The role of the sodium hydrogen exchanger‐1 in mediating diabetes‐induced changes in the retina
Notice bibliographique
Résumé
BACKGROUND: The sodium hydrogen exchanger (NHE) is a transmembrane protein responsible for alkalinization and control of intracellular acidosis by the removal of hydrogen and the subsequent influx of sodium. Our investigation attempts to determine the role of NHE-1 in the pathogenesis of early retinal microangiopathy due to diabetes. METHODS: Diabetes was induced in male Sprague-Dawley rats with a single intravenous streptozotocin injection (65 mg/kg). To examine the duration-dependent changes in NHE-1 expression, retinas from 1-, 6- and 12-week diabetic animals were analyzed. To examine the functional consequences of NHE-1 inhibition in comparison with good blood glucose control, diabetic rats were randomly assigned to poorly controlled diabetic, well-controlled diabetic, poorly controlled diabetic with cariporide groups and were compared with nondiabetic controls after six weeks. Cariporide is an orally active inhibitor of NHE-1 (6000 ppm in rat chow). At the end of the treatment period, color Doppler ultrasound was used to determine the resistivity index (RI) of the central retinal artery. The mRNA expression of endothelin (ET) isoforms 1 and 3, inducible and endothelial nitric oxide synthase (iNOS and eNOS respectively) and NHE-1 were examined. NHE-1 distribution was localized with immunohistochemistry. RESULTS: All diabetic animals showed hyperglycemia, increased glycated hemoglobin and lower body weight gain compared to nondiabetic controls. Diabetes caused an increased RI, indicative of retinal vasoconstriction, which was corrected by both cariporide treatment and good glucose control. NHE-1 was localized in the endothelium of the retinal microvasculature and the neuronal and glial components. NHE-1 mRNA expression was unchanged after 1 week and increased after 6 and 12 weeks of diabetes. Furthermore, a diabetes-induced upregulation of ET-1 and ET-3 mRNA expression after six weeks was corrected with cariporide treatment. NHE-1 inhibition of diabetic animals upregulated iNOS mRNA levels, although expression of eNOS and iNOS mRNA were not altered in poorly controlled diabetes. Improved blood glucose control with higher doses of insulin also corrected diabetes-induced increased RI by upregulating eNOS and iNOS mRNA expression. CONCLUSIONS: The results of the study suggest that NHE-1 may be involved in the regulation of several vasoactive modulators that contribute to functional alterations in diabetic retinal microangiopathy.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,004 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».