89) group,with ten mice in each group. At three days before injecting MPT,the mice in physiological saline control group and MPTP group were given intraperitoneal injection of physiological saline 1 m L·kg- 1·d- 1; the mice in MPTP + Rg1 group and MPTP + Rg1 + H89 were given intraperitoneal injection of ginsenoside Rg1 10 mg·kg- 1·d- 1for four days. On the fourth day,at the tow hours after injecting ginsenoside,the mice in MPTP model group,MPTP + Rg1 group and MPTP + Rg1 + H89 group were given intraperitoneal injection of MPTP20 mg·kg- 1for four times at intervals of 2 h; while the mice in MPTP + Rg1 + H89 group were given intraperitoneal injection of H89 1 mg·kg- 1at 30 min before injecting MPTP. The ethology change of mice were observed after administration of drugs for 7-consecutive-day. Reverse transcription-polymerase chain reaction was used to detected the Nrg1 and Erb B4 mRNA expression in substantia nigra of midbrain of mice; Western blotting was used to detect the expression levels of Erb B4 protein and phosphorylation Erb B4( p-Erb B4) protein. Results The expression of Nrg1 mRNA in substantia nigra of midbrain of mice in MPTP model group was significantly lower than that in physiological saline control group( P = 0. 007 9) and MPTP + Rg1group( P = 0. 004 9); there was no statistic difference of Nrg1 mRNA expression between MPTP + Rg1 + H89 group and MPTP model group( P = 0. 151 3); the expression of Nrg1 mRNA in substantia nigra of midbrain of mice in MPTP + Rg1 + H89 group was significantly lower than that in MPTP + Rg1 group( P
出处
《新乡医学院学报》
CAS
2016年第4期275-280,共6页
Journal of Xinxiang Medical University
基金
河南省高校科技创新人才支持计划资助项目(编号:2010HASTTT008)