| Objective：To analysis the relationship of the levels of serum asymmetricdimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and theindex of traditional evaluation of renal function and the degree of renalpathology by a rat model of chronic renal failure.Method：84male Sprague-Dawley rats were randomly divided into twogroups: sham operation group (SHAM, n＝42) and5/6nephrectomy group(SNX, n＝42). Model group was produced5/6nephrectomy to form chronicrenal failure model, the entire modeling process in two phases surgery, shamgroup over the same period for surgery, the two operations are only separatedfatty renal capsule and renal pedicle, stripping the left and right kidney fascia,without nephrectomy. As the beginning of the observation period to the end ofthe second stage surgery, before the day of4,6,8,10,12,14weekend, randomlyselected6rats from sham group and model group separately, collected24-hour urine for the determination of24-hour urinary protein excretion, urinevolume and urine creatinine, each weekend obtained blood through abdominalaortic puncture for serum creatinine, blood urea nitrogen, and calculated thecreatinine clearance, and using high-performance liquid chromatography(HPLC) to determinate the levels of ADMA and SDMA. Took out leftkidney of sham group, and left remnant kidney of model group for PAS andMasson staining, observed the pathological changes in different periods, andevaluated the degree of pathological damage by glomerulosclerosis index(GSI), tubulointerstitial score (TIS). Observe the changes of each index withtime, analysis the correlation between the levels of dimethyl arginine andtraditional marker of renal function, the degree of pathological injury. Result：1General condition:The performance of the sham group rats were alert, responsive, normalbehavior, dense neat shiny furred, normal diet, and without bloody secretionsaround the urethra, the weight increased gradually. Model group rats wassluggish and slow activity, even arched back and the fur was curled andwithered, appetite decreased, some of the animals had bloody secretionsaround urethra, the color and quality of stool was normal, some rats’ stooloutput was reduced, the weight increased slowly. With prolonged observationperiod, compared with the sham group, rats’ ear, nose, dorsal, tail skin wasslightly pale. Some of the rats had small to moderate amount of ascites.2Routine biochemical detection of each period:24-hour urinary protein excretion: Compared with the sham group, therewere significant differences in8,10,12,14weeks in model group (P＜0.01).Serum creatinine: Compared with the sham group, there were significantdifferences in each periods in model group, including differences (P＜0.05) in4weeks, the rest of the period was significantly different (P＜0.01). BUN:Compared with the sham group, there were significant differences in eachperiods in model group (P＜0.01). Creatinine clearance rate: Compared withthe sham group, there were significant differences in6,8,10,12,14weeks inmodel group (P＜0.01).3Dimethyl arginine detection of each period:Serum ADMA: Compared with the sham group, there were significantdifferences in4,6,10,12,14weeks in model group, including differences (P＜0.05) in10weeks, the rest of the period was significantly different (P＜0.01). Serum SDMA: Compared with the sham group, there were differencesin12,14weeks in model group (P＜0.05).4Renal pathological damage assessment:GSI: Compared with the sham group, there were differences in4,8,10,12,14weeks in model group, including differences (P＜0.05) in4weeks, therest of the period was significantly different (P＜0.01). TIS: Compared withthe sham group, there were differences in6,8,10,12,14weeks in model group, including differences (P＜0.05) in6weeks, the rest of the period wassignificantly different (P＜0.01).5The trends of all biochemical indices:4to6weeks after surgery, serum creatinine, blood urea nitrogenincreased, the rate creatinine clearance declined, for the compensatory role ofresidual renal units, in6to8weeks, there was a certain degree of recovery, therenal indicators are suggestive decreased after8weeks.4to6weeks aftersurgery, serum ADMA, SDMA raised, there was a certain degree of recoveryin6to8weeks, and suggestive raise after8weeks. Defined8weeks as astarting point of the observation of chronic renal failure.6Correlation analysis:①Correlation analysis of dimethyl arginine and the traditional kidneyfunction indicators:There were positive correlations between ADMA and Scr (r＝0.587, P＜0.01), BUN (r＝0.617, P＜0.01), and there was a negative correlationbetween ADMA and Ccr (r＝﹣0.479, P＜0.01). There were positivecorrelations between SDMA and Scr (r＝0.420, P＜0.01), BUN (r＝0.442, P＜0.01), and there was a negative correlation between SDMA and Ccr (r＝﹣0.427, P＜0.01).②Correlation analysis of dimethyl arginine and pathological damageindices:There were positive correlations between ADMA and GSI (r＝0.694, P＜0.01), TIS (r＝0.650, P＜0.01). and there were positive correlations betweenSDMA and GSI (r＝0.495, P＜0.01), TIS (r＝0.485, P＜0.01).Conclusion：1The experimental application built from5/6nephrectomy rat model ofchronic renal failure, the model has a strong clinical similarity, reliability.2Serum ADMA, SDMA levels were increased with the progress ofchronic renal failure.3There were correlations between ADMA, SDMA and indices oftraditional renal function, and ADMA was better than SDMA, suggesting dimethyl arginine may be used as indicators of the evaluation of renalfunction.4There were correlations between ADMA, SDMA and indices ofpathological damage evaluation, and ADMA was better than SDMA, whichprompted dimethylarginine as indicators of the degree of renal pathologicaldamage, but did not reflect the specificity of the glomerular or tubuleinterstitial injury. |
PDF Full Text Request