| Erectile dysfunction (ED) is the inability of a man to achieve or maintain an erection sufficient for his sexual needs or the needs of his partner for more than three months, which is caused by lack of blood filling in the penis by a variety of reasons. Erectile dysfunction is a common urinary and andrology disease. With the improvement of our living standard, more and more attention has been paid on erectile dysfunction now. About 152 million men worldwide suffer from erectile dysfunction currently by epidemiological survey, especially in men over the age of 45, whose risk of suffering from erectile dysfunction is significantly higher than Youngers. It will be 322 million men suffering from erectile dysfunction worldwidely by 2025. DiabeteSmellitus (DM) is a metabolic disorder caused by a variety of causes of disease, characterized by chronic high blood sugar, reduced insulin secretion or underutilization of insulin, resulting in metabolic disorders of carbohydrate, fat and protein, which then caused chronic injury or failure of many organs. There are diabetic patients all around the world. The incidence and prevalence of diabetes increased gradually nowadays. With the development of social and economic, the increasing tendency of incidence of diabetes becomes more and more obvious in recent decades. Diabetes has become a global public health problem in 21st century now. Erectile dysfunction is a common complication of diabetes, which is closely related to diabetes. The incidence of erectile dysfunction in diabetic patients is 3 times than that in general population. WHO reports that 50% to 75% of diabetes patients suffer from different degrees of erectile dysfunction. Diabetes mellitus induced erectile dysfunction (DMED) has a long and complexity course, the incidence and pathogenesis has not yet been fully understood. Normal penile erection is a process of increasing inflow of arterial blood, and decreaseing outflow of venous blood flow in the penis which increased the pressure of the corpus cavernosum with the smooth muscle relaxation. Any pathological process effect on the increasing blood volume or on the relaxation of corpus cavernosum smooth muscle can lead to erectile dysfunction. DMED primarily caused by the combined effect of the organic damage and the psychosocial factors in the patients.Macroangiopathy of diabetes makes blood flow to the penis cavernous decreased, and the micro-vascular disease of diabetes leads ischemia, hypoxia, decreased oxygen saturation to the penis. And then reduce the number of smooth muscle cells in corpus cavernosum, as the fibrosis of corpus cavernosum and the flexibility of proteins and albuginea collagen increased, which leading irreversible damage to the cavernous smooth muscle's function, and then led to erectile dysfunction. The current research of DMED focuses on the pathogenesis of blood vessels, nerves, cavernous smooth muscle of the penile in diabetes and other aspects of organic damage, now more and more attention has also been paid to the social and psychological factors. Most of current research in DMED at home and abroad emphasis on aspects of serum hormones, such as testosterone, estradiol, sex hormone receptors. The research on DMED in molecular biology now is limited to animal models, there is little research on susceptibility genes at home and abroad about DMED, and less research reported on the molecular biology of human DMED.Bioinformatics is a multi-disciplinary subject that has emerged from the application of computer science, information science and mathematics to problems in biology and the life sciences, especially those involving large data sets such as genomes. Highly inter-disciplinary in nature, bioinformatics has attracted biologists, physicists, mathematicians, chemists and computer scientists. Bioinformatics encompasses all aspects of biological information acquisition, processing, storage, distribution, analysis and interpretation. It makes the integrated use of mathematics, computer science and biology tools to achieve the biological meaning of the data contained in the data as its purpose. The developement of Gene chip technology and bioinformatics technology opened a new way for us to study the pathogenesis of DMED. As the high-throughput gene chip technology developed and widely applied, vast amounts of gene expression data appeared. fortunately, the development of bioinformatics also provide strong technical support for storage, processing, analysis and integration of these large data. Biomedical literature mining and bioinformatics analysis have become a focus in the field of biomedical research now. In this study, Affymetrix Gene Chip arrays from the Gene Expression Omnibus (GEO) was used to examine the alterations in penile gene expression between streptozotocin-induced diabetic rats and littermate controls. This data set was analyzed with GeneSifter microarray analysis software. In order to take advantage of the microarray expression data stored in gene expression database GEO combined with some knowledge of biology to better understand the pathogenesis of diabetic erectile dysfunction and provides the scientific aspects of clues for further study.The main content of this study divided into three chapters.In the first chapter, we give an overview on gene chip data mining and bioinformatics. This part introduces the concepts of bioinformatics, gene chip, Gene Expression Omnibus, bioinformatics analysis of gene chip data and the application of softwares commonly used for microarray data analysis. Bioinformatics is an interdisciplinary field that blends computer science and biostatistics with biological and biomedical sciences such as biochemistry, cell biology, developmental biology, genetics, genomics, and physiology. Bioinformatics makes full use of mathematics, computer science and biology tools to achieve the biological meaning of the data contained in the data as it's purpose. Gene chips, also known as "DNA microarrays", refer to nylon membranes or glass slides that contain either synthetic oligonucleotide DNA or cDNA probes. Each probe has unique sequences that correspond to a specific gene. Gene Expression Omnibus referred to as GEO, was founded in 2000, is the largest and fully open database with high throughput molecular abundance, GEO's main storage of gene expression is hybridization array data. We will get a range of fluorescence intensity signals after the hybridization of the Gene chip between samples. These signals will be extracted by the software installed in the scanner. And the relevant biological knowledge is to be got after the gene chip data was mined and analyze. The software GeneSifter used in this study for microarray data analysis is just one of the microarray analysis softwares.In the second chapter, Affymetrix Gene Chip arrays from the Gene Expression Omnibus (GEO) was used to examine the alterations in penile gene expression between streptozotocin-induced diabetic rats and littermate controls. This data set was analyzed with GeneSifter microarray analysis software. We also give an example to demonstrate how to use the Genesifter to analyze the alterations in penile gene expression between streptozotocin-induced diabetic rats and littermate controls (data set GSE2457 from GEO database). The development process of DMED includes many kinds of molecules changes, and these molecules changes can be reflected in gene expression level. With the development of modern molecular biology and bioinformatics, the use of bioinformatics techniques to analyze the gene expression between normal erection and DMED penile tissue provides a new approach for the pathogenesis of DMED study. These datasets got from penile gene expression between streptozotocin-induced diabetic rats and littermate controls was analyzed by GeneSifter microarray analysis software. After filtering the data,661 differentially expressed genes were identified. Gene Ontologe and KEGG analysis showed that the genes correlated with wound healing, triglyceride metabolic process, cell proliferation and other important biological processes, and some pathways also involved, such as fatty acid metabolism, neurodegenerative disorders, ECM-receptor interaction etc. We found that some genes such as klf5, cp, collagen bag etc play an important role in the pathophysiology of diabetes-induced ED.In the third chapter, We test the apoptosis in Corpus cavernosum smooth muscle cells of normal rats and rats with diabetic erectile dysfunction to study how apoptosis plays a role in the pathogenesis of DMED. It is obvious from the experimental results that in the diabetic state, the apoptosis of CCSMC in diabetic rats with erectile dysfunction is faster than normal rats, which suggests that the apoptosis of CCSMC reduced the number of CCSMC, led to systolic and diastolic disorders of the penis, and finally causing ED. This may be an important mechanism of pathogenesis in rats with DMED. Combining the results of bioinformatics, we suggested that in the diabetic state, the body produces a large amount of oxygen free radicals (especially ROS), which activated the growth factor receptors through the JNK and p38 signal transduction pathways, causing the Ras-Raf-ERK pathway activated, and started the process of caspase dependent apoptosis, which induced the apoptosis of CCSMC, reduced the number of CCSMC, and caused systolic and diastolic disorders of the penis, eventually led to the occurrence of ED. But the precise regulatory mechanism of DMED is still unclear, further experimental studies have needed to be carried out.Bioinformatics can analyze gene chip data and internal information effectively. It will offer a new view for broadening the scope of candidata genes and pathways that may be relevant to the pathophysiology of DMED as well as highlighting the potential complexity of this disorder. |
