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The Mechanism Research Of HCN2 On Regulating Gastrointestinal Motility

Posted on:2011-10-24Degree:MasterType:Thesis
Country:ChinaCandidate:H YanFull Text:PDF
GTID:2154360308459722Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
The modulation of Gastrointestinal tract is dominated not only by autonomic nerve, but also regulated by independent enteric nervous system (ENS). However, ENS of specific regulating mechanisms of the gastrointestinal tract to be remained. So the further interpretation about the mechanism of ENS -regulated gastric motility is very important to the clinical treatment of gastrointestinal disorders. The rhythmic electric activity of the gastrointestinal tract smooth muscle (slow wave activity) is the basis of the pacing of motivation of gastrointestinal tract. The locomotion of gastrointestinal tract involves extremely complicated processes, the capital part is the contraction of Smooth muscle cell (SMC) which is originated from the variation of electric activity of the cytomembrane which is influenced by multiple factors. Hyperpolarization activated cyclic nucleotide gated (HCN) channels family is the Molecular basis of funny current (If), it comes from a non-selective voltage-gated cation channel family. HCN has been identified as an important channel in the regulation of slow wave rhythm. The present study on HCN is still limited to the regulation of brainstem respiratory center on the respiratory rhythm and sino-atrial node (SAN) on cardiac rhythm. While the modulation of HCN on the motor function of gastrointestinal tract has not been reported yet. This experiment observed the distributions of hyperpolarization-activated, cyclicnucleotide gated type 2 in gastrointestinal tract and detectived the relationship of its Co-localization with some neurotransmitters by using the fluorescence double-labeling stain method. Based on this, observed the changes of The frequency and amplitude of vibration of contraction of jejunnm muscle strip when HNC2 receptor agonist or antagonis was treated. Through this research, it can establish the role and status of HCN2 in regulation of the mechanism of gastrointestinal motility, for providing theoretical basis on the regulation of gastrointestinal motility.Methods:â‘ The fluorescence double-labeling stain to double-label PGP9.5 and HCN2, and to double-labeling HCN2 separately with SP CGRP and VIP.â‘¡Set up the isolated jejunnm muscle strip model of rats, observed the changes of frequency andamplitude of wave in isolated jejunnm muscle strip of rats before and after adding agonist CAMP of HCN2 receptor or inhibitor MDL of HCN2 receptor.â‘¢Check the change of the contents of SP and VIP in the perfusate by euzymelinked immunosorbent assay before and after adding agonist CAMP and inhibitor MDL of HCN2 channels to the isolated jejunnm muscle strip model of rats separately.Results:1. HCN2 is based on the distribution of bead-like structure in the gastrointestinal nerve terminals. HCN2, which separately with SP CGRP and VIP have been double-labeled in gastrointestinal tract.2. Under normal condition, muscle strip was able to contract steadily after incubating for 1 hour. The frequency and amplitude of vibration of contraction of jejunnm muscle strip altered significantly when HNC2 receptor agonist, CAMP or HCN2 antagonis MDL was treated.3. After adding the agonist CAMP of HCN2 receptor, the content level of SP increases significantly both in toroid muscle and longitudinal muscle (P<0.05), while the content level of VIP decreases significantly (P<0.05). After adding inhibitor MDL of HCN2 receptor, the content of SP decreases significantly both in toroid muscle and longitudinal muscle (P<0.05), while the content of VIP increases significantly (P<0.05).Conclusions:HCN2 Existis in the gastrointestinal tract and coexists with neurotransmitters. The alteration of the function of HCN2 receptor can influence contractile motility of the isolated jejunnm muscle strip in rats, and it influences the content of SP in the perfusate positively, while for the VIP negatively, which conforms with the modulation of SP and VIP on Gastrointestinal tract,so it is suggested that HCN2 maybe plays a key role on regulating the gastrointestinal motilities.
Keywords/Search Tags:HCN2, VIP, SP, CGRP, gastrointestinal motility
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