地塞米松预处理小鼠肾缺血再灌注损伤研究
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摘要
目的:验证地塞米松预处理是否可减轻肾缺血再灌注损伤,并探讨其使用剂量与肾缺血再灌注损伤减轻程度的相关性。方法:30只健康雄性C57BL/6小鼠随机分成5组,假手术组、肾缺血再灌注组、地塞米松2mg/kg组、4mg/kg组、6mg/kg组,每组6只。假手术组及缺血再灌注组,术前30min给予生理盐水腹腔注射。地塞米松预处理组小鼠,术前30min分别予以2mg/kg、4mg/kg及6mg/kg剂量的地塞米松腹腔注射。不同剂量地塞米松预处理小鼠及缺血再灌注组小鼠开腹后用血管夹夹闭右侧肾蒂,生理盐水浸湿纱布覆盖切口置于32℃温箱45min,然后松开血管夹,恢复肾脏血流灌注,去除左侧肾脏,缝合腹部,术毕放回动物房。松开血管夹后24h处死小鼠,收集血清和肾脏标本进行相关检测。结果:地塞米松预处理组小鼠的尿素氮、肌酐水平均显著低于缺血再灌注组小鼠,且肾脏病理可见其肾小管上皮细胞肿胀、空泡变性程度及炎性细胞浸润程度也轻于缺血再灌注组。2mg/kg组小鼠的尿素氮、肌酐水平显著高于4mg/kg组与6mg/kg组,差异有统计学意义,而4mg/kg组与6mg/kg组间差异无统计学意义。肾脏病理可见2mg/kg组小鼠的肾小管上皮细胞肿胀、空泡变性程度及炎性细胞浸润程度较4mg/kg组与6mg/kg组重,差异有统计学意义,但4mg/kg组与6mg/kg组间差异无统计学意义。结论:地塞米松预处理可以减轻肾缺血再灌注损伤,但其减轻程度与其使用剂量不完全呈正相关。
Objective:To verify whether dexamethasone pretreatment can alleviate renal ischemia-reperfusion injury, and to investigate the correlation between the dosage of dexamethasone pretreatment and the degree of renal ischemia-reperfusion injury.Methods:Thirty C57 BL/6 male mice were randomly divided into five groups: sham-operated group(Sham),renal ischemia-reperfusion group(IRI),dexamethasone 2 mg/kg group(Dex 2 mg/kg),4 mg/kg group(Dex 4 mg/kg) and 6 mg/kg group(Dex 6 mg/kg),with 6 mice in each group.The mice in dexamethasone pretreatment group were given with 2 mg/kg, 4 mg/kg and 6 mg/kg doses of dexamethasone at 30 minutes before operation, and the mice in sham group and ischemia-reperfusion group were given with saline of equal volume at 30 min before operation.The mice in Dex group and IRI group were treated with blood vessel clamp to close the right renal pedicle after laparotomy. Normal saline soaked gauze covered the incision and placed in a 32 degrees centigrade temperature box for 45 minutes.Then the blood vessel clamp was loosened to restore renal blood flow perfusion, the left kidney was removed, the abdomen was sutured and put back into the animal room after operation.The mice were sacrificed 24 hours after the clamp was loosened. Serum and kidney samples were collected for related detection.Results:The levels of urea nitrogen and creatinine in mice pretreated with dexamethasone were significantly lower than those in ischemia-reperfusion group, and renal pathology showed that the degree of tubular swelling and necrosis and inflammatory cell infiltration in mice pretreated with dexamethasone were also less than those in ischemia-reperfusion group. The levels of urea nitrogen and creatinine in 2 mg/kg group were significantly higher than those in 4 mg/kg group and 6 mg/kg group, but there was no significant difference between 4 mg/kg group and 6 mg/kg group. Kidney pathology showed that the degree of tubular swelling and necrosis and inflammatory cell infiltration in 2 mg/kg group were significantly higher than those in 4 mg/kg group and 6 mg/kg group, but there was no significant difference between 4 mg/kg group and 6 mg/kg group.Conclusion:Dexamethason pretreatment can alleviate renal ischemia-reperfusion injury, but the degree of reduction is not entirely positively correlated with its dosage.
Objective:To verify whether dexamethasone pretreatment can alleviate renal ischemia-reperfusion injury, and to investigate the correlation between the dosage of dexamethasone pretreatment and the degree of renal ischemia-reperfusion injury.Methods:Thirty C57 BL/6 male mice were randomly divided into five groups: sham-operated group(Sham),renal ischemia-reperfusion group(IRI),dexamethasone 2 mg/kg group(Dex 2 mg/kg),4 mg/kg group(Dex 4 mg/kg) and 6 mg/kg group(Dex 6 mg/kg),with 6 mice in each group.The mice in dexamethasone pretreatment group were given with 2 mg/kg, 4 mg/kg and 6 mg/kg doses of dexamethasone at 30 minutes before operation, and the mice in sham group and ischemia-reperfusion group were given with saline of equal volume at 30 min before operation.The mice in Dex group and IRI group were treated with blood vessel clamp to close the right renal pedicle after laparotomy. Normal saline soaked gauze covered the incision and placed in a 32 degrees centigrade temperature box for 45 minutes.Then the blood vessel clamp was loosened to restore renal blood flow perfusion, the left kidney was removed, the abdomen was sutured and put back into the animal room after operation.The mice were sacrificed 24 hours after the clamp was loosened. Serum and kidney samples were collected for related detection.Results:The levels of urea nitrogen and creatinine in mice pretreated with dexamethasone were significantly lower than those in ischemia-reperfusion group, and renal pathology showed that the degree of tubular swelling and necrosis and inflammatory cell infiltration in mice pretreated with dexamethasone were also less than those in ischemia-reperfusion group. The levels of urea nitrogen and creatinine in 2 mg/kg group were significantly higher than those in 4 mg/kg group and 6 mg/kg group, but there was no significant difference between 4 mg/kg group and 6 mg/kg group. Kidney pathology showed that the degree of tubular swelling and necrosis and inflammatory cell infiltration in 2 mg/kg group were significantly higher than those in 4 mg/kg group and 6 mg/kg group, but there was no significant difference between 4 mg/kg group and 6 mg/kg group.Conclusion:Dexamethason pretreatment can alleviate renal ischemia-reperfusion injury, but the degree of reduction is not entirely positively correlated with its dosage.
引文
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[3] 李德新,李敬东.地塞米松在肝脏缺血再灌注损伤的保护作用及 NO、iNOS 研究进展[J].中华肝脏病杂志,2010,18(11):875-877.
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[6] Bonventre JV,Weinberg JM.Recent advances in the pathophysiology of ischemic acute renal failure.[J] JASN,2003,14(8):2199-2210.
[7] Lu CY,Hartono J,Senitko M,et al.The inflammatory response to ischemic acute kidney injury:a result of the 'right stuff in the 'wrong place' [J].Current opinion in nephrology and hypertension,2007,16(2):83-89.
[8] 孙颖,张炯,吕倩,等.地塞米松预处理减轻肾缺血再灌注损伤[J].临床肾脏病杂志,2014,14(3):173-176.
[9] 江潮.地塞米松减轻肾脏缺血再灌注损伤的作用和机制研究[D].武汉:华中科技大学同济医学院,2014.
[10] 袁伟,杨娟,陈美雪,等.地塞米松预处理减轻小肠—缺血再灌注损伤[J].医药导报,2015,34(5):574-577.
[11] Sanjeev Kumar,David A.Allen,Julius E.Kieswich,et al.Dexamethasone Ameliorates Renal Ischemia Reperfusion Injury[J].J Am Soc Nephrol,2009,20:2412-2425.
[12] Becker DE.Basic and clinical pharmacology of glucocorticosteroids[J].Anesthesia progress,2013,60(1):25-31.
[2] 庄梅,方颖,吴立荣,等.地塞米松对大鼠心肌缺血再灌注后细胞凋亡及金属硫蛋白表达的影响[J].中华老年心脑血管病杂志,2008,10(7):533-546.
[3] 李德新,李敬东.地塞米松在肝脏缺血再灌注损伤的保护作用及 NO、iNOS 研究进展[J].中华肝脏病杂志,2010,18(11):875-877.
[4] Kumar S,Allen DA,Kieswich JE,et al.Dexamethasone ameliorates renal ischemia-reperfusion injury[J].JASN,2009,20(11):2412-2425.
[5] Gu J,Sun P,Zhao H,et al.Dexmedetomidine provides renoprotection against ischemia-reperfiision injury in mice[J].Critical Care,2011,15(3):R153.
[6] Bonventre JV,Weinberg JM.Recent advances in the pathophysiology of ischemic acute renal failure.[J] JASN,2003,14(8):2199-2210.
[7] Lu CY,Hartono J,Senitko M,et al.The inflammatory response to ischemic acute kidney injury:a result of the 'right stuff in the 'wrong place' [J].Current opinion in nephrology and hypertension,2007,16(2):83-89.
[8] 孙颖,张炯,吕倩,等.地塞米松预处理减轻肾缺血再灌注损伤[J].临床肾脏病杂志,2014,14(3):173-176.
[9] 江潮.地塞米松减轻肾脏缺血再灌注损伤的作用和机制研究[D].武汉:华中科技大学同济医学院,2014.
[10] 袁伟,杨娟,陈美雪,等.地塞米松预处理减轻小肠—缺血再灌注损伤[J].医药导报,2015,34(5):574-577.
[11] Sanjeev Kumar,David A.Allen,Julius E.Kieswich,et al.Dexamethasone Ameliorates Renal Ischemia Reperfusion Injury[J].J Am Soc Nephrol,2009,20:2412-2425.
[12] Becker DE.Basic and clinical pharmacology of glucocorticosteroids[J].Anesthesia progress,2013,60(1):25-31.