Investigation on the protective effect of Arisaema Cum Bile<italic style="font-style: italic"> </italic>on MPTP-induced Parkinson’s disease model mice based on PKA signaling pathway

CHEN Guien; DENG Yafang; DENG Wanrou; WU Binxi; PENG Donghui; ZENG Yuanning; WANG Qiuhong

doi:10.6039/j.issn.1001-0408.2023.15.04

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Investigation on the protective effect of Arisaema Cum Bile on MPTP-induced Parkinson’s disease model mice based on PKA signaling pathway

更新时间：2023-08-10

- Investigation on the protective effect of Arisaema Cum Bile on MPTP-induced Parkinson’s disease model mice based on PKA signaling pathway
- ZHONGGUO YAOFANG Vol. 34, Issue 15, Pages: 1809-1814(2023)
- 作者机构：
  
  1.广东药科大学中药学院/广东省中药饮片规范化炮制工程技术研究中心，广州　510006
  2.黑龙江中医药大学教育部北药基础与应用研究重点实验室/黑龙江省中药及天然药物药效物质基础研究重点实验室，哈尔滨　150040
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.15.04
  CLC： R285;R965
- Published：15 August 2023，
  
  Received：30 January 2023，
  
  Revised：18 June 2023，
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陈桂恩,邓雅方,邓婉柔等.基于PKA信号通路探讨胆南星对MPTP诱导帕金森病模型小鼠的保护作用 ^Δ[J].中国药房,2023,34(15):1809-1814.

CHEN Guien,DENG Yafang,DENG Wanrou,et al.Investigation on the protective effect of Arisaema Cum Bileon MPTP-induced Parkinson’s disease model mice based on PKA signaling pathway[J].ZHONGGUO YAOFANG,2023,34(15):1809-1814.
陈桂恩,邓雅方,邓婉柔等.基于PKA信号通路探讨胆南星对MPTP诱导帕金森病模型小鼠的保护作用 ^Δ[J].中国药房,2023,34(15):1809-1814. DOI： 10.6039/j.issn.1001-0408.2023.15.04.

CHEN Guien,DENG Yafang,DENG Wanrou,et al.Investigation on the protective effect of Arisaema Cum Bileon MPTP-induced Parkinson’s disease model mice based on PKA signaling pathway[J].ZHONGGUO YAOFANG,2023,34(15):1809-1814. DOI： 10.6039/j.issn.1001-0408.2023.15.04.

摘要

目的

探讨胆南星对帕金森病（PD）模型小鼠的改善作用及可能机制。

方法

将60只雄性C57BL/6J小鼠随机分为正常组、模型组、胆南星低剂量组[0.39 g/（kg·d）]、胆南星高剂量组[1.56 g/（kg·d）]和阳性对照药左旋多巴片组[80 mg/（kg·d）]，每组12只。除正常组小鼠注射等体积生理盐水外，其余各组连续5 d腹腔注射1-甲基-4-苯基-1，2，3，6-四氢吡啶[MPTP，35 mg/（kg·d）]建立亚急性PD模型；造模完成后连续给药治疗7 d，于造模前1 d、造模第5天和末次给药后进行爬杆实验和线悬挂测试。采用免疫荧光法检测小鼠脑黑质中酪氨酸羟化酶（TH）阳性神经元数量；采用酶联免疫吸附法检测小鼠血清中白细胞介素1β（IL-1β）和肿瘤坏死因子α（TNF-α）水平以及脑黑质中IL-1β、TNF-α、环氧合酶2（COX-2）和诱导型一氧化氮合酶（iNOS）水平；采用Western blot法检测小鼠脑黑质中cAMP依赖的蛋白激酶催化亚单位α（PKA C-α）、谷胱甘肽过氧化物酶4（GPX4）以及铁蛋白重链多肽1（FTH1）蛋白的表达。

结果

末次给药后，与正常组比较，模型组小鼠爬杆时间显著延长（

＜0.01），线悬挂评分显著降低（

＜0.01），脑黑质中TH阳性神经元数量显著减少（

＜0.01），血清中IL-1β、TNF-α水平和脑黑质中IL-1β、TNF-α、COX-2、iNOS水平显著升高（

＜0.01），脑黑质中GPX4、PKA C-α和FTH1蛋白表达水平显著降低（

＜0.05或

＜0.01）。与模型组比较，胆南星高剂量组小鼠上述指标水平均显著回调（

＜0.05或

＜0.01）。

结论

胆南星能够改善MPTP诱导的PD模型小鼠运动能力障碍，减少脑黑质TH神经元死亡，对模型小鼠具有神经保护作用；这可能与其激活PKA信号通路来抑制神经炎症和神经元细胞铁死亡有关。

Abstract

OBJECTIVE

To investigate the improvement effects of Arisaema Cum Bile on Parkinson’s disease （PD） model mice and its potential mechanism.

METHODS

Sixty male C57BL/6J mice were randomly divided into normal group， model group， Arisaema Cum Bile low-dose group [0.39 g/（kg·d）]， Arisaema Cum Bile high-dose group [1.56 g/（kg·d）] and positive control drug Levodopa tablet group [80 mg/（kg·d）]， with 12 mice in each group. Except that normal group was given constant volume of normal saline， other groups were given 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine [MPTP，35 mg/（kg·d）] intraperitoneally for 5 consecutive days to induce subacute PD model； after modeling， they were given relevant medicine continuously for 7 d； rod climbing test and line suspension test were performed 1 d before modeling， on the 5th day of modeling and after the last medication. The number of tyrosine hydroxylase （TH）-positive neurons in the substantia nigra of mice were measured by immunofluorescence； the levels of interleukin 1β （IL-1β） and tumor necrosis factor α （TNF-α） in serum and the levels of IL-1β， TNF-α， cyclooxygenase-2 （COX-2） and inducible nitric oxide synthase （iNOS） in the substantia nigra of mice were measured by enzyme-linked immunosorbent assay. The expression levels of cAMP-dependent protein kinase catalytic subunit α （PKA C-α）， glutathione peroxidase 4 （GPX4） and ferritin heavy chain polypeptide 1 （FTH1） proteins in the substantia nigra of mice was measured by Western blot.

RESULTS

After last medicine， compared with the normal group， mice in the model group had significantly longer pole-climbing time （

＜0.01）， significantly lower line suspension scores （

＜0.01）， significantly fewer TH-positive neurons in the substantia nigra （

＜0.01）， significantly higher serum concentrations of IL-1β and TNF-α and nigrostriatal concentrations of IL-1β， TNF-α， COX-2 and iNOS （

＜0.01）， while lower protein expression levels of GPX4， PKA C-α and FTH1 in the substantia nigra （

＜0.05 or

＜0.01）. Compared with the model group， the above indexes of mice were significantly returned in Arisaema Cum Bile high-dose group （

＜0.05 or

＜0.01）.

CONCLUSIONS

Arisaema Cum Bile can improve motor impairment and reduce apoptosis of nigrostriatal TH neurons in MPTP-induced PD mice， and has neuroprotective effects on model mice； this may be related to its inhibition of neuroinflammation and the inhibition of ferroptosis by up-regulating PKA signaling pathway.

关键词

胆南星帕金森病1-甲基-4-苯基-1，2，3，6-四氢吡啶cAMP依赖的蛋白激酶信号通路神经炎症铁死亡

Keywords

Parkinson’s disease1-methyl-4-phenyl-1，2，3，6-tetrahydropyridinecAMP-dependent protein kinase signaling pathwayneuroinflammationferroptosis

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Investigation on the protective effect of Arisaema Cum Bile on MPTP-induced Parkinson’s disease model mice based on PKA signaling pathway

DOI：10.6039/j.issn.1001-0408.2023.15.04

摘要

Abstract

关键词

Keywords

references