Role and Mechanism of Visfatin in Dysfunction of Colonic Smooth Muscle Contraction in Rats / 胃肠病学

ABSTRACT

Background: Obesity is associated with many functional gastrointestinal disorders, such as gastrointestinal motility disorder. Previous studies showed that adipose tissue-derived adipokine visfatin (VF), which increased in obesity, might impair myometrial contractility and cause vascular smooth muscle relaxation. Aims: To investigate the effect of VF on contractility of colonic smooth muscle in rats and its underlying mechanism. Methods: Segments of distal colon from normal Sprague-Dawley (SD) rats were dissected into strips (0.3 cm × 0.8 cm), and the effect of VF on contractility of muscle strips was measured by biological signal collection system. In in vitro study, colonic smooth muscle cells (SMCs) from neonatal SD rats were cultured and treated with VF; phosphorylation of myoglobulin light chain (MLC) and expression of calcium channel protein Cav1.2 (α1 subunit) were assessed by Western blotting. Cultured in buffer solution with or without calcium, the acetylcholine-stimulated intracellular Ca2+ level in SMCs was detected by confocal laser scanning microscopy. Results: In muscle strip contractility assay, VF (200 ng/mL) significantly inhibited the contractility of colonic smooth muscle strip from normal adult rats (P<0.05). In cultured colonic SMCs, VF (200 ng/mL) down-regulated the calcium channel protein Cav1.2 expression and reduced the intracellular Ca2+ level and MLC phosphorylation (P<0.05). Conclusions: VF may down-regulate the expression of calcium channel protein Cav1.2 on the membrane of colonic SMCs and cause colonic dysmotility by interfering with Ca2+ signaling and smooth muscle contractility.