| Backgrounds and aimsEnd-stage renal disease(ESRD) is a global health problem,as a result of renal function with severe damage,the patients will be a series of metabolic syndrome disorders.Although the Development and popularization of blood purification by the last half a century,the Survival time of patients with ESRD has been extended,but the quality of life of patients and long-term survival is still under serious threat. Results of foreign show that Cardiovascular Disease(CVD) in patients with ESRD is the first cause of death,the incidence is as high as 60%,20-30 times higher than the general population;the Chinese Medical Association Society of Nephrology statistics also showed that nearly 70%of hemodialysis patients died of CVD.Therefore,the cause and prevention of cardiovascular complications in patients with ESRD has been the focus of domestic and foreign scholars to explore topics.The vascular calcification is popular in the ESRD patients,so the more compelling studies related.Vascular calcification includes two types:First, intimal calcification:It is a markers of atherosclerotic disease, occurred in the formation of advanced atherosclerotic plaque is commonly found in the artery lumen allows blood vessel blockage,blood flow reduction,ultimately lead to ischemia and necrosis organizations,with non-diabetic or kidney disease in the population,vascular calcification mainly in the characteristics of this type.Second,medial calcification (Monckeberg's middle calcinosis):mainly in large,medium artery calcification is characterized by smooth muscle layer,can be independent of the atherosclerotic plaque exists and is the main types of vascular calcification in patients with ESRD,it can be seen in the diabetic patients too;medial calcification in a condition known as "small-artery calcification in uremic patients",occurred in uremia,especially long-term maintenance dialysis patients,it belongs to a small artery embolization diseases,acute onset,rapid progress,high mortality, usually skin and subcutaneous arteries and arterioles of the middle calcification and intimal hyperplasia obstructive.Occurred in atherosclerotic plaque calcification can increase in the membrane brittle plaque calcification in general does not affect the arterial lumen diameter,but can increase the hardness of blood vessels,reducing its compliance,so that changes in hemodynamics.Such patients with systolic blood pressure usually increased,decreased diastolic blood pressure, pulse pressure increased,causing left ventricular hypertrophy and decreased coronary perfusion,culminating in myocardial ischemia and necrosis,congestive heart failure,arrhythmias and so on,threats the life of patients.Previous view that vascular calcification is a passive process,with the age or the formation of atherosclerotic plaque,but the clinical and histological findings indicate that some bone metabolism-related genes and proteins directly involved in vascular calcification in uremia the occurrence and development of the process,in recent years,the latest evidence that vascular calcification is similar to bone and cartilage formation process of active regulation,the main features of the vessel wall cells,especially In particular,vascular smooth muscle cells(VSMC) bone-like changes in the adjustment process in the initiative,showing matrix vesicles,alkaline phosphatase activity increased,and non-collagen extracellular matrix proteins such as osteopontin and other osteoblast-like cell phenotype characteristics.Osteopontin(OPN) as a lining of acid phosphatase protein adsorption to hydroxyapatite in the organization play an important role in mineralization,is the differentiation of osteoblast markers.Recent studies have found that OPN is a natural body of ectopic calcification inhibitor,in the absence of OPN to protect the mice,calcification rate is 4-5 times that of wild mice.Study points,OPN not only inhibits the deposition of calcium phosphate,and by blocking hydroxyapatite crystal growth,induced by carbonic anhydraseⅡin the expression of monocyte to promote extracellular acidification of the environment,active promotion of the dissolved calcium.Under certain conditions, macrophages,T lymphocytes and vascular smooth muscle cells,epithelial cells can be generated,such as OPN,to a maximum of macrophages.Most of the normal soft tissue did not express OPN,and in atherosclerotic plaque of diabetic vascular lesions,uremic small-artery calcification disease and arterial calcification in the flap but there are a lot of OPN. OPN and the relationship between uremic vascular calcification has not yet entirely clear,some people have done bovine vascular smooth muscle cells cultured in vitro experiments,they found that P-glycerol phosphate in the creation of high-phosphorus conditions,the cells can produce calcification,but low-medium concentrations of OPN(0.05 to 5 ug/mL), calcium deposition can reduce the emergence At the same time.other experiments have been proved to inhibit OPN role calcification,but the exact mechanism is still not clear.Osteoprotegerin(OPG) is a newly discovered cytokine,can inhibit osteoclast-specific cells are osteoblasts and stromal cells secreted glycoprotein.The biological role of OPG to block the expression of osteoblast RANKL,also known as OPGL(Osteoprotegerin ligand, NF-KB-activating factor receptor ligand) and the expression of osteoclast RANK(Receptor activator of NF-KB,NF-KB the activated receptor),thereby inhibiting osteoclast differentiation and activation.Clinical observation of vascular calcification and osteoporosis often occur at the same time,OPG and vascular calcification may be the common pathogenesis of osteoporosis key.That is,patients with osteoporosis often exist atherosclerosis and vascular calcification,This suggests that calcium from bone metastasis to the artery wall may be the cause of an important artery causes hardening of the arteries.Recent studies show that apart from the traditional risk factors such as old age,high blood pressure,abnormal lipid metabolism,other factors such as phosphorus level,chronic inflammation,vitamin K/warfarin MGP impact on,E-selectin,gene polymorphism,heptin such as can be involved in calcification,and the process affected by a variety of hormone and cytokine regulation,OPG is one of the important factors.Are of the view that hyperphosphatemia,chronic inflammation of vascular calcification may be the most important contributing factor in ESRD patients,,clinical studys of cardiovascular disease in uremic patients and is closely related to increased blood calcium and phosphorus.High P-induced cardiovascular calcification of the adjustment mechanism of the molecular level has become a hot current study,but some studies suggest that high phosphorus vascular calcification in uremic patients is an independent risk factor. At present,vascular calcium in uremic patients on the study of mechanisms for more on the phosphorus,OPN,OPG and vascular calcification in the relationship between the study focused on in vitro cell culture and animal experiments,but on vascular calcification in uremic patients with OPN,OPG and the relationship between phosphorus research,yet few and far between.The purpose of this study is disturbed in uremic patients with calcification of arteries carry out classification,analysis of OPN, OPG expression,analysis of vascular calcification and OPN,OPG and the relationship between clinical indicators.Study Object and MethodsCollected 62 cases of flexible organization in uremic patients whith were cut from the forearm,the first flexible arterial anastomosis fistula of the blood purification center of The First Affiliated Hospital of Zhengzhou University in May 2008～July 2008,The First Affiliated Hospital of Zhengzhou University.32 cases were male,30 cases were women,aged 17 to 76 years old,the average age of 46.5 years old.All patients preoperatively calculated by Schwartz formula creatinine clearance＜15ml/min,1.73m~2,of which 42 were accepted hemodialysis and 10 peritoneal dialysis treatment,of which 27 cases of diabetic nephropathy, 35 non-diabetic nephropathy cases.Started renal replacement therapy duration from 1 to 60 months(average 12.5±12 months),all routine testing in patients with preoperative serum calcium,phosphorus,lipids, liver and kidney power,weight,height.62 cases were fixed by 10% formaldehyde,embedded in conventional dehydration for continuous slicing 3um.With alizarin red staining,analysis of vascular calcification in accordance with the degree of calcification grading;by immunohistochemical SP method OPN,OPG expression.OPN,OPG,calcium, phosphorus,lipids,liver and kidney work,body mass index,dialysis time, such as indicators of data were SPSS(10.0 version) for statistical analysis.Calcification in accordance with the degree of classification, whether classification of diabetes statistics,distribution of information to compare the use of group one-way ANOVA,the data do not meet the normal distribution is used non-parametric tests,correlation analysis using Pearson correlation(distribution) and Spearman correlation(non-normal distribution),the rate of using X~2 test comparison.To a=0.05 as the standard test.Results1.Calcification stained 62 cases of torsion in patients with end-stage renal disease in the artery specimens,and the existence of 15 cases of calcification,the incidence of 24.2%,of which four cases of severe calcification,calcification in 11 cases of mild to moderate,both occurred in the vascular membrane.2.Immunohistochemistry 15 cases of calcification in arteries of the flexible membrane in the cytoplasm of smooth muscle cells are OPN,OPG expression,in the absence of staining of vascular calcification in specimens,30.5 percent of the specimens are still at least OPN,OPG one types of positive expression.Severe calcification group of OPN,OPG expression were significantly higher than those without calcification group,but mild to moderate calcification and severe calcification was no significant difference between(P＞0.05).3.Calcification and clinical indicators of phosphorus,calcium and phosphorus product,body mass index and the degree of calcification was a positive correlation.Severe calcification group of dialysis longer than non-calcified group was significantly longer(P＜0.05). Calcification of the inter-group differences in other indicators were not statistically significant(P＞0.05).Uremia due to diabetic nephropathy the incidence of vascular calcification is not higher than other primary diseases(square=0.078 degrees of freedom=1 p=0.780). 4.Immunohistochemical indicators and clinical indicators of OPN and phosphorus,BMI,dialysis time was a significant positive correlation, OPG and phosphorus,calcium and phosphorus product,dialysis time was positively correlated.Conclusion1.Uremia in patients with vascular calcification of the radial artery in the membrane is characterized by calcification and take the initiative to,similar to the calcification process of osteoblasts.2.Uremia of the radial artery in patients with vascular calcification and hyperphosphatemia is closely related to abnormal calcium metabolism may be to promote artery calcification in the basis of the initiative.3.These is no significant difference in the incidence of vascular calcification between the diabetic Uremic and non-diabetic uremic patients.4.Osteoprotegerin may be involved in the development process to prevent calcification,but not enough to completely prevent the calcification. |
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