Anti-Inflammatory Effects of Lactoferrin on Hyperoxia-Induced Systemic Inflammatory Responses using NF-κB/luciferase Transgenic Mice
| Autor: | Wen-Hui Chang, 張雯惠 |
|---|---|
| Rok vydání: | 2013 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 101 Hyperoxia is used to cure hypoxemia in clinical symptoms, through oxygen supplementation to maintain adequate tissue and respiratory oxygenation. However, exposure to hyperoxia may produce reactive oxygen species (ROS) in vivo easily. Lactoferrin (LF) is an iron-binding glycoprotein found in mammal’s milk, and it can improve immunomodulatory effects. Additionally, many studies demonstrated that LF has a number of biological functions including anti-inflammatory, anti-oxidant, anti-viral effects, and so on. Since patients were treated with hyperoxia for a long term, ROS would exacerbate disease with toxic metabolites. Therefore, we investigated the anti-inflammatory effects of LF on hyperoxia-induced systemic inflammatory responses. The anti-inflammatory therapy model was using NF-κB/luciferase transgenic mice (Tg mice), which are carrying the luciferase gene under the control of NF-κB. When NF-κB was activated by hyperoxia, luciferase protein would show higher expression. Luciferase protein would response with liciferin from injection, and then used non-invasive in vivo imaging system (IVIS) to observe luminescence excitation performance immediately. The transgenic mice with homozygous NF-κB/luciferase (NF-κB-Luc+/+) genotype were randomly assigned to four groups for treatments (n ≥ 5): (1) NF-κB-Luc+/+ mice treated with water, (2) NF-κB-Luc+/+ mice treated with water and hyperoxia for 72 hours, (3) NF-κB-Luc+/+ mice treated with 150 mg/kg LF and hyperoxia for 72 hours, and (4) NF-κB-Luc+/+ mice treated with 300 mg/kg LF and hyperoxia for 72 hours. And NF-κB-Luc+/+ mice pre-treated LF or water daily for 14 days. We found that the highest expression of luciferase protein in hyperoxia-induced NF-κB-Luc+/+ Tg mice were detected in the kidney tissue, and also weaker expression in lung tissue by IVIS, indicating that we established the in vivo image model successfully. As Tg mice were treated with LF, the lower expression of luciferase were observed in lung and kidney, and the ROS and p-MAPK expression also decreased significantly（p < 0.01）under hyperoxia condition. The decayed ratio of IκB also was decreased significantly. Additionally, LF effectively decreased the expression of the inflammatory factors including IL-6, IL-1β, and TNF-α（p < 0.01）. Data suggested that LF decreased the activation of NF-κB and exerted an anti-inflammatory effect under the hyperoxia-induced injury. We speculated that LF could be absorbed through specific LF receptors of intestinal mucosal cells. And LF would be transported to lung and kidney to decrease the produce of ROS in intracellular or blood flow. Besides, LF with Iron ions could balance the ROS activities, decrease the injury from radicals and inhibit the inflammatory effect. In the following study, we will continue to investigate and track the inflammation pathway. Furthermore, using the characteristics of kidney with highly luciferase expression, test the inflammatory and suppress effect in the local tissue. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|