Department of Medicine, Medical College of Jiaying University, Meizhou, China; Cardiovascular Research Center, Shantou University Medical College, Shantou, China.
Cardiovascular Research Center, Shantou University Medical College, Shantou, China.
Eur J Pharmacol. 2020 Sep 5;882:173254. doi: 10.1016/j.ejphar.2020.173254. Epub 2020 Jun 15.
Diabetic nephropathy (DN), one of the main causes of end-stage renal disease, still remains as a challenge of clinical management. This study aimed to determine whether deficiency of the thromboxane (TX) prostanoid receptor (TP), which mediates the contractile activities of all prostanoids, alleviates the development of DN and if so, to examine the underlying mechanism(s). Diabetes was induced by high fat diet and streptozotocin injection in wild-type (WT) mice and those with TP deficiency (TP). Here we show that WT and TP mice developed diabetes with a similar blood glucose level; however, signs of renal functional impairments and pathologies occurred to a lesser extent in TP than in WT mice. Also, the extent of an increase in the expression level of transforming growth factor-β1 (TGF-β1), a common pathological mediator of DN, in diabetic renal cortexes of TP mice was lower than that of WT counterparts. Moreover, we noted that expression levels of cyclooxygenase (COX)-2 and calcium-dependent phospholipase A (cPLA) as well as levels of prostaglandin E and TXA in diabetic renal cortexes were increased as compared to those of non-diabetic conditions. These results thus demonstrate that possibly due to up-regulated cPLA and COX-2 that lead to increased prostanoid syntheses in diabetic renal cortexes, TP alleviates DN development. In addition, our results suggest that such an effect of TP might be related to the suppression of TGF-β1 up-regulation that is commonly associated with the disease condition.
糖尿病肾病（DN）是终末期肾病的主要病因之一，仍然是临床管理的挑战。本研究旨在确定是否缺乏血栓素（TX）前列腺素受体（TP），该受体介导所有前列腺素的收缩活性，可以减轻 DN 的发展，如果是这样，则检查潜在的机制。在野生型（WT）小鼠和 TP 缺乏（TP）小鼠中，通过高脂肪饮食和链脲佐菌素注射诱导糖尿病。在这里，我们发现 WT 和 TP 小鼠的血糖水平相似，糖尿病发生；然而，与 WT 小鼠相比，TP 小鼠的肾功能损害和病理迹象的发生程度较小。此外，在 TP 小鼠的糖尿病肾脏皮质中，转化生长因子-β1（TGF-β1）的表达水平增加的程度低于 WT 小鼠。此外，我们注意到，与非糖尿病状态相比，在糖尿病肾脏皮质中，环氧化酶（COX）-2 和钙依赖性磷脂酶 A（cPLA）的表达水平以及前列腺素 E 和 TXA 的水平均升高。因此，这些结果表明，可能由于 cPLA 和 COX-2 的上调导致糖尿病肾脏皮质中前列腺素合成增加，TP 减轻了 DN 的发展。此外，我们的结果表明，TP 的这种作用可能与 TGF-β1 上调的抑制有关，该上调通常与疾病状况有关。
