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Studv On Measurement Of Plasmatic Vasoactive Intestinal Peptide In Patients With Chronic Constipation And Mechanism Of Rhubarb On Aquaporin 3 In The Colon Of Constipated Rat

Posted on:2016-11-28Degree:MasterType:Thesis
Country:ChinaCandidate:Y ZhanFull Text:PDF
GTID:2284330482472903Subject:Traditional surgery
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(Part Ⅰ) Study on Postprandial Changes of Plasmatic Vasoactive Intestinal Peptide Levels in Patients with Chronic ConstipationObjectives:To investigate the postprandial changes in plasmatic levels of vasoactive intestinal peptide(VIP) in patients with chronic constipation(CC) by comparing to healthy subjects.Methods:A prospective 、 concurrent-controlled、 self-controlled and layered-controlled trial was used.Totally,22 CC patients who met the ROME Ⅲ criteria and 10 healthy adults were enrolled. Afterwards,it was measured in plasmatic concentration of VIP by enzyme-linked immunosorbent assay in all participants under different physiological conditions including fasting、 one hour after meal and three hours after meal.Results: ①There was no significant difference in the plasmatic levels of VIP between CC patients and the normal controls(P>0.05). And participants in different genders also slowed no statistic difference in the interior-group and inter-group(P>0.05). ② The plasmatic levels of VIP one hour after meal was significantly higher in female CC patients than in the male CC patients(P<0.05) and female controls(P<0.01). While male CC patients had no significant difference compared with male controls(P>0.05). ③Both male and female CC patients had lower plasmatic levels of VIP three hours after meal than the normal controls(P<0.05). ④Generally,it tended to experience a decrease within relative longer time in the plasmatic levels of VIP in female CC patients than other participants who went down initially and then rose significantly in this period.Conclusion:There may be abnormal variations in the postprandial plasmatic levels of VIP in CC patients. Which appears to be related with their pathophysiological disorders due to the important role of VIP in regulation of gastrointestinal motility and secretion. Moreover,above-mentioned correlation may be more notable in female CC patients.(Part Ⅱ) Study on Influence of Rhubarb on Expression of Aquaporin 3 in the Colon and Intestinal Motility in Loperamide-induced Constipated RatObjectives:Rhubarb is well-known for its cathartic effect,which enables rhubarb to treat chronic constipation. Recent research has been conducted on aquaporin 3(AQP3),which is considered to play an important role in the colon,particularly regarding water metabolism. Meanwhile,it provides a novel field of vision to elucidate the laxative effect of rhubarb. The aim of this study was to examine the role of AQP3 and Intestinal motility in the intervention of rhubarb for loperamide-induced constipated rats so as to explore the mechanism of laxative effect of rhubarb.Methods:Thirty Wistar rats were randomly divided into five arms,including control arm(A),model arm(B),rhubarb plus indomethacin arm(C),rhubarb plus placebo arm(D) and placebo plus indomethacin arm(E). Afterwards,it was established for constipation model by oral administration of loperamide(1.5mg·kg-1-d-1) to rats in the B,C,D and E arms during seven days. Subsequently,rats in the A and B arms were killed to validate constipation model by comparing physical condition,fecal water content and charcoal-powder propulsion rate. After that, suspension of Rhez Radix et Rhizoma(5g·kg-1) was administered orally to rats in the C and D arms,which was replaced by saline with the same dose to rats in E arm. Additionally,indomethacin(10mg·kg-1) or saline was administered intraperitoneally to rats in C,D and E arms(saline only for D arm) fifteen minutes before the lavage. Rats was autopsied after ig administration of 10% active charcoal suspension for detecting charcoal-powder propulsion rate,and the colons were removed five hours after treatment. RT-PCR,Immunohistochemistry and ELISA were used to examine the expression of AQP3 as well as concentration of PGE2 and VIP in the proximal colon.Results: ①There was significant increase in the aspect of body weight,feces in the colon and Intestinal transit time whereas fecal water content was remarkable reduced in model rats(P<0.05). ②It was observed that rhubarb could significantly accelerate Intestinal transit,raise fecal water content, decrease concentration of VIP,increase concentration of PGE2 and down-regulate the expression levels of AQP3 in constipated rats(P< 0.05). ③When pretreated with indomethacin,the purgative effects of rhubarb were markedly inhibited, namely reduced fecal water content,decreased concentration of PGE2 and up-regulated the expression levels of AQP3(P<0.05). However,it had no effect on Intestinal transit and VIP levels(P> 0.05).Conclusion:①Rhubarb may rapidly decrease AQP3 expression in the colonic epithelia via production of PGE2 to inhibit water transport from the luminal to the vascular sdie,leading to a laxative effect. ②Rhubarb may strengthen Intestinal transit function in constipated rats,which tends to be correlated with reduction of VIP and promotion of peristalsis.
Keywords/Search Tags:chronic constipation, vasoactive intestinal peptide, postprandial, pathophysiological mechanism, rhubarb, aquaporin 3, prostaglandin E2, vasoactive Intestinal peptide, loperamide-induced constipation, mechanism of laxative effect, colon
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