The Protective Effects Of Resveratrol On High Fat And High Glucose Diet Induced Renal Injury In Rats

Objective: Researches suggested that long-term high fat and high-glucose diet can cause lipid and glucose metabolism disorders in body, which may cause clinical diabetes and hyperlipidemia. Increased reactive oxygen in vivo plays an important role in the happening and development of the above diseases. While antioxidant enzymes system in vivo such as superoxide dismutase, glutathione peroxidase activities declined as a result of the long-term oxidative stress. High fat and high-glucose diet caused the early stage of the metabolic syndrome, the change of which is similar to diabetes, while oxidative stress played an important role in the occurrence of diabetic nephropathy, one of the main complications of diabetes.Renin-renin-angiotensin-aldosterone system is the endocrine system, which directly related to kidney disease. The increased effects of angiotensin and aldosterone are the main factors that cause kidney diseases. Several studies confirmed angiotensinⅡactivity in kidney is increased in patients with diabetes. AngiotensinⅡis the center of the renin-angiotensin-aldosterone system, angiotensinⅡcan induce cells synthetic and secrete fibrosis factors such as plasminogen activator inhibitor-1(PAI-1) which promote fibrosis and related signal transduction pathway molecules (including PI3K/Akt signal pathway molecules) which caused glomerular sclerosis. At present PI3K/Akt pathways have been found playing a role in the process of fibrosis caused by a wide variety of cell factors, studies showed that polyphenols with renal protection effects and can inhibit PAI-1 and PI3K expression. Resveratrol, a polyphenol compound mainly exists in grapes, LiLu and other plants, as a kind of natural antioxidants can improve high fat and high-glucose induced oxidative stress. Therefore, this experiment will explore the effects of resveratrol on high glucose and high fat diet rats'renal protection and its action on influence PI3K, PAI-1 express in the kidney, and further understand its possible antioxidation, antifibrosis role.Methods: 60 Male Wistar rats divided into 5 groups: normal control group (Con), high fat and high-glucose group (H), high fat and high-glucose diet plus resveratrol co-treatment group (low, medium and high dose resveratrol group R1, R2, R3). Con group rats were fed normal diet, H group and resveratrol dose group rats were fed high fat and high-glucose diet, or plus oral administration of resveratrol(with doses of 50mg/kg.bw, 100mg/kg.bw, 150mg/kg.bw) dissolved in the vegetable oil. (high, medium and low doses of resveratrol group), H group rats oral administration of vegetable oil in the volume, weighing animal weight regularly. All rats were killed after 13 weeks, separated serum was stored in -80℃, and serum glucose (FPG), cholesterol (TC), triglyceride (TG) were determined. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) content were measured in renal tissue extracts. Fluorescence real-time quantitative polymerase chain reaction method was used to detect renal cortical PI3K, PAI-1mRNA expression levels and western blotting was used to determine protein expression levels of PI3K, PAI -1.Results: (1) After 8w high fat and high-glucose diet, compared with Con group, the H rats'body weight increased significantly, R2, R3 group rats'body weight were lower than the H group. 13w when rats from different groups were similar with 8w in body weight. (2) Compared with Con, H group rats whose FPG levels were significantly increased, compared with H group rats, R2 rats FPG levels were significantly reduced. Compared with Con, H group rats whose plasma TC and TG levels were significantly increased, compared with H group rats, R2,R3 rats plasma TC and R2 group rats plasma TG were significantly reduced. (3)H group rats'renal cortical MDA content increased significantly than Con group, high fat and high-glucose diet plus resveratrol co-treatment group rats'renal cortical MDA content reduced compared with H group. While H group rats compared with Con, kidney T-AOC, T-SOD were significantly reduced, resveratrol improve T-AOC, T-SOD and GSH-Px levels. (4) Compared with Con rats, higher renal PAI-1 mRNA and PI3K, PAI-1 protein expression levels were observed in H group rats, while decreased expression of PI3K, PAI-1 mRNA and protein were observed in the kidney of the co-treated with resveratrol rats.Conclusions: High fat and high-glucose diet can cause significant oxidative stress in rat kidneys, which may be involved in the occurrence of renal damage. Resveratrol has protective effect on the high fat and high-glucose diet induced oxidative renal injury in rats.