Effects Of Activin A On Duodenum Of Denervated Rats: Roles Of Myenteric Plexus, Interstitial Cells Of Cajal And Smooth Muscle Cells

Background:Recent researches show that the loss or damage of ENS can lead tovarious gastrointestinal motility disorders,and myenteric plexuse plays the mostimportant roles in regulation of gastrointestinal motility.BenzalkoniumChloride(BAC)is a kind of cationic disincrustant,it can damage enteric nerve tissue incertain concentration.Activin A(act A) is also called neuronal survival factor.It canprovide neuroprotective and anti-inflammatory effects,and is helpful to the repair ofinterstitial cells.But there are few reports about the neuroprotection and promotingsurvival of enteric neurons of act A,and the effects of act A on intestitial cells of cajal(ICC) and smooth muscle cells(SMCs).Objective:To explore the effect of activin A on duodenl myenteric plexus,ICC andslow waves of smooth muscle cells.Methods:All SD male rats were divided randomly into3groups:controlgroup,denervated group and Activin A treatment group.The duodenum of denervatedgroup medels were wrapped around by cotton wool soaked in0.5%BAC in0.9%salinethrough a small hole in the mesentery for30min.Then the peritoneum and treated areawere flushed with0.9%saline for3to4times.The activin A treatment group wereinjected through tail vain with activin A(0.005mg/ml)10ml/kg.d for2weeks.After2weeks neurons and ICCs in duodenal myenteric plexus were counted by immunoinhistochemistry staining.Changes of PGP9.5in duodenum were showed bywestern blot.Slow waves of smooth muscle cells were recorded with intracellularrecording.Result: The number of neurons (PGP9.5),c-kit and the quantity of PGP9.5protein ofactivin A treatment group increased significantly comparied with denervated group（P<0.01，P<0.01，P<0.01,respectively）,still reduced obviously comparied with controlgroup（P<0.01，P<0.01，P<0.01, respectively）. The amplitude of slow waves induodenal smooth muscle in the activin A treatment group were significantly higher thanthose in the denervated model group(13.8±5.39vs6.9±2.12; P <0.05),but the frequencywas not sigenificantly changed（26.5±1.28vs26.6±1.69；P>0.05）. The frequency andamplitude of slow waves in duodenal smooth muscle in the activin A treatment groupwere significantly lower than those in control (20.5±3.72vs6.9±2.12;p<0.05;26.5±1.28VS35±1.20;P<0.05).Conclution: The duodenum was denervated significantly after application of BACfor2weeks.and the ICC and slow waves of SMCs also changed.Activin A can protectenteric neurons and promote it survive.and is also helpful to the repair of ICCs andimprovement of the slow waves of SMCs. These may contriute to the treatment ofgastrointestinal disorders related to enteric neurons in the future.