Aller María-Ángeles, Martínez Vicente, Arias Ana, Nava Maria-Paz, Cuervas-Mons Valentín, Vergara Patri, Arias Jaime
Department of Surgery, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
Department of Cell Biology, Physiology and Immunology, Veterinary School, Autonoma University of Barcelona, 08193 Cerdanyola del Vallès, Spain.
Clin Res Hepatol Gastroenterol. 2019 Oct;43(5):561-574. doi: 10.1016/j.clinre.2019.02.001. Epub 2019 Mar 8.
Splanchnic mast cells increase in chronic liver and in acute-on-chronic liver diseases. We administered Ketotifen, a mast cell stabilizer, and measured the mast cells in the splanchnic organs of cholestatic rats.
These groups were studied: sham-operated rats (S; n = 15), untreated microsurgical cholestasic rats (C; n = 20) and rats treated with Ketotifen: early (SK-e; n = 20 and CKe; n = 18), and late (SK-l; n = 15 and CK-l; n = 14).
The cholestatic rats showed systemic and splanchnic impairments, such as ascites, portal hypertension, and biliary proliferation and fibrosis. The rats also showed a splanchnic increase of TNF-α, IL-1β and MCP-1, and a reduction of IL-4, IL-10 and antioxidants. An increase of VEGF in the ileum and mesenteric lymphatic complex was associated with a liver reduction of TGF-β1. Ketotifen reduces the degree of hepatic insufficiency and the splanchnic inflammatory mediators, as well as VEGF and TGF-ß1 levels. Ketotifen also reduces the connective tissue mast cells in the mesenteric lymphatic complex of cholestatic rats, while increases the hepatic mucosal mast cells.
In cholestatic rats, Ketotifen improves liver function and ascites, and also reduces pro-inflammatory mediators in the splanchnic area. The decrease in connective tissue mast cells in the mesenteric lymphatic complex due to the administration of Ketotifen would lead to the improvement of the inflammatory splanchnic response, and consequently the abovementioned complications.
在内脏中，肥大细胞在慢性肝病和慢加急性肝病中数量会增加。我们给予肥大细胞稳定剂酮替芬，并测量胆汁淤积大鼠内脏器官中的肥大细胞。
研究了以下几组：假手术大鼠（S组；n = 15）、未经治疗的显微外科胆汁淤积大鼠（C组；n = 20）以及用酮替芬治疗的大鼠：早期治疗组（SK-e组；n = 20和CKe组；n = 18），以及晚期治疗组（SK-l组；n = 15和CK-l组；n = 14）。
胆汁淤积大鼠表现出全身和内脏功能损害，如腹水、门静脉高压以及胆管增生和纤维化。大鼠还表现出内脏中肿瘤坏死因子-α、白细胞介素-1β和单核细胞趋化蛋白-1增加，以及白细胞介素-4、白细胞介素-10和抗氧化剂减少。回肠和肠系膜淋巴复合体中血管内皮生长因子的增加与肝脏中转化生长因子-β1的减少相关。酮替芬可降低肝功能不全的程度以及内脏炎症介质，以及血管内皮生长因子和转化生长因子-β1的水平。酮替芬还可减少胆汁淤积大鼠肠系膜淋巴复合体中的结缔组织肥大细胞，同时增加肝脏黏膜肥大细胞。
在胆汁淤积大鼠中，酮替芬可改善肝功能和腹水，还可减少内脏区域的促炎介质。由于给予酮替芬导致肠系膜淋巴复合体中结缔组织肥大细胞减少，这将导致内脏炎症反应得到改善，从而改善上述并发症。
