- 期刊
Effects of Various Antioxidants on Endotoxin-Induced Lung Injury and Gene Expression: mRNA Expressions of MnSOD, Interleukin-1β and iNOS
並列摘要
Antioxidants have been shown to be effective in attenuating acute lung injury. In this study, we determine the effects of various antioxidants by different mechanisms on the lipopolysaccharide (LPS)-induced changes. LPS was administered intravenously at a dose of 10 mg/kg to anesthetized rats. LPS induced a significant decrease in blood pressure (P＜0.01) and increased exhaled nitric oxide (NO) from 3.60±0.18 to 35.53±3.23 ppb (P＜0.01) during an observation period of 4 b. Plasma nitrate concentrations also increased from 0.61±0.06 to 1.54 ±0.22 μmol/l (P＜0.05). LPS-induced oxygen radical release from white blood cells isolated from rat peripheral blood also increased significantly (P＜0.001). After the experiment, the lung weight was obtained and lung tissues were taken for the determination of mRNA expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin-1β(IL-1β) and manganese superoxide dismutase (MnSOD). Histological examination of the lungs was also performed. In the control group injected with saline solution, mRNA expressions of iNOS, IL-1β, TNF-α and MnSOD were absent. Four hours after LPS administration, mRNA expressions of iNOS, IL-1, and MnSOD were significantly enhanced, but TNF-αwas not discernibly expressed. LPS also caused a twofold increase in lung weight. Pathological examination revealed endothelial cell damage and interstitial edema. Various antioxidants were given 1h after LPS administration. These agents include SOD, catalase (CAT), SOD+CAT or vitamin C (ascorbic acid). These antioxidants effectively reversed the systemic hypotension, reduced the quantity of exhaled NO and plasma nitrate concentration, and prevented acute lung injury. Administration of various antioxidants also significantly attenuated LPS. induced oxygen radical release by rat white blood cells. EPS induced mRNA expressions of MnSOD and iNOS were significantly depressed by these antioxidants. However, only SOD+CAT and vitamin C inhibited the mRNA expression of IL-1β. These results suggest that oxygen radicals are responsible for LPS-induced lung injury. Antioxidants can attenuate the lung injury by inhibiting mRNA expressions of iNOS and IL-1β.
參考文獻
延伸閱讀
- 黃國雄（2002）。Endogenous nitric oxide (NO) modulates the proliferation capacity via mitogen-activated protein kinase pathway in progenitor cells of asthmatics〔碩士論文，臺北醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0007-1704200714494928
- Li, C. L., Chen, C. C., Chiu, C. C., Lin, Y. S., Hung, R. C., Lin, C. Y., Hung, Y. C., Lin, J. W., Chi, T. Y., Lee, M. H., Lin, J. S., Tsai, W. H., Lee, M. C., & Hung, S. W. (2019). Index Evaluation of Anti-Oxidant Capacity and Anti-Aging Biological Activity of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinson's Disease in Mice. Adaptive Medicine, 11(3), 92-103. https://doi.org/10.4247/AM.2019.ABJ232
- Kuan, T. C. (2013). The effects of angiotensin peptides on angiotensin converting enzyme II regulation and matrix metalloproteinase-2 expression in cardiac cells [doctoral dissertation, National Chiao Tung University]. Airiti Library. https://doi.org/10.6842/NCTU.2013.00743
- Weng, Y. H., Kuo, C. Y., Chiu, Y. W., Kuo, M. L., & Liao, S. L. (2009). Alteration of Nitric Oxide Gas on Gene Expression of Endothelin-1 and Endothelial Nitric Oxide Synthase by a Time-and Dose-Dependent Manner in Human Endothelial Cells. The Chinese Journal of Physiology, 52(2), 1-6. https://doi.org/10.4077/CJP.2009.AMG085
- Sasaki, M., Ito, T., Kashima, M., Fukui, S., Izumiyama, N., Watanabe, A., Sano, M., Fujiwara, Y., & Miura, M. (2001). Erythromycin and clarithromycin modulation of growth factor-induced expression of heparanase mRNA on human lung cancer cells in vitro. Mediators of Inflammation, 2001(), 259-267. https://doi.org/10.1080/09629350120093731