Expressions Of Adhesion Molecules And The Effects Of Scoplamine In Rats With Overtraining-induced Acute Kidney Injury

Objective: Overtraiming can induce acute kidney injury.At present, there are not effective ways to prevent and cure it atclinic. So , this is an important problem about how to explainthe disease mechanism and prevent overtraining-induced acutekidney injury. The present study developed the animal model ofovertraining-induced acute kidney injury by swimming toexhaust in rats. Through observing the expressions ofintercellular adhesion molecule-1(ICAM-1),E-cadherin,β-catenin and endothelin(ET),we analyzed if the changes ofespressions related to renal histopathologic and renal function,and observed the therapeutic effect of scopolamine, and thenexplored the useness of adhesion molecules and ET inovertraining-induced acute kidney injury. After that, we hopethat we can understand the disease mechanism deeply and offerthe theory support and test proof for prevention and cure ofovertraining-induced acute kidney injury.Methods: 42 male wistar rats weighing 200-220g wererandomly divided into 7 groups equally: the normal group(N),0h after exhausting exercise group(S0),6h after exhaustingexercise group(S6),12h after exhausting exercise group(S12),24h after exhausting exercise group(S24),6h after exhaustingexercise group treated with scopolamine(D6) ,24h afterexhausting exercise group treated with scopolamine(D24). Allrats in exhausting exercise groups swimed to exhaust anddeveloped the model of overtraining-induced acute kidneyinjury(exhausting exercise only once,not to weight). Rats intreated group were injected scopolamine (5mg/Kg, injection inperifoneal cavity). All of rats were allowed eating and drinkingfreely. The following studies were performed in every group:The amounts of blood urea nitrogen(BUN) ,serumcreatinine(Scr),creatine-kinase(CK) and urine γ–GT weremeasured; Immunohistothemical technigue was used to estimatethe expression of ICAM-1,E-cadherin,β-Catenin in renaltissue and the results were analyzed semi-quantitatively with thepathological image analysis system. Radioinmunoassay wasused to investigate the changes of ET. The renal histopathologicchanges were observed with light microscope after HEstaining.The experimental data was expressed as mean +standard deviation.The statistic significance were analyzed byspss11.0,a statistic sefeware.Result: The swimming time of exhausting exercise groupwas shorter than that of scopolamine group(P<0.01). By lightmicroscopy, the histologic changes in the kidney of exhaustingexercise group were slight: The size of glomeruli was increasedmoderately; Brush of the renal tubules loss partly and hyalinecast, granuclar cast or red cell cast could be seen in the tubulelumen occasionally. Inflammatory cells infiltrated in theinterstitial. Above all the abnormal changes could hardly befound in the group treated with scopolamine.The levels of BUNand CK in S groups were higher than N group(P<0.01 orP<0.05), and lifted up to top level at 6h after exhaustingexercise. Then the amounts of BUN and CK reduced to thenormal level at 24h after exhausting exercise. After treated withscopolamine, the levels of BUN and CK were at normal line.Above two signs were less in scopolamine group than those of Sgroup at the same time(P<0.05 or P<0.01). The levels of Scr inexhausting groups were lightly higher than normal control group.But there were no significant difference(P>0.05).The amountsof urine γ-GT increased strongly in S group following the timecontinued, especially S24 group. There was significantdifference(P<0.01)compared with that of N group. Theamounts of urine γ-GT were less in scopolamine group thanthose of S group at the same time(P<0.05 or P<0.01).Expressions of ICAM-1 were increased gradually in theglomeruli and tubules of kidneys in S group rats following thetime continued after exhausting exercise. But expressions ofE-cadherin andβ-Catenin were contrary to ICAM-1. Theirexpressions were reduced significantly in S24 group than Ngroup(P<0.01). After treated with scopolamine , those levels ofadhesion molecules were not significant difference from thoseof N group rats(P<0.05). The trends of expressions about ET inplasma were corresponded with renal tissue's: The level of EThad increased at 0h after exhausting exercise, and up to thehighest level at 6h, then reduced to the nomal level at 24h. Therewas a significant reducing in scopolamine group than S group(P<0.01).Conclusions: 1. The histopathologic changes in the kidneyof overtraining -induced acute kidney injury were slight: theglomeruli hypertrophy, the renal tubules tumefied, renal tubulebrush loss partly and the less tubule cast was found. 2.Expressions of ICAM-1 were increased strongly in the renaltissue followed the time continued. The expressions ofE-cadherin and β-Catenin reduced sighificantly at the sametime. These changes of adhesion molecules are the importantpathogenesis of overtraining-induced acute kidney injury. 3. Theexpressions of ET in plasma and renal tissue were increased atbeginning and reduced at 6h after exhausting exercise. Thistrend was corresponded with the changes of renal function. Thechanges of ET play an important role in the happening,developing and instauration of overtraining-induced acutekidney injury. 4. Scopolamine can alleviate overtraining-induced acute kidney injury by turning down the expression ofICAM-1, turning up the expressions of E-cadherin and β-Catenin, protecting the nomal adheren junction, maintainingthe stability of ET and improving the abnormal blood flowing...