| Diabetic nephropathy is the most common microvascular complications of diabetes one has seriously affected the quality of life with diabetes. The pathogenesis of diabetic nephropathy is uncertain, in recent years, more and more studies have shown that in many pathogenesis, oxidative stress is an important common mechanism.Oxidative stress refers to as reactive oxygen (reactive oxygen species, ROS) and reactive nitrogen groups (reactive nitrogen species, RNS) such as over-activity of molecular generating and/or removal decrease, leading to ROS generation and anti-class balance between oxidative defense function disorder. Thus, we come to oxidative stress in diabetic patients with a mechanism mainly.Which, ROS include free radicals such as superoxide anions (O2-), hydroxyl radical(OH) and non-free radical groups such as hydrogen peroxide (H2O2) and hydrochloric acid (HOCl). RNS include free radicals like a nitric oxide (NO) and nitrogen dioxide (NO2-), also non-radicals such as catalase (ONOO-), alkyl peroxide (RONOO)[4]. Meanwhile, two types of body antioxidant system, one is antioxidant enzyme systems, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), etc. another non-enzymatic antioxidant systems, including vitamin C, vitamin E, glutathione, melatonin,α-lipoic acid, carotenoids, trace elements copper, zinc, selenium (Se) and so on.Oxidative stress in patients with diabetic nephropathy mechanisms: 1, kidney tissue reactive oxygen species increased: 1) OS enzymatic reaction Source: Diabetic nephropathy enhanced when the enzyme activity of groups of sources, including nitric oxide synthase (NOS), NADH / NADPH oxidase and xanthine oxidase. All NOS isoforms require five cofactors, and prosthetic group, the lack of it if NOS L-arginine subunit or a synergistic factor,. NAD (P) H oxidase is a membrane associated enzyme, composed of five subunits, is also an important source of O2-production. Under normal physiological conditions, the oxidation of xanthine oxidase activity more difficult to predict out, but the electron spin through the sensitive technology has been proven in animal models of typeâ… diabetes, xanthine caused a large number of reactive oxygen molecules; 2) ROS sources of non-enzymatic reaction: non-enzymatic oxidation of glucose to be aroused from the oxidation of biochemical reactions. Glucose can be produced through self-oxidation and OH radical, in addition, glucose and protein through non-enzymatic reactions, Amadori rearrangement after the formation of advanced glycation end products (AGEs), ROS in this process through multiple steps to produce. In the case of high blood sugar, glucose by polyhydroxy compounds (sorbitol) pathway is enhanced metabolism, this process also enhances O2-production. And high blood sugar can activate glomerular podocyte metabolism of arachidonic acid 12-lipoxygenase pathway, but the 12 - lipoxygenase activation also can promote ROS generation. 3) mitochondrial Source: mitochondrial respiratory chain enzymes of reactive oxygen molecules into non-students, another important source. Glucose into the cells, generated through the glycolytic pathway of reduced nicotinamide adenine dinucleotide (NADH) and pyruvate, NADH by malate-aspartate shuttle mechanism into the mitochondria. After pyruvate into the mitochondria through the tricarboxylic acid (TCA) cycle generates NADH and flavin adenine dinucleotide reduced form (FADH2), mitochondria NADH and FADH2 to the respiratory chain can facilitate the transmission of electronic generation of ATP. 2, renal tissue oxygen scavenging activity to reduce: 1) non-enzymatic reduction of antioxidant: glutathione (GSH) is a valley, composed of cysteine and glycine tripeptide. GSH is an important intracellular reducing agent, GSH on hydrogen, the glutathione peroxidase catalyzed reduction of cells can be generated by H2O2, it turned into H2O, while GSH is oxidized into GSSG, after are again in glutathione reductase and NADPH to catalyze the regeneration of the GSH. High glucose conditions, the number of kidney cells and GSH metabolism change is one of the mechanisms to place OS. Vitamin C (Vit C) is another important body of non-enzymatic antioxidant molecules, Vit C in the body in two forms, namely, dehydroascorbate (DHA) and ascorbic acid (AA). Speculated that the high glucose, can inhibit the transport DHA, DHA reduced within the cells, resulting in an organization to reduce the use of Vit C, renal cell antioxidant ability. 2) changes in antioxidant enzyme activity: physiological state, the renal tissue antioxidant enzyme system consists mainly of Mn-superoxide dismutase (Mn-SOD, located in mitochondria), Cu, Zn-superoxide dismutase (Cu, Zn-SOD, located in the mitochondria), catalase (CAT) and glutathione peroxidase (GSH-Px). Now more inclined to view: Early in the DM and kidney tissue part of the compensatory activities of antioxidant enzymes increased, and, with DM duration of the extension, its activity gradually decreased, eventually led to the occurrence of renal tissue OS. However, activity of these enzymes in renal tissue, DM variation in specific, has no unified conclusions, Dan has more Guonei Wai Yan Jiu Qing Xiang's view yes: the DM Zaoqi, You Yu Gao for stimulating blood sugar, kidney antioxidant within the Bufen compensatory increase in enzyme activity, but with extended duration and the severity of DM increased, the activity of some antioxidant enzymes will be gradually reduced antioxidant capacity decreased, eventually led to the occurrence of renal tissue OS. 3, renal tissue damage induced by oxidative stress mechanism: 1) ROS on vascular permeability and glomerular hemodynamics: a large number of studies have shown that early in the DM, the glomeruli can occur with high pressure hyperperfusion and hyperfiltration as the characteristics of the hemodynamic change is an important pathogenesis of DN. 2) ROS on renal cell damage: renal cell antioxidant enzymes to reduce, such as superoxide dismutase, glutathione peroxidase, and catalase antioxidant enzyme glycation or oxidation occurs, so that renal the antioxidant capacity decreased, the key enzymes and intracellular transport protein Na-K-ATP inactivation of the enzyme. 3) ROS within the cells of the kidney outside the base effect: increase in extracellular matrix production and/or removal from a reduction in glomerular basement membrane thickening, mesangial broadening and interstitial fibrosis is the pathological characteristic DN change. 4, ROS, and DM state the occurrence of renal inflammation: diabetes in the presence of high glucose, blood disorders can damage the kidneys dynamics inherent in cells, cell damage and release of inflammatory chemokines, leading to filter out white blood cells to the injury site and activation, At this time, such as inflammation of the mechanism of removal was inhibited, the white blood cells confined to the site of injury. If not treated, filter out white blood cells increased local proliferation and activation of the release of more inflammatory chemokines, to further increase the incidence of inflammation, while the release of inflammatory mediators, such as tumor necrosis factor-α(TNF-α) and platelet- derived growth factor (PDGF), increased intrinsic renal cell injury, and promote renal fibrosis. Diabetic state, several factors led to the aggregation of renal tissue ROS increased, while the ROS accumulation but also in many ways led to the development of diabetic nephropathy.Choice in our hospital from January 2009 to March 2010 60 patients hospitalized for T2DM subjects, respectively, in accordance with Urinary albumin excretion rate were divided into A group (UAER<300mg) and B group (UAER≥300mg), another choice 30 age-matched healthy people as control group. Record sex, age, measuring patient height, weight, and calculate body mass index, measuring fasting blood glucose, glycated hemoglobin levels, triglyceride, total cholesterol, urea nitrogen, creatinine, nitric oxide, malondialdehyde, superoxide dismutase. The results showed that type 2 diabetes, serum nitric oxide, MDA concentration was significantly higher than the control group, the difference was statistically significant (P<0.05), 2 diabetic group, serum superoxide dismutase were significantly lower thanhealthy control group, the difference was statistically significant (P<0.05).Where, B levels of serum nitric oxide, the highest concentration of MDA, compared with A significantly (P<0.05), B levels of serum superoxide dismutase concentration in the lowest compared with the A groupsignificantly higher than (P<0.05). And malondialdehyde and superoxide dismutase was negatively correlated with statistical significance (P <0.05). In this study, by determining the negative correlation between MDA and SOD in support of oxidative stress in patients with diabetic nephropathy the major mechanism that the body anti-diabetic patients had higher levels of oxidation and free radical scavenging ability of the body weakened. |
