| Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder that is characterized by chronic abdominal pain and changes in bowel habits. It was reported that global prevalence is approximately 5-30%, accounting for 34.3% of the total number of outpatient gastroenterology in our country, and patients with diarrhea-predominant irritable bowel syndrome (D-IBS) comprise a substantial proportion of the overall IBS population. D-IBS belongs to the category of diarrhea, pain and other areas in traditional chinese medicine, liver depression and spleen deficiency is the basic pathogenesis of D-IBS in traditional chinese medicine. The complexity of D-IBS pathogenesis makes it difficult to cure with persistent or recurrent symptoms, patients often seek medical treatment, which seriously affect their physical and mental health as well as the quality of life. It has been reported that prediabetes is more frequently found in the IBS group than in the control group. It is still not clear the mechanism of the incidence of diabetes in patients with D-IBS, the TCM Syndrome and their Psychological health, quality of life.miRNAs are small, endogenous, and approximately 21-23 nucleotide long non-coding RNAs. By binding through partial or inparial sequence complementarity to the 3’-UTR of target mRNAs, which are known to regulate target gene expression post-transcriptionally by repressing translation or decreasing mRNA. There are few investigation on aberrant miRNA expression in the development of IBS and no report on the miRNA profile of D-IBS complicated type 2 diabetes mellitus(T2DM). It is not fully understood the biological function of differentially expressed miRNAs in D-IBS complicated T2DM.In the present study, we first investigated the incidence of diabetes in D-IBS by using demographic checklists, symptoms questionnaire and Chinese version IBS-QOL. Microarray technology were used to examine the miRNA expression profiles of D-IBS complicated T2DM compared with T2DM, D-IBS and control subjects. GO and KEGG analyses were applied to determine the roles of these target genes. Further more, we established and evaluated the rat model of D-IBS complicated T2DM with liver depression and spleen deficiency. Finally, we studied miR-29b biological function this rat model of D-IBS complicated T2DM with liver depression and spleen deficiency. The research project was divided into four parts as followings:Part I Syndrome in TCM and quality of life on patients with D-IBS complicated T2DMObjective:To compare the occurrence of diabetes IBS cases and matched controls; to investigate demographic characteristics, TCM syndrome, psychological status and quality of life on patients with D-IBS complicated T2DM.Methods:From May 2013 to May 2015, there are 388 consecutive Roma III criteria-positivc D-IBS patients from the first affiliated hospital of medical college of Yangzhou University, and there are 220 healthy individuals in the control group who were matched to cases based on age, sex and body mass index (BMI). We excluded all cases and controls with T2DM that were based on the results of the oral glucose tolerance test. The study was approved by the Ethics Committee of Affiliated Hospital to Yangzhou University (Jiangsu, China), and the written informed consent was obtained from each subject. Evaluation are performed by using demographic characteristics, TCM syndrome, psychological status and quality of life on patients with D-IBS complicated T2DM.Results:Diabetes was more frequent in the IBS group than in the control group, and D-IBS complicated T2DM is related to the course of disease. There is a higher risk of diabetes as patients with the longer duration about D-IBS. The predominant TCM syndrome in D-IBS complicated T2DM was liver depression and spleen deficiency syndrome accounting for 74.4%. There are more severe clinical gastrointestinal symptoms and more severe presence of anxiety and depression for the patients with D-IBS complicated T2DM. Also these patients experience momentous impairment in quality of life.Conclusion:Thus, given the higher diabetes occurrence in patients with D-IBS, D-IBS may indirectly cause a higher risk of diabetes. Predominant TCM syndrome was liver depression and spleen deficiency syndrome in D-IBS complicated T2DM, these patients had worse gastrointestinal symptoms, mental status and the life quality.Part II Research on circulating microRNA profile in D-IBS complicated T2DMObjective:To investigate on circulating microRNA profile and identify the differentially expressed miRNAs in D-IBS complicated T2DM. Bioinformatics analyses were applied to determine the roles of these target genes.Methods:Three samples were selected randomly from each group for microRNA microarray analysis. Microarray technology was taken to examine the miRNA expression profiles of D-IBS complicated T2DM, the target genes of differentially expressed miRNAs were predicted by three databases (Targetscan, microRNAorg and pita). GO and KEGG analyses were applied to determine the biology process, cellular component, molecular function and signaling pathway of these target genes. Among the screening results, miR-106b、miR-29b\miR-26a were selected for further validation in D-IBS complicated T2DM by qRT-PCR, and ROC analysis were performed for relative expression of miRNA.Results:There were 35 unique probes showed significant differences (p-value... |
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