Disertasi

Disfungsi Endotel dan Penguraian Endothelial Junction pada Luka Bakar Kritis dan Luka Bakar Non kritis. = Endothelial dysfunction: Endothelial Junction Disassembly in Critical– and Non–critical Burns.

Pendahuluan Peningkatan permeabilitas vaskular dengan manifestasi edema pada luka bakar bersifat sistemik dan menimbulkan masalah; pada luka bakar kritis kerap berakhir dengan kematian. Metode penelitian Dilakukan penelitian pada manusia, mempelajari karakteristik subyek dan pemeriksaan pembuluh darah daerah luka bakar dan non–luka bakar pada kelompok luka bakar kritis dan non–kritis. Pemeriksaan histomorfologi untuk mempelajari dan membuktikan kondisi endothelial lining, pemeriksaan imunohistokimia dan pemeriksaan ekspresi mRNA untuk mempelajari dan membuktikan disosiasi endothelial junction. Hasil Karakteristik subyek menemukan 13 variabel membedakan luka bakar kritis dan non–kritis secara bermakna; dua berperan sebagai prediktor. Pemeriksaan histomorfologi menunjukan disintegrasi endothelial lining mengindikasikan disfungsi endotel. Perubahan daerah luka bakar dan non–luka bakar baik pada kelompok luka bakar kritis maupun non–kritis tidak berbeda bermakna. Pemeriksaan imunohistokimia VE–cadherin dan occludin menunjukan disosiasi adherens – dan tight junction. Pemeriksaan yang disebutkan terakhir menunjukan disosiasi di daerah luka bakar dan non–luka bakar pada kelompok luka bakar kritis dan non–kritis tidak berbeda bermakna. Pemeriksaan Real Time–PCR menunjukan ekspresi mRNA VE–cadherin meningkat dan ekspresi mRNA occludin menurun di daerah luka bakar. Pada luka bakar kritis, ekspresi mRNA VE–cadherin dan occludin keduanya meningkat; menjelaskan peningkatan sintesis mRNA akibat disosiasi molekul VE–cadherin dan occludin. Kesimpulan Beberapa variabel karakteristik subyek (klinik dan laboratorik) menunjukan perbedaan luka bakar kritis dan non kritis, perubahan histomorfologi dan imunohistokimia menunjukan tidak ada perbedaan bermakna. Pemeriksaan mRNA menunjukan ekspresi di daerah luka bakar dan kelompok luka bakar kritis; menggambarkan peningkatan sintesis akibat adanya disosiasi kedua molekul adhesif endothelial junction.
Kata kunci: luka bakar kritis dan non–kritis, disosiasi VE–cadherin dan occludin daerah luka bakar dan non–luka bakar.



Introduction Increased of vascular permeability manifested as edema in acute burns is a systemic problem referred to devastating injury. In critical burns, it was quite often fatal. Methodology A study was set up on humans. Subject characteristics were studied to find out the difference between critical– and non–critical burns. Histomorphological investigations were carried out to find evidence on the condition of endothelial barrier. In order to find evidence of endothelial junction disassembly, the study of both immunochemistry and mRNA expression of adhesive molecules were carried out. Results Statistical analysis of subject characteristics showed 13 variables were significantly different between critical– and non–critical burns; two as predictors. Histomorphological study showed venous endothelial lining disintegration despite capillaries, indicating endothelial dysfunction. Histomorphological changes in burned area and non–burned area in critical– and non–critical burns were found not different. Studies of immunochemistry showed endothelial junction adhesion molecules dissociation in burned and non–burned area as well as in critical– and non critical burns with no significant difference. Real Time–PCR tests showed increased of VE–cadherin expression and decreased of occludin mRNA expression in burned area. Both of VE–cadherin and occludin mRNA expression were found increased in critical burns groups, showing the evidence of increased both VE–cadherin and occludin molecules synthesis following dissociation. Conclusion The study concluded that subject characteristics showed significant differences between critical– and non–critical burns. Histomorphological as well as immunochemical studies showed no difference between the two groups. However, from the point of view of molecular changes, increased of VE–cadherin mRNA expression could be observed in burned area and both VE–cadherin and occludin mRNA expression of critical burns group. This was just reflecting the increased of both of adhesive molecules synthesis following endothelial junction dissociation.
Key words: critical– and non–critical burns, dissociation of VE–cadherin and occludin in burned and non–burned area.