Congrong Shujing Granule-Induced GRP78 Expression Reduced Endoplasmic Reticulum Stress and Neuronal Apoptosis in the Midbrain in a Parkinson's Disease Rat Model.
Congrong Shujing Granule-Induced GRP78 Expression Reduced Endoplasmic Reticulum Stress and Neuronal Apoptosis in the Midbrain in a Parkinson's Disease Rat Model.
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从容舒经颗粒诱导GRP78表达减少帕金森病大鼠模型中脑内质网应激和神经元凋亡
DOI：
10.1155/2020/4796236
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Cai J
中科院分区：
文献类型：
--
作者：
Xu Q;Yang S;Wu F;Lin Y;Zhong J;Tang L;Hu X;Cai J
帕金森病（PD）的主要病理改变是中脑多巴胺能神经元的变性和丢失以及路易体的形成。许多研究表明，PD的发病机制与内质网（ER）氧化应激密切相关。本研究采用多种中药配伍制备苁蓉舒经颗粒。通过在体外SH-SY 5 Y细胞中的实验干预来确定成分的最佳剂量组合。腹腔注射鱼藤酮向日葵油乳剂建立PD大鼠模型。分别于造模后第14天和CSG干预后第14天（5.88 g/kg、11.76 g/kg和23.52 g/kg）进行悬浮试验。我们评估了运动功能的变化和神经元细胞功能标记蛋白、ER应激（ERS）标记蛋白和神经元细胞凋亡相关通路蛋白的表达。电镜观察细胞超微结构的变化。我们的研究结果表明，CSG治疗延长了PD大鼠对钢丝的抓握时间。与模型组相比，治疗14 d后，CSG中、高剂量组黑质78 kDa葡萄糖调节蛋白（GRP 78）表达明显上调。多巴胺能神经元关键功能酶酪氨酸羟化酶（TH）和脑多巴胺神经营养因子（CDNF）的表达升高。c-Jun N-末端激酶（JNK）和磷酸化c-Jun表达减少，细胞凋亡明显减少。与模型组相比，治疗组ER断裂和脱颗粒（核糖体脱落）较少，ER和线粒体丰富，提示CSG通过诱导分子伴侣GRP 78的表达，减轻了PD大鼠模型中脑的ER应激和神经元凋亡。
The main pathological changes inherent in Parkinson's disease (PD) are degeneration and loss of dopamine neurons in the midbrain and formation of Lewy bodies. Many studies have shown that the pathogenesis of PD is closely related to endoplasmic reticulum (ER) oxidative stress. This study combined various traditional Chinese medicines to prepare Congrong Shujing granules (CSGs). The optimal dose combination of the ingredients was identified by experimental intervention in SH-SY5Y cells in vitro. A PD rat model was established by intraperitoneal injection of rotenone sunflower oil emulsion. The suspension tests were performed on the 14th day after modeling and also on the 14th day after CSG intervention (5.88 g/kg, 11.76 g/kg, and 23.52 g/kg). We evaluated the changes in motor function and the expression of neuronal cell functional marker proteins, ER stress (ERS) marker proteins, and apoptosis-related pathway proteins of neuronal cells. Changes in cellular ultrastructure were observed by electron microscopy. Our results showed that CSG treatment lengthened the duration of PD rats' gripping to the wire. 78 kDa glucose-regulated protein (GRP78) expression in the substantia nigra was significantly upregulated in the middle- and high-dose CSG groups after 14 days of treatment compared with the model group. The expression of the key dopaminergic neuron functional enzyme tyrosine hydroxylase (TH) and cerebral dopamine neurotrophic factor (CDNF) was elevated. The expression of c-Jun N-terminal kinase (JNK) and phosphorylated c-Jun decreased, and cell apoptosis was significantly reduced. Compared with the model group, the treatment groups had fewer ER fragmentation and degranulation (ribosome shedding) and abundant ER and mitochondria suggesting that CSG reduced ER stress and neuronal apoptosis in the midbrain of a PD rat model by inducing the expression of molecular chaperone GRP78.
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影响因子：
4.4
作者：
Ning, Baile;Deng, Minzhen;Fang, Yongqi
通讯作者：
Fang, Yongqi
影响因子：
15.9
作者：
Selvaraj, Senthil;Sun, Yuyang;Singh, Brij B.
通讯作者：
Singh, Brij B.
影响因子：
6.4
作者：
Virachit, Sophie;Mathews, Kathryn J.;Double, Kay L.
通讯作者：
Double, Kay L.
影响因子：
4.3
作者：
Richman C;Rashid S;Prashar S;Mishra R;Selvaganapathy PR;Gupta BP
通讯作者：
Gupta BP
DOI：
10.1016/j.bbamcr.2018.08.012
发表时间：
2018-11-01
影响因子：
5.1
作者：
Arancibia, Duxan;Zamorano, Pedro;Estela Andres, Maria
通讯作者：
Estela Andres, Maria