| Objective In this study we observed and researched the protective effects of LC on theCarboplain-induced kidney damage in rats, and attempted to provid some significantexperimental bases for the prevention of nephrotoxicity in Carboplain-treated patientswith cancer. And confirmed that Kim-1is the first injury biomarker of kidney toxicityqualified and is expected to significantly improve kidney safety monitoring.Methods65male adult Sprague-Dawley rats were randomly divided into three groups,normol control (CN)5rats, Carboplain (CP)30rats, Carboplain+Acetyl L-carnitine(LC+CP)30rats. Control group: Every rats injected intraperitoneally with saline5ml/kgin4days and were sacrificed on fifth day; Carboplain model group::Every rats injectedintraperitoneally with saline5ml/kg in4days,on the fifth day every one injectedintraperitoneally with Carboplain of7mg/kg. In the first6h,12h,24h,48h,3d,5d randomsample of five rats put to death; Acetyl L-carnitine group: Every rats injectedintraperitoneally with Acetyl L-carnitine500mg/kg in4days, on the fifth day every oneinjected intraperitoneally with Carboplain of7mg/kg. In the first6h,12h,24h,48h,3d,5d random sample of five rats put to death. When every rat were killed puncture bladderfor urinary to measure kidney injury molecule-1(Kim-1)，and to collection bloodmeasurement of serum creatinine(Scr) and kidney injury molecule-1(Kim-1). The extentof the kidney was evaluated by measuring kidney injury molecule-1(Kim-1) in thekidney tissue homogenate. And RNA was determined in the kidney to do real-timequantitative PCR for kidney injury molecule-1(Kim-1) expression.The renal injury wasalso assessed by hematoxylin and eosin staining.Results With normal control group of rats, Carboplain model group scr levels wassignificantly higher (P<0.05), which slowdown in the speed increased at the third day;Carboplain model rats urine and kidney tissue of The kidney injury molecule-1levelswas significantly increased at6th hour than normal control group(P<0.05), which isearlier than the morphological changes of renal tubular epithelial cells and renal tubularepithelial cell injury increase the concentration increased gradually with the extension ofthe course; Real-time quantitative PCR showed that KIM-1gene expression significantlyupregulateder than the normal group and remained at a higher level of expression in renal tubular cells to self-repair, which may promote the repair of the renal tubular cells;HE staining signify the renal injury; with Carboplain model group of rats, whichreaches to worst point at the third day and began to self-healing at fifth day; Acetyl L-carnitine group scr levels was significantly lower (P <0.05), HE staining signify the renalinjury reduce, urine and kidney tissue of renal injury molecule-1were significantly lower(P<0.05), Real-time PCR showed that KIM-1gene expression also significantly downcompared with the same time period of Carboplain model group. Kidney injurymolecule-1determination of serum analysis showed no significant difference among thegroups (P>0.05).Conclusions1. Carboplain can cause acute renal tubular injury, and the degree ofkidney injury related to the process of severe acute pancreatitis;2. The third day inCarboplain-induced acute kidney injury is important turning point, which the damagereached a peak;3. In Carboplain-induced acute kidney injury, at sixth hour the kidneyinjury molecule-1began highly expressed, which earlier than the morbid histologicalinjury;4. The kidney injury molecule-1in urine and renal tissue is highly expressedthrough the whole process and positively correlated with the degree of renal injury;5.Kidney injury molecule-1in blood was no significant increase may be related to lessrelevant from the absorption;6. Kidney injury molecule-1can be carried out in earlydiagnosis for its good sensitivity and specificity, and it is superior to traditional creatininedetermination;7. Acetyl L-carnitine protected the renal tissue from nephrotoxicityinduced by Carboplain. |
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