| Objective:The cardiovascular disease is the most common cause of death in patientswith uremia. According to the data system for renal disease in the UnitedStates, almost50%of end stage renal disease (ESRD) patients die ofcardiovascular disease. Elastin degradation is an important determinant ofarterial stiffness and is associated with all-cause mortality. Elastin degradationis mediated by several proteases, including matrix metalloproteinase2. Therelationship between vascular stiffness and MMP-2is not clear. Wedetermined to explore the relationship between vascular stiffness and MMP-2in chronic renal failure rats, provide targets for clinical treatment.Methods:1Twnety healthy，clean level, male, seven-week-old SD rats werepurchased from animal experiment center of Hebei Medical University. Theseanimals were fed with a standard pellet chow and were given tap water adlibitum during an acclimation period of1week.2Rats were devided into3group: normal control group(6), chronicrenal failure group(7) and chronic renal failure group with vascularcalcification(7). These animal were given tap water ad libitum during anacclimation period of1week. After the acclimatization period, normal controlgroup:0.5%methylcellulose (6ml/kg) was given orally to the animals once aday for1-3weeks.0.5%methylcellulose (6ml/kg) was orally administered for4-8weeks (three to four times a week). chronic renal failure group: an adeninesuspension (100mg/mL adenine sulphate in a0.5%methylcellulose solution)was given orally to the animals once a day at an oral dose of600mg/kgadenine (6mL/kg) for3weeks.0.5%methylcellulose (6ml/kg) was orally administered for5weeks (three to four times a week). chronic renal failuregroup with vascular calcification: an adenine suspension (100mg/mL adeninesulphate in a0.5%methylcellulose solution) was given orally to the animalsonce a day at an oral dose of600mg/kg adenine (6mL/kg) for3weeks. Activevitamin D3was orally administered at dosages of200ng/kg for5weeks (threeto four times a week).3Kidney were stained with HE stain to identify structural modification ofthe kidney. In order to determine whether to establish the rat model withchronic renal failure, we test serum urea nitrogen and creatinine. Aorta werestained with EVG stain to identify the elastin change. Using RT-PCR andimmunohistochemical methods to detect the expression of MMP-2and cbfa1.Aorta were stained with von Kossa stain to identify the calcification. Calciumcontent was determined using atomic absorption spectrophotometry.4All of the data were analyzed by SPSS13.0statistical analysissoftware，experimental results were given asx±s, between the two groupswere compared by t test, many groups were compared with single factoranalysis of variance (ANOVA). Between the two groups which in line withthe bivariate normal distribution, the correlation analysis were compared byPearson analysis. P<0.05indicates that the difference has a statisticalsignificance.Results:1the pathologic change of renal tissue and the serum indexNormal control group kidney tissue pathological changes were not found.Chronic renal failure group, chronic renal failure group with vascularcalcification: In the areas of nephropathy, glomerulosclerosis were seen, andthe brownish crystals were present in the tubular lumen.Compared with the normal control group, the serum creatinine of Chronicrenal failure group, chronic renal failure group with vascular calcificationwere increased significantly,82.3±4.73vs32.0±2.0，P<0.05；87.6±3.18vs32.0±2.0，P<0.05；Compared with the normal control group, the serum BUNof Chronic renal failure group, chronic renal failure group with vascular calcification were increased significantly,18.1±1.60vs7.1±0.43，P<0.05；19.0±1.78vs7.1±0.43，P<0.05；There were no different between Chronicrenal failure group and chronic renal failure group with vascular calcification,87.6±3.18vs82.3±4.73，P＞0.05；19.0±1.78vs18.1±1.60，P＞0.05。2Calcification of aortaThere was no calcification in normal control geoup and chronic renalfailure group. The aorta of the chronic renal failure group with vascularcalcification were calcificated significantly. Of the calcium content, there wereon different in normal control geoup and chronic renal failure group,7.17±2.54vs6.46±2.14，P＞0.05; Compared with the chronic renal failuregroup, the aortic calcium content of the chronic renal failure group withvascular calcification were increased significantly,16.88±6.40vs6.46±2.14，P＜0.05.3Result of EVGCompared with the normal control group, the elastin of Chronic renalfailure group and chronic renal failure group with vascular calcification werestraight and thin; Compared with the Chronic renal failure group, the elastin ofchronic renal failure group with vascular calcification were less and breakage,calcification were occurred at the abruption zone.4Aortic stiffnessWe evaluated stiffness of vascular by pulse wave velocity. Comparedwith the normal control group, the PWV of Chronic renal failure group,chronic renal failure group with vascular calcification were increasedsignificantly,5.90±0.022vs2.87±0.006， P<0.05；9.032±0.041vs2.87±0.006，P<0.05；Compared with the Chronic renal failure group, thePWV of chronic renal failure group with vascular calcification was increasedsignificantly,9.032±0.041vs5.90±0.022，P<0.05.5Expression of aortic cbfa1and MMP-2Compared with the normal control group, the aortic cbfa1and MMP-2mRNA of Chronic renal failure group, chronic renal failure group withvascular calcification were increased significantly(P<0.05)；Compared with the Chronic renal failure group, the aortic cbfa1and MMP-2mRNA of thechronic renal failure group with vascular calcification were increasedsignificantly(P<0.05)；Compared with the normal control group, the aorticMMP-2of Chronic renal failure group, chronic renal failure group withvascular calcification were increased significantly(P<0.05)；Compared withthe Chronic renal failure group, the aortic MMP-2of the chronic renal failuregroup with vascular calcification were increased significantly(P<0.05).6The relationship between PWV, MMP-2, and calcium content.The change of aortic PWV and aortic calcium content were positivelyrelated（r=0.736，P=0.03）. The change of aortic PWV and expression ofMMP-2were positively related（r=0.754，P=0.02）. The expression of MMP-2mRNA and cbfa1mRNA were positively related（r=0.924，P=0.000）.Conclusions:1Vascular stiffness was decreased in chronic kidney disease rats. As theincrease of calcium content, vascular stiffness decreased.2One of the mechanisms of decreased vascular elasticity function in ratswith chronic kidney disease is elastin degradation caused by increasingexpression of MMP-2in the artery wall. |
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