| ObjectiveIrritable bowel syndrome(IBS) is one of the most common gastrointestinal disorders and can dramatically affect the quality of a sufferer's life. However, up to now its pathogenesis is still unclear. At present, the majority of researchers think that multiple factors are involved in the pathogenesis of IBS, such as intestinal motility dysfunction, visceral hpersensitivity, mucosa microscopic inflammation, infection, neuro endocrine abnormality, heredity factor, diet intolerance, and so on. Motility dysfunction and visceral hpersensitivity are considered to be the pathophysiology basis of IBS. Protease-activated receptors(PARs) belong to the family of seven transmembrane domain G protein-coupled receptors and include four isoforms. It has been shown that PARs is widely distributed in the gastrointestinal tract where it is involved in multiple pathological responses to modify motility, sensation and inflammation of gastrointestinal tract. In recent years, more and more researchers pay close attention to its roles in the process of functional gastrointestinal disorders. However, the animal model was usually applied in current experiments, as well as the research on PARs is rare in human. Therefore, our aim was to examine the difference of the PARs expressions in the colon mucosal tissue of the patients with IBS and to investigate the functions of PARs in the process of IBS.Materials and MethodsThe subjects were selected from outpatient and inpatient services of changhai hospital in Shanghai. (1) normal controls:18 subjects without condition were selected as control group, with the average age was 53.11±13.65. Among them,14 cases were male and 4 were female. All have not any gastrointestinal disease history and clinical symptoms. (2) diarrhea-predominant irritable bowel syndrome (D-IBS) group:28 patients of D-IBS was diagnosed according to the Rome III criteria, with the average age was 49.04±13.73, of them 15 were male and 13 were female. (3) constipation-predominant irritable bowel syndrome (C-IBS) group:12 patients of D-IBS was diagnosed according to the Rome III criteria, with the average age was 51.08±10.11, of them 5 were male and 7 were female. There is no significant difference between the age and sex. Routine examinations and colonoscopy were performed for all subjects without positive physical signs to exclude organic diseases. All patients had macroscopically normal bowel mucosa on examination. Mucosal biopsy specimens were taken using standard biopsy forceps from all subjects from the rectosigmoid junction in order to standardise the site of sampling. The biopsies were used for western blotting and real-time PCR to observe the expressions of PARs.ResultsAnalyzed by western blotting approach, the protein expressions of PAR2 and PAR4 in patients with D-IBS were significantly higher than those in the normal controls (0.99±0.67 vs 0.63±0.38, P=0.038 and 0.37±0.14 vs 0.25±0.11, P=0.013); furthermore, The results of real-time PCR were in accordance with those of western blotting(5.71±2.54 vs 4.15±1.87, P=0.040 and 5.51±2.27 vs 3.77±2.06, P=0.031). However, the results of two methods all showed that the expressions of PAR1 in bowel mucosa did not differ significantly between two groups. Furthermore, the differences of the expressions of PAR2 protein and PAR4 mRNA between D-IBS group and C-IBS group have no sense in statistics (0.08±0.07 vs 0.07±0.06, P=0.908 and 3.28±0.95 vs 2.14±0.62, P=0.204).ConclusionThe expressions of PARs, especially PAR2 and PAR4, were increased in the colon mucosa of IBS patients, which suggests that the activation of the two PARs receptor may play some roles in the process of IBS and are associated with some symptoms, such as abdominal pain and distension. Therefore, PARs might be a new therapeutic targets of IBS.
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