活性羰基化合物损伤β细胞及其机理研究-药用资源化学专业论文.docxVIP

ABSTRACTBackground ABSTRACT Background and Aims：As people’S living standards improve，the incidence of obesity and diabetes is rising rapidly on a global scale．In 20 1 4，the World Health Organization proclaimed that 2．8 million people died from overweight or obesity—related diseases each year，and obesity is a major killer of human health．Obesity is an important risk factor for diabetes．So far，there is still no way to heal diabetes mellitus，the disease has become increasingly popular in the crowd．In 20 1 1，about 36．6 million people with type 2 diabetes throughout the world．It is estimated that the total number of diabetics will increase to 5 5．2 million by 203 0， and about 48％of patients concentrated in India and China．Type 2 diabetes not only brings great agony to patients，but also causes a substantial economic burden to their families and society，and do great harm to be human．Numerous researches show that carbonyl stress plays an important role in the pathogenesis and development of diabetes and its complications．Islet beta cell埘ury is one of the main characteristics of the diabetes．But the role of carbonyl stress caused by hyperglycemia and hyperlipidemia，in the signal path of beta cell injury is unclear．In this research，to build cell model of pancreatic p cell injury，INS-1 E treated with 4-HNE．The model simulates toxicity of hyperlipidemia，which high blood lipid damage islet beta cell．And explore the influence of 4一HNE on III 万方数据 signaling signaling pathway of p cell． Methods：INS一1 E cells treated、vitll 4一HNE to build islet D cells injury model on the cellular level．Cell growth and proliferation was determined by MTT assay and BrdU staining．Based on the model， TUNEL were used to detect cell apoptosis．After INS·1E treated with 4-HNE，the change in relative gene transcript and protein expression were assess by Real-time PCR and western blotting，respectively． Results：1．INS-1 E was treated by 1 2 hours with active carbonyl compound 4-HNE．In 50vM and above concentr