[1]李苗苗,王淑秀.人参皂苷Rg1对帕金森病小鼠中脑黑质神经调节蛋白1-ErbB4信号通路活性的影响[J].新乡医学院学报,2016,33(4):275-280.[doi:10.7683/xxyxyxb.2016.04.007]
　LI Miao-miao,WANG Shu-xiu.Effect of ginsenoside Rg1 on activity of neuregulin1-ErbB4 signal pathway in substantia nigra of midbrain in Parkinson′s disease model mouse[J].Journal of Xinxiang Medical University,2016,33(4):275-280.[doi:10.7683/xxyxyxb.2016.04.007]
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人参皂苷Rg1对帕金森病小鼠中脑黑质神经调节蛋白1-ErbB4信号通路活性的影响
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
33
期数:
2016年4
页码:
275-280
栏目:
基础研究
出版日期:
2016-04-06

文章信息/Info

Title:
Effect of ginsenoside Rg1 on activity of neuregulin1-ErbB4 signal pathway in substantia nigra of midbrain in Parkinson′s disease model mouse
作者:
李苗苗1; 2; 王淑秀1
(1.新乡医学院基础医学院病理学教研室，河南　新乡　453003；2.新乡市第一人民医院病理科，河南　新乡　453000）
Author(s):
LI Miao-miao1; 2; WANG Shu-xiu1
(1.Department of Pathology,School of Basic Medical Sciences,Xinxiang Medical University,Xinxiang 453003，Henan Province,China；2.Department of Pathology,the First People′s Hospital of Xinxiang City,Xinxiang 453000,Henan Province,China)
关键词:
帕金森病; 人参皂苷Rg1; 神经调节蛋白1; ErbB4
Keywords:
Parkinson′s diseases; ginsenoside Rg1; neuregulin1; ErbB4
分类号:
R741
DOI:
10.7683/xxyxyxb.2016.04.007
文献标志码:
A
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）-ErbB4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 mL·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ErbB4基因的mRNA表达情况，采用Western blot检测NRG1受体ErbB4蛋白及磷酸化ErbB4（p-ErbB4）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-type Ⅰ/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-type Ⅰ/Ⅱ mRNA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-type Ⅰ/Ⅱ mRNA表达显著下降（P=0.029 4）。与生理盐水对照组相比，Nrg1-type Ⅲ mRNA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-type Ⅲ mRNA表达升高（P=0.041 9），MPTP+Rg1+H89组小鼠黑质Nrg1-type Ⅲ mRNA表达降低（P=0.728 9）；MPTP+Rg1+H89组与MPTP+Rg1组小鼠黑质Nrg1-type Ⅲ mRNA表达比较差异无统计学意义（P=0.164 2）。生理盐水对照组、MPTP模型组、MPTP+Rg1组、MPTP+Rg1+H89组小鼠黑质ErbB4 mRNA表达水平比较差异均无统计学意义（P=0.531 8）。各组小鼠中脑黑质内ErbB4蛋白表达水平比较差异均无统计学意义（P=0.800 5）；MPTP模型组小鼠黑质内 p-ErbB4蛋白表达水平低于生理盐水对照组（P=0.013 4）和 MPTP+Rg1组（P=0.019 9）；MPTP+Rg1+H89组p-ErbB4蛋白表达水平低于MPTP+Rg1组（P=0.047 8）；MPTP+Rg1+H89组与MPTP模型组p-ErbB4表达水平比较差异无统计学意义（P=0.887 7）。结论　PD小鼠脑内的NRG1基因表达及其ErbB4受体的活性降低，而人参皂苷Rg1可能通过增强小鼠中脑黑质NRG1-ErbB4的通路活性而改善PD的症状。
Abstract:
Objective　To explore the effect of ginsenoside Rg1 on neuregulin1（NRG1）-ErbB4 signal pathway in substantia nigra of midbrain in Parkinson′s diseases (PD) model mouse.Methods　Forty C57BL/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 mL·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-1 for 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 MPTP 20 mg·kg-1 for four times at intervals of 2 h;while the mice in MPTP+Rg1+H89 group were given intraperitoneal injection of H89 1 mg·kg-1 at 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 ErbB4 mRNA expression in substantia nigra of midbrain of mice;Western blotting was used to detect the expression levels of ErbB4 protein and phosphorylation ErbB4(p-ErbB4) 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+Rg1 group(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=0.049 3）.The expression of Nrg1-type Ⅰ/Ⅱ mRNA in substantia nigra of midbrain of mice in MPTP model group was significantly lower than that in physiological saline control group (P=0.001 9) and MPTP+Rg1 group（P=0.043 2）；there was no statistic difference of Nrg1-type Ⅰ/Ⅱ mRNA expression between the MPTP+Rg1+H89 group and MPTP model group（P= 0.688 5）；the expression of Nrg1-type Ⅰ/Ⅱ mRNA in MPTP+Rg1+H89 group was significantly lower than that in MPTP+Rg1 group（P=0.029 4）.There was no statistic difference of Nrg1-type Ⅲ mRNA expression between physiological saline control group and MPTP model group（P=0.290 8）；the expression of Nrg1-type Ⅲ mRNA in MPTP+Rg1 group was significantly higher than that in MPTP model group（P=0.041 9）；the expression of Nrg1-type Ⅲ mRNA in substantia nigra of midbrain of mice in MPTP+Rg1+H89 group was significantly lower than that in MPTP model group（P=0.728 9）；there was no statistic difference of Nrg1-type Ⅲ mRNA expression in substantia nigra of midbrain of mice between the MPTP+Rg1+H89 group and MPTP+Rg1group（P=0.164 2）.There was no statistic difference of ErbB4 mRNA expression in substantia nigra of mice among physiological saline control group,MPTP model group,MPTP+Rg1 group and MPTP+Rg1+H89 group（P=0.531 8）.There was no statistic difference of ErbB4 protein expression in substantia nigra of mice among physiological saline control group,MPTP model group,MPTP+Rg1 group and MPTP+Rg1+H89 group（P=0.800 5）；the expression of p-ErbB4 protein in substantia nigra of mice in MPTP model group was significantly lower than that in physiological saline control group （P=0.013 4）and MPTP+Rg1 group（P=0.019 9）;the expression of p-ErbB4 protein in substantia nigra of mice in MPTP+Rg1+H89 group was significantly lower than that in MPTP+Rg1 group（P=0.047 8）；there was no statistic difference of the expression of p-ErbB4 protein between the MPTP+Rg1+H89 group and MPTP model group（P=0.887 7）.Conclusion　Nrg1 gene expression and the activation of ErbB4 are decreased in brain of PD model mice;ginsenoside Rg1 can improve the symptoms of PD by hyperenhancementing the activation of NRG1-ErbB4 signal pathway.

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更新日期/Last Update: 2016-04-05