Involvement of P2Y12 receptor of stellate ganglion in diabetic cardiovascular autonomic neuropathy
Involvement of P2Y12 receptor of stellate ganglion in diabetic cardiovascular autonomic neuropathy
复制标题
星状神经节 P2Y12 受体参与糖尿病心血管自主神经病变。
DOI：
10.1007/s11302-018-9616-5
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发表时间：
2018-12-01
影响因子：
3.5
通讯作者：
Li, Guilin
中科院分区：
文献类型：
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作者：
Guo, Jingjing;Sheng, Xuan;Li, Guilin
糖尿病作为一种以高血糖为明显症状的慢性流行病，其并发症多样，严重影响全球人类健康。糖尿病心血管自主神经病变 (DCAN) 是 1 型和 2 型糖尿病的常见并发症，发病率和死亡率很高。然而，DCAN 的基本机制尚不清楚。众所周知，嘌呤能信号传导参与心血管功能的调节。在本研究中，我们检查了 P2Y(12) 受体是否可以介导 DCAN 诱导的交感神经反射。我们的结果显示，用 P2Y(12) 短发夹 RNA (shRNA) 治疗的糖尿病大鼠的血压、心率、心率变异性和交感神经放电的异常变化得到改善。同时，P2Y(12)shRNA处理的糖尿病大鼠的星状神经节(SG)中P2Y(12)受体、白细胞介素-1(IL-1)、肿瘤坏死因子-(TNF-)和连接蛋白43(Cx43)的表达降低。此外，敲除P2Y(12)受体也抑制了糖尿病大鼠SG中p38 MARK的激活。总之，这些发现表明 SG 中的 P2Y(12) 受体可能参与糖尿病自主神经病变的发生，表明 P2Y(12) 受体可能是治疗 DCAN 的潜在治疗靶点。
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 P2Y(12) 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 P2Y(12) short hairpin RNA (shRNA). Meanwhile, the expression of P2Y(12) receptor, interleukin-1 (IL-1), tumor necrosis factor- (TNF-), and connexin 43 (Cx43) in stellate ganglia (SG) was decreased in P2Y(12) shRNA-treated diabetic rats. In addition, knocking down the P2Y(12) receptor also inhibited the activation of p38 MARK in the SG of diabetic rats. Taken together, these findings demonstrated that P2Y(12) receptor in the SG may participate in developing diabetic autonomic neuropathy, suggesting that the P2Y(12) receptor could be a potential therapeutic target for the treatment of DCAN.