| Background:The kidney injury mechanism after long term ketamine abuse has not been fully enunciated.This research established ketamine-inducted kidney damage model of SD rats, to observe the behaviors and weight changes of rats. We also determined the content of malonyldialdehyde (MDA), activity of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)in renal tissue, and observed the pathological variation by HE staining. The TUNEL apoptosis was used to analysis pathological changes in morphology of kidneys. The protections of melatonin (MT) to ketamine-inducted kidney damage rats were also observed.Objective:To elucidate possible mechanism and the therapeutic effect of metatonin on renal injury induced by ketamine.Methods:Thirty adult healthy male Sprague Dawley (SD) rats were randomly divided into three groups:(1)Control group:10 rats;(2)ketamine group:10 rats; (3)MT group:10 rats. The rats of Control group,Ketamine group,MT group were given intraperitoneal injection of 0.9% saline,100mg/Kg ketamine,100mg/Kg ketamine+10mg/Kg metatonin daily. Respectively, the body weight was measured once a week to adjust the dose of drug. After 12 weeks the rats were killed,5 ml blood of abdominal aorta were collected for renal function tests. Kidney tissue SOD, GSH-Px activity and MDA concentration were measured. Part of the renal tissue was stained with hematoxylin-eosin, masson, TUNEL apoptosis for pathological observation.Results:1.Behavioral changes and weight changes of ratsAfter injection of saline in control group, the behavioral activities of rats were normal. Rats in ketamine group and MT group after injection of drugs,having slight agitation and increased activities,came into situation of depth anesthesia within 1minutes. From the started second to twelve week,as times went on the average weight of control group highly compered with ketamine group and MT group. Interestingly, the body weight increasing trend of MT group was higher than ketamine group (P<0.05)2.Renal function results of rats.Scr, BUN of rats showed no significant differences among the groups relatively. Although each group of Scr,BUN means were indifference, there were still (14/20) Scr and (12/20) BUN in ketamine group and MT group higher than control group mean level,which suggested that ketamine and its metabolites might have bad effects on rat kidney filtration.3. Kidney homogenate measurementThe levels of MDA in each groups had significant differences (P< 0.001).The levels of MDA in ketamine group were higher than control group (P<0.001). And compared with K group,MT was obviously inhibited the rised level of MDA trends in the rat kidney tissue P< 0.001)The activity of SOD in each groups had significant differences (P< 0.001).The activity of SOD in ketamine group were significant lower than control group (P< 0.001).And compared with K group,MT was obviously improved the level of SOD in the rat kidney homogenate in MT group (P< 0.05)The activity of GSH-Px in each groups had significant differences (P< 0.001).The activity of GSH-Px in ketamine group were significant lower than control group (P< 0.001).And compared with K group,MT was obviously improved the level of GSH-Px in the rat kidney homogenate in MT group (P <0.05)4.Rats kidneys HE stainingThe morphology of renal and tubular in control group were normal,no edema distortion and necrosis. In ketamine group,there were many inflammatory cell infiltration surrounding renal interstitium and glomeruli. A lot of tubular edema,hydropic degeneration,widespread and severe vacuolar changes, renal balls shrink,even glomerilar atresia could be seem and renal interstitial fibrous cord formed too. However,in MT group,the negative damage were relieved significantly.5.Rats kidneys Masson stainingKetamine group and MT group showed renal interstitial collagen staining deeper than control group. A quantitative analysis of average renal interstitial collagen area. Average renal interstitial collagen area mean of control group,Ketamine group,MT group were (8.97%±0.02), (41.49%±0.03), (28.54%±0.04),respectively. Between Ketamine group and MT group,there were difference (P<0.001),which indicated that MT played a negative role to relieve the damage of ketamine.6.Rats kidneys TUNEL apoptosisIn control group, there were occasional apoptotic cells,which might be false positive results or normal kidney cells apoptotic. But in ketamine group and MT group showed a significant apoteosis increasingly. The semi-quantitative analysis found that the mean renal tubular positive cells per high-power microscope of control group,ketamine group,MT group were(64.56±17.90),(171.76±14.67),(149.92±27.87),respectively.There were significant difference among the there groups(P< 0.001).Between Ketamine group and MT group,there were difference (P<0.05),which indicated that MT had played a negative role to relieve the damage of ketamine.Conclutions:1.Long term ketamine intraperitoneal injection can induce renal injury and was a reliable method of making a model of chronic renal injury;2. Ketamine can results in higher levels of MDA of rats kidney tissue and lower activity of SOD,GSH-Px,which indicated that oxidative insult may be one of the mechanisms of Ketamine-induced renal injury. MT treatment decreased significantly the content of MDA of rats kidney tissue and increased the activity of SOD and GSH-Px to alleviate the renal injury;3.Ketamine induced inflammation cells infiltration and increased renal tubule cell apoptosis in kidney tissue of rats, while MT can decrease the level of renal tubule cell apoptosis, which was possibly due to it can enhance anti-oxidation ability in rats. |
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