Abstract QS38: Effect of Compound 21, a Selective Angiotensin II Type 2 Receptor Agonist, in an Abdominal Adhesion Murine Model
Notice bibliographique
Résumé
PURPOSE: Abdominal adhesions are fibrous bands that form in response to surgical trauma, and connect visceral and/or peritoneal surfaces. Adhesions occur in over 90% of patients post-laparotomy and can lead to serious long-term complications, including infertility, small bowel obstruction and perforation, and chronic pain. This study uses a murine model of induced abdominal adhesions to study the anti-fibrotic effect of a novel selective angiotensin II type 2 receptor agonist, compound 21 (C21), in reducing abdominal adhesion formation. METHODS: The effects of C21 in vivo were assessed using a cecal abrasion model in female BALB/c mice. A laparotomy was performed and the cecum and overlying parietal peritoneum was abraded with fine grit sandpaper. Mice were divided into systemic (oral gavage) or local (intraperitoneal injection) treatment groups and were treated with C21 (10 μg/kg) or saline (vehicle control) daily for 7 days. Mice were sacrificed 8 days post-surgery and adhesions were graded by a blinded observer. Peritoneal fluid was obtained at time of sacrifice and ELISA used to quantify TGFβ levels. Laparotomy incisions were excised and CD31, CD68, and αSMA immunostaining, and picrosirius red staining were performed to assess surgical laparotomy incisional wound properties. To study the in vitro effects of C21, parietal peritoneal fibroblasts and visceral mesothelial cells were isolated and scratch wound assays performed using C21 (10 μM), angiotensin II (AngII, 1 μM), or both. RESULTS: Post-operative C21 administration, both systemically and locally, greatly reduced the formation of abdominal adhesions in vivo. Additionally, TGFβ in peritoneal fluid was reduced in mice treated with C21. Histological analysis of surgical incisions revealed no statistical difference in the number of CD31+ vessels or CD68+ cells. Expression of αSMA was reduced in C21-treated animals. Picrosirius red staining revealed no difference in collagen I and collagen III distribution in laparotomy scars between control and C21-treated animals. Laparotomy scar collagen density and surrounding dermis thickness was not significantly different between treatment groups. Cell migration of isolated parietal peritoneal fibroblasts and visceral mesothelial cells in vitro was markedly reduced in the presence of C21 compared to control or AngII. CONCLUSIONS: C21 markedly reduced or completely prevented adhesion formation both with local and systemic administration. These findings may be attributed to decreased levels of pro-fibrotic TGFβ in vivo and decreased cell migration of parietal peritoneal fibroblasts and visceral mesothelial cell migration in the presence of C21. Importantly, C21 did not appear to have histologically quantifiable effects on laparotomy wounds compared to controls. This study suggests that C21 could reduce abdominal adhesions without impeding laparotomy wound healing.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 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) | 0,001 | 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 ».