GanDouLing combined with Penicillamine improves cerebrovascular injury via PERK/eIF2α/CHOP endoplasmic reticulum stress pathway in the mouse model of Wilson's disease
GanDouLing combined with Penicillamine improves cerebrovascular injury via PERK/eIF2α/CHOP endoplasmic reticulum stress pathway in the mouse model of Wilson's disease
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DOI：
10.1042/bsr20180800
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发表时间：
2018-10-31
影响因子：
4
通讯作者：
Yang, Wenming
中科院分区：
文献类型：
--
作者：
Chen, Yonghua;Zhang, Bo;Yang, Wenming
目的探讨肝豆灵联合青霉素对肝豆状核变性（WD）脑血管损伤的作用及机制。ELISA法检测血管损伤因子的表达。HE染色观察脑血管病理改变。免疫组化法检测ICAM-1、VCAM-1和GRP 78的表达。Western blotting检测caspase-3、caspase-12、PERK、eIF 2 α和CHOP的表达。TUNEL法检测细胞凋亡。WD组血管损伤因子及ICAM-1、VCAM-1的表达明显增加，肝豆灵-青霉胺组明显降低。Wilson组caspase-3、caspase-12、PERK、eIF 2 α、CHOP表达明显，肝豆灵-青霉胺能抑制细胞凋亡和内质网应激。提示肝豆灵-青霉胺通过PERK/eIF 2 α/CHOP ER应激通路改善WD小鼠脑血管损伤。
We aim to investigate the function and mechanism of GanDouLing combinated with Penicil-lamine on cerebrovascular injury in Wilson's disease (WD). ELISA was performed to analyze the expression of vascular injury factors. Pathological changes of cerebral vessels were observed by HE stain. Immunohistochemistry assays were performed to analyze the expression of ICAM-1, VCAM-1, and GRP78. Western blotting was measured to analyze the expression of caspase-3, caspase-12, PERK, eIF2 alpha, and CHOP. Apoptosis was detected with TUNEL assay. The expression of vascular injury factors and ICAM-1, VCAM-1 was significantly increased by WD and markedly decreased in GanDouLing-Penicillamine group. The expression of caspase-3, caspase-12, PERK, eIF2 alpha, and CHOP were obviously expressed in Wilson group, GanDouLing-Penicillamine suppressed apoptosis and endoplasmic reticulum (ER) stress. Our findings suggested that GanDouLing-Penicillamine improved cerebrovascular injury through PERK/ eIF2 alpha/CHOP ER stress pathway in the mouse model of WD.