Department of Respiratory Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People's Republic of China.
Physiol Res. 2019 Jun 30;68(3):445-455. doi: 10.33549/physiolres.934010.
Obstructive sleep apnea (OSA) has been demonstrated to be implicated in disorder of insulin secretion and diabetes mellitus. In this study, we aimed to evaluate the protective role of tempol, a powerful antioxidant, in chronic intermittent hypoxia (IH)-induced pancreatic injury. The rat model of OSA was established by IH exposure. The pathological changes, increased blood-glucose level, and raised proinsulin/insulin ratio in pancreatic tissues of rats received IH were effectively relieved by tempol delivery. In addition, the enhanced levels of pro-inflammatory cytokines, TNF-alpha, IL-1beta, IL-6, and inflammatory mediators, PGE2, cyclooxygenase-2 (COX-2), NO, and inducible nitric oxide synthase (iNOS) in pancreatic tissue were suppressed by tempol. Moreover, tempol inhibited IH-induced apoptosis in pancreatic tissue as evidenced by upregulated Bcl-2 level, and downregulated Bax and cleaved caspase-3 levels. Finally, the abnormal activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) signaling pathways induced by IH was restrained by tempol administration. In summary, our study demonstrates that tempol relieves IH-induced pancreatic injury by inhibiting inflammatory response and apoptosis, which provides theoretical basis for tempol as an effective treatment for OSA-induced pancreatic injury.
阻塞性睡眠呼吸暂停（OSA）已被证明与胰岛素分泌紊乱和糖尿病有关。在这项研究中，我们旨在评估一种强大的抗氧化剂——tempol 在慢性间歇性低氧（IH）诱导的胰腺损伤中的保护作用。通过 IH 暴露建立 OSA 大鼠模型。Tempol 给药有效缓解了大鼠 IH 后胰腺组织的病理变化、血糖水平升高和胰岛素原/胰岛素比值升高。此外，Tempol 还抑制了胰腺组织中促炎细胞因子 TNF-α、IL-1β、IL-6 和炎症介质 PGE2、环氧化酶-2（COX-2）、NO 和诱导型一氧化氮合酶（iNOS）的水平升高。此外，Tempol 通过上调 Bcl-2 水平和下调 Bax 和 cleaved caspase-3 水平抑制 IH 诱导的胰腺组织凋亡。最后，Tempol 抑制了 IH 诱导的丝裂原活化蛋白激酶（MAPK）和核因子 kappa-轻链增强子的活化 B 细胞（NF-κB）信号通路的异常激活。综上所述，我们的研究表明，Tempol 通过抑制炎症反应和细胞凋亡缓解 IH 诱导的胰腺损伤，为 Tempol 作为治疗 OSA 诱导的胰腺损伤的有效方法提供了理论依据。
