| Summary: | 碩士 === 輔仁大學 === 生命科學系碩士班 === 102 === Diabetes has become one of the top ten leading cause of death recently. Diabetes can cause many complications, one of which is diabetic nephropathy, 20% to 40% of patients with diabetes lead to kidney failure, and accounted for 40% of the dialysis population. Diabetes is a group of metabolic diseases in which a person has high blood sugar. High blood sugar will lead to formation advanced glycation end products (AGEs). In previous studies, AGEs bind to its receptor RAGE, ROS generation and inflammation reaction will further lead to the diabetic nephropathy. Glucagon-like peptide-1(GLP-1) is an incretin and major source of GLP-1 in the body. GLP-1 as a gut hormone is secreted from intestinal L cell.GLP-1 can modulate insulin and glucagon to decrease blood glucose during hyperglycemia. Previous study presented that GLP-1 via GLP-1R and it could work as an anti-inflammatory agent against AGE by reducing RAGE expression via activation of cyclic AMP pathways.AMP-activated protein kinase (AMPK) is a key enzyme to maintain and regulate cellular energy balance, and AMPK activation can regulate multiple cellular signal transduction pathways. Activation of AMPK has been shown to reduce visceral fat content, cholesterol synthesis and increase hepatic glucose disposal. Thus, AMPK has been considered as a molecular target for type II diabetes. Previous study showed activate AMPK pathway to inhibit cell proliferation and fibronectin secretion in rat mesangial cells. The laboratory had previously study that the inflammation-related proteins, such as RAGE, NIK or NF-κB and cytokines TNF-α, IL-6 induced by high glucose or advanced glycation end products was attenuated by PPARδ agonist and EGCG, indicated that PPARδ agonist and EGCG have ability to improve diabetic nephropathy.Another complications of diabetes is wound healing.Hhyperbaric oxygen therapy is effective in helping wounds heal. Studies showed that hyperbaric oxygen therapy is also effective for treating acute nephropathy. Therefore, this study aimed to test PPARδ agonist, EGCG and a novel AMPK activator (HybriMore) and hyperbaric oxygen therapy in regulating GLP-1 or GLP-1 receptor for kidney protection. The beneficial mechanism of drugs and hyperbaric oxygen therapy will also be studied in in vitro diabetic nephropathy model. In this study: (1) HybriMore can improve the Normal Rat Kidney cell (NRK) hypertrophy, which cause by AGEs. (2) HybriMore can activate AMPK, and it probability by inhibit the downstream pathway of GLP-1R to improve the cell hypertrophy.(3) Although the effects of hyperbaric oxygen are not significant in the experiment, but hyperbaric oxygen therapy in the preliminary tests which can reduce the damage to cells which cause by AGEs and hyperbaric oxygen therapy can restore cell viability. Even though the pathway has not been well studied, this study provides molecular and clinical evidences that HybriMore have the potential as a therapeutic drug in diabetic nephropathy.
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