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CLC number: R781.6+4

On-line Access: 2020-03-02

Received: 2019-07-29

Revision Accepted: 2019-10-25

Crosschecked: 2020-02-04

Cited: 0

Clicked: 2012

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Lan Xu

https://orcid.org/0000-0002-4542-5796

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Journal of Zhejiang University SCIENCE B 2020 Vol.21 No.2 P.155-165

http://doi.org/10.1631/jzus.B1900456


Spinal P2X7R contributes to streptozotocin-induced mechanical allodynia in mice


Author(s):  Cheng-ming Ni, He-ping Sun, Xiang Xu, Bing-yu Ling, Hui Jin, Yu-qiu Zhang, Zhi-qi Zhao, Hong Cao, Lan Xu

Affiliation(s):  Department of Endocrinology, the Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi 214023, China; more

Corresponding email(s):   hongcao@fudan.edu.cn, xulan126@126.com

Key Words:  P2X7 receptor (P2X7R), Mechanical allodynia, Streptozotocin, Diabetic mice


Cheng-ming Ni, He-ping Sun, Xiang Xu, Bing-yu Ling, Hui Jin, Yu-qiu Zhang, Zhi-qi Zhao, Hong Cao, Lan Xu. Spinal P2X7R contributes to streptozotocin-induced mechanical allodynia in mice[J]. Journal of Zhejiang University Science B, 2020, 21(2): 155-165.

@article{title="Spinal P2X7R contributes to streptozotocin-induced mechanical allodynia in mice",
author="Cheng-ming Ni, He-ping Sun, Xiang Xu, Bing-yu Ling, Hui Jin, Yu-qiu Zhang, Zhi-qi Zhao, Hong Cao, Lan Xu",
journal="Journal of Zhejiang University Science B",
volume="21",
number="2",
pages="155-165",
year="2020",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1900456"
}

%0 Journal Article
%T Spinal P2X7R contributes to streptozotocin-induced mechanical allodynia in mice
%A Cheng-ming Ni
%A He-ping Sun
%A Xiang Xu
%A Bing-yu Ling
%A Hui Jin
%A Yu-qiu Zhang
%A Zhi-qi Zhao
%A Hong Cao
%A Lan Xu
%J Journal of Zhejiang University SCIENCE B
%V 21
%N 2
%P 155-165
%@ 1673-1581
%D 2020
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1900456

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T1 - Spinal P2X7R contributes to streptozotocin-induced mechanical allodynia in mice
A1 - Cheng-ming Ni
A1 - He-ping Sun
A1 - Xiang Xu
A1 - Bing-yu Ling
A1 - Hui Jin
A1 - Yu-qiu Zhang
A1 - Zhi-qi Zhao
A1 - Hong Cao
A1 - Lan Xu
J0 - Journal of Zhejiang University Science B
VL - 21
IS - 2
SP - 155
EP - 165
%@ 1673-1581
Y1 - 2020
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1900456


Abstract: 
Painful diabetic neuropathy (PDN) is a diabetes mellitus complication. Unfortunately, the mechanisms underlying PDN are still poorly understood. Adenosine triphosphate (ATP)-gated p2X7 receptor (P2X7R) plays a pivotal role in non-diabetic neuropathic pain, but little is known about its effects on streptozotocin (STZ)-induced peripheral neuropathy. Here, we explored whether spinal cord P2X7R was correlated with the generation of mechanical allodynia (MA) in STZ-induced type 1 diabetic neuropathy in mice. MA was assessed by measuring paw withdrawal thresholds and western blotting. Immunohistochemistry was applied to analyze the protein expression levels and localization of P2X7R. STZ-induced mice expressed increased P2X7R in the dorsal horn of the lumbar spinal cord during MA. Mice injected intrathecally with a selective antagonist of P2X7R and P2X7R knockout (KO) mice both presented attenuated progression of MA. Double-immunofluorescent labeling demonstrated that P2X7R-positive cells were mostly co-expressed with Iba1 (a microglia marker). Our results suggest that P2X7R plays an important role in the development of MA and could be used as a cellular target for treating PDN.

脊髓P2X7受体参与链脲佐菌素诱导的小鼠糖尿病早期机械痛性神经病变

目的:探讨嘌呤能离子通道型受体7(P2X7R)在链脲佐菌素(STZ)诱导的1型糖尿病(T1DM)小鼠早期发生的机械痛性神经病变中的作用.
创新点:探讨脊髓P2X7R在T1DM产生痛性神经病变的早期阶段所起的作用,将有望为研究糖尿病痛性神经病变药物提供新的靶点.
方法:本实验采用健康雄性C57BL小鼠与P2X7R KO小鼠(体重20~23克,从20点至次日8点隔夜禁食12小时)为研究对象,连续三天腹腔注射STZ(浓度为100 mg/kg),从而制备T1DM动物模型.如果空腹血糖>11.1 mmol/L且三周后小鼠机械痛阈值明显下降,则表示模型制备成功.在小鼠机械痛阈下降的对应时间点,取腰段脊髓背角,采用蛋白质印迹法(western blot)和免疫组化方法测定P2X7R的表达情况.同时,在发生机械痛阈值下降的第3周时间鞘内给予其拮抗剂A740003,并进行机械刺激从而观察其痛阈值的变化.
结论:STZ诱导的T1DM动物模型在早期表现为显著的机械诱发痛,并伴随脊髓背角P2X7R表达上调;在痛阈下降期鞘内给予其拮抗剂A740003可抑制糖尿病小鼠的痛行为.与腹腔注射STZ形成T1DM的C57BL/6小鼠相比,P2X7R基因敲除的糖尿病小鼠早期机械痛阈值下降的时间延迟,程度减轻.因此,我们推测P2X7R可能参与了STZ诱导的糖尿病小鼠早期机械痛性神经病变.

关键词:嘌呤能离子通道型受体7(P2X7R);机械痛;链脲佐菌素;糖尿病小鼠

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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