The prevalence of diabetes mellitus increases annually. Diabetic nephropathy is the most serious microvascular complication in diabetes mellitus. In recent years, researches show endoplasmic reticulum (ER) induces stress when cells encounter abnormal environment and injury. Finally ER stress lead to cell apoptosis. ER stress is one of important factor in diabetic nephropathy. So far, many studies explored compounds and drugs improving diabetic nephropathy. Activation of AMPK pathway decrease intracellular reactive oxygen stress and inhibit mTOR expression. Statins improve inflammatory cytokines and inhibit inflammation. Resveratrol is proved the anti-inflammatory and anti-oxidant effect. Some studies showed above compound can improve diabetic nephropathy. Till now, the role of above compound on ER stress in diabetic nephropathy is still unclear. The study will evaluate the role activation AMPK, stains and resveratrol in ER stress. In vitro study, cells will divide normal glucose group, high glucose group, and osmotic control group. GRP78 reporter plasmids are transfect to mesangial cells and renal tubular cells. The cell are incubated with AICAR, statins and resveratrol in different groups. We will observe the expression of GRP78- luciferase and western blotting. In vivo study, C57BL6 mice will divide control group, high fat diet group, type 1 diabetes group and type 2 diabetes group. The mice will be intraperitoneal injection of AICAR, or oral statins, or oral resveratrol for four or eight weeks. We will observe the GRP78 change in the kidney after treatment. We hope to find out the resolving method of improving diabetic nephropathy.
|Effective start/end date||8/1/11 → 7/31/12|
- diabetic nephropathy
- endoplasmic reticulum stress
- AMP-activated protein kinase