Chen Yuelin, Shen Yuechun, Nie Ya, Chen Zhongxin, Wang Huang, Liao Huang, Li Jun
Department of Cardiology, Affiliated Zhongshan Hospital of Guangdong Medical University, Zhongshan, Guangdong 528415, P.R. China.
Department of Cardiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China.
Exp Ther Med. 2017 Nov;14(5):5097-5102. doi: 10.3892/etm.2017.5177. Epub 2017 Sep 21.
The adipocyte-derived hormone leptin is associated with hypertension. The involvement of cyclooxygenase-2 (COX-2) and its downstream vasomotor products prostaglandin (PG) and thromboxane (TX)A in the mechanisms of action of leptin have remained elusive. The aim of the present study was to investigate the effects of leptin on the expression of COX-2 by rat aortic endothelial cells (RAECs) and the concentration of its products, represented by 6-keto PGF and TXB, in the culture media. RAECs were isolated, cultured and identified by immunofluorescence staining. The RAECs were incubated with different concentrations of leptin (10, 10 and 10 M) for various durations (36 or 48 h). COX-2 mRNA and protein expression in the cells was detected by reverse-transcription quantitative PCR and western blot analysis, respectively. The vasodilator 6-keto PGF and the vasoconstrictor TXB were detected in the supernatant by ELISA. The cultured cells displayed specific factor VIII expression in the cytoplasm. Compared with the PBS-treated control group, leptin significantly increased the expression of COX-2 mRNA and protein in a time- and dose-dependent manner (P<0.01). Furthermore, the vasodilator 6-keto PGF was increased and the TXB/6-keto PGF ratio decreased only with relatively high concentrations of leptin (10 or 10 M; P<0.01), but TXB levels were not affected (P>0.05). In conclusion, leptin significantly increased the expression of inflammatory marker COX-2 and its downstream product 6-keto PGF, while also decreasing the TXB/6-keto PGF ratio . These observations suggested that COX-2 may have an important role in the effects of leptin on inflammation, such as the low-inflammatory disease hypertension. However, selective COX-2 inhibitors may increase the risk of hypertension due to inhibiting 6-keto PGF, the vasodilator product of COX-2.
脂肪细胞衍生的激素瘦素与高血压有关。环氧化酶-2（COX-2）及其下游血管舒缩产物前列腺素（PG）和血栓素（TX）A在瘦素作用机制中的参与情况仍不清楚。本研究的目的是探讨瘦素对大鼠主动脉内皮细胞（RAECs）中COX-2表达及其在培养基中以6-酮-前列腺素F和血栓素B表示的产物浓度的影响。通过免疫荧光染色分离、培养和鉴定RAECs。将RAECs与不同浓度的瘦素（10、10和10μM）孵育不同时间（36或48小时）。分别通过逆转录定量PCR和蛋白质印迹分析检测细胞中COX-2 mRNA和蛋白质表达。通过酶联免疫吸附测定法检测上清液中的血管舒张剂6-酮-前列腺素F和血管收缩剂血栓素B。培养的细胞在细胞质中显示出特异性因子VIII表达。与磷酸盐缓冲液处理的对照组相比，瘦素以时间和剂量依赖性方式显著增加COX-2 mRNA和蛋白质的表达（P<0.01）。此外，仅在相对高浓度的瘦素（10或10μM；P<0.01）作用下，血管舒张剂6-酮-前列腺素F增加，血栓素B/6-酮-前列腺素F比值降低，但血栓素B水平未受影响（P>0.05）。总之，瘦素显著增加炎症标志物COX-2及其下游产物6-酮-前列腺素F的表达，同时也降低血栓素B/6-酮-前列腺素F比值。这些观察结果表明，COX-2可能在瘦素对炎症（如低炎症性疾病高血压）的影响中起重要作用。然而，选择性COX-2抑制剂可能由于抑制COX-2的血管舒张剂产物6-酮-前列腺素F而增加高血压风险。
