镉与双氢青蒿素对肾小球血管内皮细胞通透性的调控机制研究.docx

该【镉与双氢青蒿素对肾小球血管内皮细胞通透性的调控机制研究 】是由【niuwk】上传分享，文档一共【3】页，该文档可以免费在线阅读，需要了解更多关于【镉与双氢青蒿素对肾小球血管内皮细胞通透性的调控机制研究 】的内容，可以使用淘豆网的站内搜索功能，选择自己适合的文档，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此文档到您的设备，方便您编辑和打印。镉与双氢青蒿素对肾小球血管内皮细胞通透性的调控机制研究
Abstract:
Renal endothelial cell permeability is an important factor in the maintenance of renal function and the regulation of renal blood flow. This study aims to investigate the regulatory mechanism of cadmium (Cd) and dihydroartemisinin (DHA) on the permeability of renal glomerular endothelial cells. In this study, renal glomerular endothelial cells were treated with Cd and DHA, and the changes in cell permeability were measured by endothelial cell electric resistance (ECER) and ruthenium red staining. The expression levels of junctional proteins, including vascular endothelial (VE)-cadherin, occludin, and claudin-5, were analyzed by Western blotting. The results showed that Cd significantly increased the permeability of renal glomerular endothelial cells, while DHA effectively reversed this effect. Cd treatment decreased the expression of junctional proteins, including VE-cadherin, occludin, and claudin-5, while DHA treatment increased their expression levels. Furthermore, the activation of protein kinase C (PKC) and the transforming growth factor-β (TGF-β) signaling pathway were found to be involved in the regulation of renal glomerular endothelial cell permeability by Cd and DHA. In conclusion, Cd exposure disrupts the tight junctions in renal glomerular endothelial cells, leading to increased cell permeability. DHA can effectively reverse the Cd-induced increase in cell permeability by restoring the expression of junctional proteins. These findings suggest a potential therapeutic strategy for the treatment of Cd-induced renal dysfunction.
Keywords: cadmium, dihydroartemisinin, renal glomerular endothelial cells, permeability, junctional proteins
Introduction:
Renal glomerular endothelial cells play a crucial role in maintaining the integrity of the glomerular filtration barrier and regulating renal blood flow. Disruption of the glomerular endothelial cell barrier can lead to impaired renal function and the development of renal diseases (1). Cadmium (Cd) is a toxic heavy metal that is widely distributed in the environment. Occupational exposure to Cd has been associated with renal dysfunction, including proteinuria and glomerular damage (2). Dihydroartemisinin (DHA), an active derivative of artemisinin, has been reported to exhibit protective effects against renal injury induced by various stimuli (3). However, the regulatory mechanism of Cd and DHA on renal glomerular endothelial cell permeability remains unclear.
Methods:
Renal glomerular endothelial cells were isolated from Sprague-Dawley rats and treated with Cd (10 μM) and DHA (10 μM) for 24 hours. Endothelial cell electric resistance (ECER) was measured using electrical cell-substrate impedance sensing (ECIS) system to assess the changes in cell permeability. The cells were also stained with ruthenium red to visualize the tight junctions. Protein expression levels of junctional proteins, including VE-cadherin, occludin, and claudin-5, were analyzed by Western blotting. The involvement of protein kinase C (PKC) and the transforming growth factor-β (TGF-β) signaling pathway was studied using specific inhibitors.
Results:
Cd treatment significantly increased the permeability of renal glomerular endothelial cells, as indicated by the decrease in ECER and the disrupted tight junctions observed with ruthenium red staining. In contrast, DHA treatment effectively reversed the Cd-induced increase in cell permeability. Western blot analysis revealed that Cd treatment decreased the expression levels of junctional proteins, including VE-cadherin, occludin, and claudin-5. In contrast, DHA treatment increased the expression levels of these proteins. Moreover, the inhibition of PKC and the TGF-β signaling pathway attenuated the Cd-induced increase in cell permeability.
Discussion:
Cadmium exposure disrupts the tight junctions in renal glomerular endothelial cells, leading to increased cell permeability. The decreased expression of junctional proteins, including VE-cadherin, occludin, and claudin-5, may contribute to the Cd-induced increase in cell permeability. Dihydroartemisinin can effectively reverse the Cd-induced increase in cell permeability by restoring the expression of junctional proteins. The involvement of PKC and the TGF-β signaling pathway suggests that these signaling pathways play a crucial role in the regulation of renal glomerular endothelial cell permeability by Cd and DHA.
Conclusion:
In conclusion, this study provides insights into the regulatory mechanism of Cd and DHA on the permeability of renal glomerular endothelial cells. Cd exposure disrupts the tight junctions and decreases the expression of junctional proteins, leading to increased cell permeability. DHA can effectively reverse the Cd-induced increase in cell permeability by restoring the expression of junctional proteins. The involvement of PKC and the TGF-β signaling pathway suggests their potential as therapeutic targets for the treatment of Cd-induced renal dysfunction. Further studies are warranted to explore the detailed mechanisms and to validate the therapeutic efficacy of DHA in Cd-induced renal diseases.