Glucokinase in stellate ganglia cooperates with P2X3 receptor to develop cardiac sympathetic neuropathy in type 2 diabetes rats

被引:17
作者
Xu, Xiumei [1 ,2 ]
Liu, Baoe [3 ]
Yang, Jingjian [3 ]
Zou, Yuting [3 ]
Sun, Minghao [3 ]
Li, Zijing [3 ]
Lin, Li [1 ,2 ]
Yang, Runan [1 ,2 ]
Zou, Lifang [1 ,2 ]
Li, Guilin [1 ,2 ]
Liu, Shuangmei [1 ,2 ]
Li, Guodong [1 ,2 ]
Liang, Shangdong [1 ,2 ]
机构
[1] Nanchang Univ, Basic Med Coll, Physiol Dept, Neuropharmacol Lab, Nanchang 330006, Jiangxi, Peoples R China
[2] Jiangxi Prov Key Lab Auton Nervous Funct & Dis, Nanchang 330006, Jiangxi, Peoples R China
[3] Nanchang Univ, Undergrad Student Med Coll, Nanchang 330006, Jiangxi, Peoples R China
基金
中国国家自然科学基金;
关键词
Glucokinase; P2X3; receptor; Stellate ganglia; Diabetic cardiac sympathy; P2X(3) RECEPTOR; MYOCARDIAL-ISCHEMIA; EXPRESSION;
D O I
10.1016/j.brainresbull.2020.10.004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Glucokinase (GCK) may be involved in inflammatory pathological changes, while the P2X3 receptor in the stellate ganglia (SG) is related to diabetic cardiac autonomic neuropathy. In this study, we explored the relationship between the upregulated GCK in SG and diabetic cardiac sympathy. The expression and location of GCK and P2X3 in SG of type 2 diabetes mellitus (T2DM) rats were assessed. Changes in cardiac function were determined by measuring blood pressure, sympathetic nerve activity, heart rate, and heart rate variability. P2X3 agonist-activated currents in isolated stellate ganglion neurons and cultured human embryonic kidney 293 (HEK293) cells were recorded using whole-cell patch clamp techniques. The upregulated expression of GCK in SG of T2DM rats was decreased after treatment with GCK short hairpin RNA (shRNA). GCK shRNA treatment also improved the blood pressure, sympathetic nerve activity, heart rate, and heart rate variability in T2DM rats. By contrast, the expression of P2X3 and tumor necrosis factor alpha (TNF-alpha) was lessened by GCK shRNA treatment. In addition, adenosine triphosphate (ATP)-activated currents in stellate ganglion neurons and HEK293 cells cotransfected with GCK and P2X3 receptor plasmids were reduced after GCK shRNA treatment. In T2DM rats, knockdown of GCK relieved the diabetic cardiac sympathy mediated by P2X3 receptor-involved upregulation of GCK in SG.
引用
收藏
页码:290 / 297
页数:8
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