Protective Effect Of Resveratrol On High Glucose Induced Cell Apoptosis And The Underlying Mechanism

Aim: Diabetic nephropathy is one of the most seriously complications and the most cause of mortality of diabetes.Now still lack of effective treatment of DN.Excessive accumulation of extracellular matrix of kidney extracellular matrix(excessive accumulation of extracellular matrix,ECM),thickening of tubulointerstitial compartments and hyalinization of intrarenal vasculature are the characteristics structure changes of diabetic nephropathy,and oxidative stress generation of reactive oxygen species(reactive oxygen species,ROS)play a central role in synthesis and degradation of the ECM of glomerulus and renal tubule interstitial.Oxidative stress plays an important role in the pathogenesis of diabetic nephropathy.Nuclear factor erythroid 2-related factor 2 is the activator of antioxidant responsive element.Nrf2-ARE is the most important endogenous antioxidant stress pathway.Role of Nrf2-ARE in the development of diabetic nephropathy has been widely concerned.Resveratrol is a kind of natural polyphenols alcohol compounds,widely exists in a variety of plants such as grape seeds,peanuts,giant knotweed,have anti-inflammatory,antioxidant and anti-aging and other pharmacological activities.Resveratrol can obviously reduce the level of albuminuria and creatinine clearance of DN rats,it can effectively reduce the high renal perfusion and filtration of DN rat;Resveratrol can effectively reduce the expression of kidneys ? type collagen,protein fiber connection,transforming growth factor beta 1,original connective tissue growth factor,fibrinolytic enzyme activators inhibitor-1,resulting in effectively reduced renal fibrosis degree of diabetic rats.In our study,high glucose was used to stimulate HK-2 to apoptosis,and illustrate the protective effect of resveratrol on HK-2 apoptosis and the underlying mechanism.Methods: The vitality of HK-2 was observed by MTT;The apoptosis of HK-2 cells was detected by caspase-3 vitality and Hoechst staining.The level of reactive oxygen species in HK-2 cells was detected by fluorescent probe of DCFH-DA;The expression of Nrf2 mRNA were analyzed by Real-time PCR.The protein expression of Nrf2 was detected by Western Blot.Results: High glucose significantly decreased the vitality of HK-2 and promoted apoptosis of HK-2 in time-dependent manner,accompanied by reduced Nrf2 mRNA and protein expression.In cultured HK-2,high glucose markedly increased intracellular ROS generation.10?M resveratrol significantly inhibited the effects of high glucose on HK-2 function and increased Nrf2 mRNA and protein expression.Conclusion: the protection mechanism of resveratrol maybe related to the down-regulation of ROS generation and up-regulation of Nrf2.