Involvement of P2Y12 receptor of stellate ganglion in diabetic cardiovascular autonomic neuropathy
Diabetes as a chronic epidemic disease with obvious symptom of hyperglycemia is seriously affecting human health globally due to the diverse diabetic complications. Diabetic cardiovascular autonomic neuropathy (DCAN) is a common complication of both type 1 and type 2 diabetes and incurs high morbidity and mortality. However, the underlying mechanism for DCAN is unclear. It is well known that purinergic signaling is involved in the regulation of cardiovascular function. In this study, we examined whether the P2Y12 receptor could mediate DCAN-induced sympathetic reflexes. Our results revealed that the abnormal changes of blood pressure, heart rate, heart rate variability, and sympathetic nerve discharge were improved in diabetic rats treated with P2Y12 short hairpin RNA (shRNA). Meanwhile, the expression of P2Y12 receptor, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and connexin 43 (Cx43) in stellate ganglia (SG) was decreased in P2Y12 shRNA-treated diabetic rats. In addition, knocking down the P2Y12 receptor also inhibited the activation of p38 MARK in the SG of diabetic rats. Taken together, these findings demonstrated that P2Y12 receptor in the SG may participate in developing diabetic autonomic neuropathy, suggesting that the P2Y12 receptor could be a potential therapeutic target for the treatment of DCAN.
KeywordsP2Y12 receptor Diabetic cardiovascular autonomic neuropathy Stellate ganglia Satellite glial cells
This study was supported by grants from the National Natural Science Foundation of China (81560219, 31560276, 81570735, and 81200853), a grant from the young scientist training object of Jiangxi Province (20153BCB23030), and a grant from the Natural Science Foundation of Jiangxi Province (20171BAB205025).
Compliance with ethical standards
Conflicts of interest
Jingjing Guo declares that she has no conflict of interest.
Xuan Sheng declares that she has no conflict of interest.
Yu Dan declares that she has no conflict of interest.
Yurong Xu declares that she has no conflict of interest.
Yuanruohan Zhang declares that he has no conflict of interest.
Huihong Ji declares that she has no conflict of interest.
Jiayue Wang declares that she has no conflict of interest.
Zixi Xu declares that she has no conflict of interest.
Hongyu Che declares that she has no conflict of interest.
Guodong Li declares that he has no conflict of interest.
Shangdong Liang declares that he has no conflict of interest.
Guilin Li declares that she has no conflict of interest.
The use of animals was reviewed and approved by the Animal Care and Use Committees of Nanchang University Medical Schools.
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