Effect of resveratrol on oxidative stress in diabetic nephropathy

2012-12-07 classification: efficacy and action 0 people commented that resveratrol is a kind of natural polyphenol compound existing in plants, which is found in common medicinal plants, such as cassia, Veratrum, Polygonum cuspidatum, etc it was first found in fruits and plants, especially in grapes and wine, and has a wide range of biological activities and great clinical application potential Most of the early researches on resveratrol mainly focused on its protection of cardiovascular system and anti-tumor Later, it was found that resveratrol can enhance cell viability, scavenge free radicals, improve insulin resistance and anti-inflammatory At present, relevant researches have proved that resveratrol also plays a role in diabetes This article reviews the biological properties of resveratrol and its improvement of oxidative stress in early diabetic nephropathy Resveratrol, also known as stilbene, is a stilbene, stilbene and non flavonoid polyphenol with stilbene structure Its relative molecular weight is 228.25 It is a white acicular crystal It is difficult to dissolve in water and organic solvent It can produce fluorescence under the ultraviolet irradiation with wavelength of 365nm At present, many studies have shown that resveratrol has rich pharmacological and health care effects, which can not only improve cardiovascular and cerebrovascular diseases, prevent atherosclerosis and coronary heart disease, but also protect liver, inhibit platelet aggregation, regulate lipid metabolism, anti-tumor, Immunomodulate and so on Among them, its anti-oxidation and scavenging of human free radicals in the treatment of diabetic nephropathy (DN) is one of the hot spots of current research DN is a serious chronic complication of diabetes mellitus and the main cause of ESRD in western countries A number of experiments have shown that the level of oxidative stress in diabetic patients will increase As an independent factor in the pathogenesis and development of diabetes, people pay more and more attention to it Oxidative stress refers to the excessive response of oxygen free radicals in the body when the body is subjected to various harmful stimuli When the oxidation and antioxidant system lose balance, it will lead to tissue and function damage （1） During the production of diabetes mellitus by ROS in renal tissue, due to the disorder of glucose metabolism, glucose self oxidation, non enzymatic glycosylation of protein, activation of renin and angiotension system, and metabolic stress, a large number of ROS are produced in kidney Fukami et al Showed that protein nonenzymatic glycosylation formed advanced glycation end products (ages), which combined with specific receptor molecules (RAGE) on the surface of mesangial cells, endothelial cells, monocytes / macrophages and vascular smooth muscle cells to induce a large number of ROS in cells Mitochondrion is an important organ to produce ROS The excessive production of ROS in high glucose state may be related to mitochondrial dysfunction, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the main source of ROS （2） When oxidative stress affects diabetes mellitus in diabetic nephropathy, the activity of NADPH oxidase is up-regulated under various stimulation, ROS products are produced, which cause cell damage, increase free radical production and decrease antioxidant capacity, leading to oxidative stress The mechanism of oxidative stress mediated diabetic nephropathy may include: (1) ROS attack lipid, protein and DNA, resulting in renal damage (2) In diabetic state, ROS may participate in glomerular hyperperfusion and hyperfiltration through nitric oxide (no) (3) High glucose initiates podocyte apoptosis through ROS, which reduces the number of podocytes (4) ROS mediates the changes of renal intrinsic cellular behavior caused by extracellular metabolism factors (ages) and vasoactive substances (such as angiopoietin 2 (Ang Ⅱ)), which leads to the disorder of extracellular matrix metabolism (5) Oxidative stress also causes Ca 2 + overload in renal cells, activates protein kinase (PK), affects mitochondrial function by changing oxidative phosphorylation, calcium homeostasis and protein conversion, and participates in the pathogenesis of diabetic nephropathy （1） Resveratrol has been shown to inhibit the production of ROS It has been shown that taking a certain dose of antioxidants can effectively reduce the damage of oxidative stress on diabetic body Recent studies have found that resveratrol, as an antioxidant, plays an antioxidant stress role by significantly increasing the protein level and activity of mitochondrial manganese superoxide dismutase Resveratrol is a kind of polyphenolic substance It can not only inhibit the activity of NADPH oxidase by removing ROS directly, but also protect cells from the damage induced by oxidized LDL Resveratrol can not only eliminate the activity of hydroxyl radicals, reduce the generation of oxygen radicals, inhibit the oh superoxide anion and other oxygen radicals, and protect DNA from damage, but also effectively inhibit the production of ROS in mesangial cells, enhance the antioxidant capacity of the body and reduce oxidative damage ROS can stimulate the expression of collagen I, III, IV and fibronectin in renal ECM, while resveratrol can significantly reverse the accumulation of ECM induced by high glucose （2） Resveratrol prevents the activation of NF - κ B because ROS is one of the important factors to induce the activation of NF-kB After ROS is produced by mesangial cells, PKC is phosphorylated and activated, and then NF - κ B expression is enhanced by activating mitogen activated protein kinase signal transduction pathway Ha et al found that ROS produced in high glucose state activated NF - κ B, which upregulated MCP-1 expression by promoting monocyte chemoattractant protein-1 (MCP-1) gene transcription It has been proved that ROS can damage insulin-induced phosphorylation of insulin receptor substrate, activate NF - κ B and cause inflammation NF - κ B positive products are mainly located in the nucleus, combined with intracellular inhibitors, and exist in mesangial cells On the one hand, they participate in the expression and regulation of inflammatory factors and cytokines related genes, on the other hand, they interfere with the insulin signal transduction pathway, leading to insulin resistance Therefore, NF - κ B plays an important role in the development of glomerular diseases by regulating the transcription of inflammatory factors and cytokines Resveratrol can prevent the activation of NF - κ B by interfering with the metabolism of ROS and scavenging oxygen free radicals It can also reduce the activity of NF - κ B by inhibiting the upstream pathway of NF - κ B, fight against DNA oxidative damage caused by ROS and lipid peroxidation of cell membrane, to a certain extent, reduce the inflammation and proliferation of glomerular cells, and protect renal tissue （3） Resveratrol activated adenosine phosphokinase (AMPK) AMPK is a major metabolic regulator of liver, skeletal muscle and heart, which can regulate energy metabolism When AMPK is activated, it can be used as a metabolic regulation hub, which can increase skeletal muscle's glucose uptake, enhance insulin sensitivity, accelerate fatty acid oxidation and regulate gene transcription In the kidney of diabetic rats, the expression of AMPK phosphorylation protein and the activity of AMPK decreased The activation of mTOR induced the phosphorylation of downstream proteins 4E-BP1 and ps6k and the decrease of eukaryotic elongation factor (EEF) activity mediated the early hypertrophy of kidney Chanet al Found that resveratrol can directly activate AMPK in cardiomyocytes, thus weakening the signal pathway of rapamycin target protein (mTOR), reducing the downstream protein 4E-BP1 and ps6k phosphorylation protein, delaying and improving cardiomyocyte hypertrophy Shangjing et al found that resveratrol can promote AMPK phosphorylation and improve insulin resistance Park et al found that resveratrol can promote glucose uptake by activating AMPK in C2C12 myocytes These studies suggest that the activation of AMPK pathway is the key for resveratrol to play its role in reducing blood sugar and regulating lipid （4） Resveratrol activated silent information regulator 1 (SIRT1) SIRT1 is one of the important targets of resveratrol in regulating glucose and lipid metabolism SIRT1 plays an important role in energy metabolism At present, it is believed that resveratrol's antioxidant effect is achieved by activating SIRT1, a histone deacetylase SIRT1 is a NAD + - dependent histone deacetylase, which participates in the regulation of many physiological functions in vivo, including gene transcription, energy metabolism, muscle tissue differentiation, etc., especially plays an important role in increasing insulin secretion, mobilization of peripheral fat tissue, glucose metabolism Resveratrol is an in vitro activator of SIRT1 Resveratrol can be used as SIRT1 activator to increase insulin sensitivity in a SIRT1 dependent manner and alleviate the symptoms of insulin resistance induced by high fat The decreased expression of SIRT1 protein in primary adipocytes in the pathological state of insulin resistance suggests that SIRT1 may be related to the occurrence and development of insulin resistance, while resveratrol can effectively improve the expression of SIRT1 by increasing the expression of SIRT1 Element resistance Oxidative stress plays an important role in the development of diabetic nephropathy A variety of antioxidants can delay the development of DN Resveratrol can resist oxidative stress and improve the symptoms of early DN Resveratrol has obvious antioxidant stress effect, which can avoid oxidative stress injury induced by high glucose and fat, so it plays an important role in the prevention and treatment of diabetes and its chronic complications, especially in the early stage of diabetes, delaying the development of DN and protecting kidney tissue However, although resveratrol is a natural drug with great potential, the current research is limited to animal experiments and cell molecular level, and its clinical application is relatively small, and its clinical application prospects need further study.