Effect Of IL-1β On The Spontaneous Contraction Of Isolated Rats’Pyloric Sphincter

BackgroundPyloric sphincter can control both of the residence time of food in stomach and the discharging speed into the duodenum to prevent excessive gastric emptying and duodenogastric reflux. This function is because of the resting pressure coming from continuing tension and the pressure coming from cyclical contraction.The contraction of pyloric sphincter is regulated by the concentration of intracellular Ca2+, which is mediated by the calcium channels, calcium pump, uptake and release of calcium in sarcoplasmic reticulum and Na+-Ca2+exchanger.It was reported that IL-1β inhibited the contraction of rat vascular smooth muscle by NO signaling pathways, enhanced the amplitude of rabbit uterine smooth muscle contraction through PGE pathway. In addition, IL-1β inhibited the contraction induced by phenylephrine on rat aorta via activating ATP-sensitive K+channels. It hasn’t reported if IL-1β can inhibit the spontaneous contraction of the pyloric sphincter.ObjectiveThis study was planned to investigate the effect and mechanism of IL-1β on the spontaneous contractions of isolated rats’pyloric sphincter in order to replenish the pharmacological effect of IL-1β, then provided laboratory basis for its clinical application.MethodsMale or female Sprague-Dawley rats were divided into seven groups randomly: normal group, IL-1β group, calcium-free group, indomethacin group, glibenclamide group, methylene blue trihydrate group and L-NAME group, then killed by cervical dislocation to excise the pyloric sphincter. Perfusion of isolated rat pyloric sphincter was used to evaluate the effect of each group. All data were analyzed using SPSS17.0statistical software.Resultsl.IL-1β group:Addition of the IL-1β (2ng/ml,20ng/ml,200ng/ml) induced an inhibition of the spontaneous contractions. The amplitude, frequency and tension were decreased (P <0.05, n=9).2. Intervention IL-1β group:a. Compared with the normal krebs solution group, the inhibition of IL-1β was insignificantly on the spontaneous contractions of pyloric sphincter in calcium-free solution (P>0.05, n=6).b. Pretreatment of the tissues with glyburide (5μM) was without significant effects on the spontaneous contractions responses to IL-1β (P>0.05, n=6).c. Pretreatment of the tissues with indomethacin (l0μM) attenuated the inhibitory effects of IL-1β. The amplitude, frequency and tension were increased compared with indomethacin absented (P<0.05, n=6).d. Pretreatment of the tissues with methylene blue trihydrate (10μM) markedly attenuated the inhibitory effects of IL-1β. The amplitude, frequency and tension were increased compared with methylene blue trihydrate absented (P<0.01, n=6).e. Pretreatment of the tissues with L-NAME (100μM) markedly attenuated the inhibitory effects of IL-1β. The amplitude, frequency and tension were increased compared with L-NAME absented (P<0.01, n=6).ConclusionIL-1β can inhibit spontaneous contractions on rats’ isolated pyloric sphincter. The inhibitory effects of IL-1β can be attenuated by methylene blue trihydrate, L-NAME and indomethacin. It indicates that has a certain relationship with the levels of NO, cGMP and cAMP in intracellular.