Cao Yanan, He Zhenghua, Zhu Maoen, Gao Xiaowei, Yang Yue, Zhang Junjie, Pan Yundan, Guo Qulian, Peng Yonggang, Wang E
1 Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
2 Department of Anesthesiology, Shands Hospital, University of Florida, Gainesville, FL, USA.
Pulm Circ. 2018 Oct-Dec;8(4):2045894018800702. doi: 10.1177/2045894018800702. Epub 2018 Aug 30.
Pulmonary fibrosis is often concomitant with myocardial injury. We studied sevoflurane's effects on cardiac function and the expression of the TLR4/inducible nitric oxide synthase (iNOS) signaling pathway on a pulmonary fibrosis model. C57BL/6J wild-type (WT) and TLR4-deficient (TLR4) mice were randomly divided into a control group and a pulmonary fibrosis group. The model of pulmonary fibrosis was induced by treatment with paraquat (PQ; 20 mg/kg). Four weeks after PQ administration, mice were tested for body weight changes, and histopathology and hydroxyproline in lung. Left ventricular function in each group of mice was measured by echocardiogram before and after sevoflurane inhalation. The expression of TLR4 and iNOS protein were analyzed. Pulmonary fibrosis mice were fed lenalidomide (50 mg/kg/day) for three days and cardiac function was assessed before and after sevoflurane inhalation. WT pulmonary fibrosis mice showed pathological damage and excessive deposition of collagen in the lung and heart. Left ventricular function decreased after four weeks of PQ exposure. TLR4 mice were resistant to pulmonary fibrosis like pathological damage and the effect of sevoflurane on heart rate and ejection fraction than that of WT mice. TLR4 and iNOS expression in WT pulmonary fibrosis mice increased significantly after sevoflurane inhalation. Lenalidomide treatment alleviated the effect of sevoflurane on heart rate and ejection fraction in WT pulmonary fibrosis mice. Sevoflurane inhibits cardiac function in pulmonary fibrosis mice through the TLR4/iNOS pathway. Lenalidomide attenuated the sevoflurane's effect on the cardiac function of mice with pulmonary fibrosis.
肺纤维化常伴有心肌损伤。我们在肺纤维化模型上研究了七氟醚对心脏功能以及Toll样受体4/诱导型一氧化氮合酶（iNOS）信号通路表达的影响。将C57BL/6J野生型（WT）和Toll样受体4缺陷型（TLR4）小鼠随机分为对照组和肺纤维化组。通过百草枯（PQ；20mg/kg）处理诱导肺纤维化模型。给予PQ四周后，检测小鼠体重变化、肺组织病理学及羟脯氨酸含量。每组小鼠在吸入七氟醚前后通过超声心动图测量左心室功能。分析Toll样受体4和iNOS蛋白的表达。肺纤维化小鼠给予来那度胺（50mg/kg/天）三天，并在吸入七氟醚前后评估心脏功能。WT肺纤维化小鼠表现出肺和心脏的病理损伤及胶原过度沉积。PQ暴露四周后左心室功能下降。TLR4小鼠对肺纤维化样病理损伤具有抗性，且七氟醚对其心率和射血分数的影响小于WT小鼠。WT肺纤维化小鼠吸入七氟醚后Toll样受体4和iNOS表达显著增加。来那度胺治疗减轻了七氟醚对WT肺纤维化小鼠心率和射血分数的影响。七氟醚通过Toll样受体4/iNOS途径抑制肺纤维化小鼠的心脏功能。来那度胺减弱了七氟醚对肺纤维化小鼠心脏功能的影响。
