膦甲酸钠对大鼠肝肾组织及相关生化病理指标的影响
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摘要
目的探讨膦甲酸钠对大鼠的肝肾组织及相关生化病理指标的影响。方法将40只SD大鼠随机分为对照组、低剂量组、中剂量组、高剂量组,每组各10只。低剂量组、中剂量组、高剂量组大鼠分别给予300 mg/kg、600 mg/kg、900 mg/kg膦甲酸钠腹腔注射,对照组大鼠给予腹腔注射等体积生理盐水。连续给药2周后,检测各组大鼠尿液肌酐、总蛋白水平,计算肌酐清除率(CCr);检测各组大鼠血清ALT、AST、AKP、尿素氮、肌酐、TG水平;分离肝脏和肾脏,测定脏器指数,显微镜观察其组织结构。结果 (1)与对照组相比,低剂量组AST及AKP水平均高(均P <0. 05),但肝脏指数差异无统计学意义(P> 0. 05),且肝脏组织结构较为完整;与对照组相比,中、高剂量组的肝脏指数以及ALT、AST、AKP、TG水平均高(均P <0. 05),且肝脏组织结构存在一定的破坏。(2)与对照组相比,不同膦甲酸钠剂量组肾脏指数、血尿素氮及肌酐、尿液总蛋白均高(均P <0. 05),而尿肌酐以及CCr值均低(均P <0. 05),肾小管和肾皮质均出现不同程度的破坏。(3)与低剂量组相比,中、高剂量组肝脏及肾脏指数、ALT、AST、AKP、TG、血尿素氮及肌酐、尿液总蛋白均高(均P <0. 05),而尿肌酐及CCr值均低(均P <0. 05),肾脏结构严重受损。结论连续使用膦甲酸钠可损害肝肾组织,对肾脏的损害更严重,而中、高剂量膦甲酸钠的作用更为明显。
Objective To explore the effect of foscarnet sodium on liver and kidney tissues and related biochemical and pathological indexes in rats. Methods Forty SD rats were randomly divided into control group,low-dose group,medium-dose group or high-dose group,with 10 rats in each group. The rats in the low-dose group,medium-dose group and high-dose group were intraperitoneally injected with 300 mg/kg,600 mg/kg and 900 mg/kg foscarnet sodium,respectively,while the rats in control group were intraperitoneally injected with equal volume of normal saline. After two weeks of continuous administration,the levels of urine creatinine and total protein were detected,and the creatinine clearance rate( CCr) was calculated; levels of serum ALT,AST,AKP,ureanitrogen,creatinine and TG were measured;and liver and kidney were removed,the organ index was measured,and the tissue structure was observed under microscope.Results( 1) Compared with the control group,the low-dose group had higher levels of AST and AKP( P < 0. 05),but its liver index was of no significant difference( P > 0. 05),and its structure of liver was relatively complete; while the medium-dose group and high-dose group had higher liver index and the levels of ALT,AST,AKP and TG( P < 0. 05),and their liver tissue structures were damaged to some extent.( 2) Compared with the control group,all the other groups of different doses had higher the kidney index,blood ureanitrogen,blood creatinine and urine total protein levels( P < 0. 05),and lower urine creatinine and CCr levels( P < 0. 05),and their renal tubules and cortexes were damaged in different degrees.( 3) Compared with the low-dose group,the medium-dose group and high-dose group had higher liver and kidney index,ALT,AST,AKP,TG,blood ureanitrogen,blood creatinine and urine total protein levels( P < 0. 05),and lower urine creatinine and CCr levels( P < 0. 05),and their kidney structures were severely damaged. Conclusion The continuous use of foscarnet sodium,especially medium-dose and high-dose foscarnet sodium,can damage liver and kidney tissues,and the damage to kidney is more serious.
Objective To explore the effect of foscarnet sodium on liver and kidney tissues and related biochemical and pathological indexes in rats. Methods Forty SD rats were randomly divided into control group,low-dose group,medium-dose group or high-dose group,with 10 rats in each group. The rats in the low-dose group,medium-dose group and high-dose group were intraperitoneally injected with 300 mg/kg,600 mg/kg and 900 mg/kg foscarnet sodium,respectively,while the rats in control group were intraperitoneally injected with equal volume of normal saline. After two weeks of continuous administration,the levels of urine creatinine and total protein were detected,and the creatinine clearance rate( CCr) was calculated; levels of serum ALT,AST,AKP,ureanitrogen,creatinine and TG were measured;and liver and kidney were removed,the organ index was measured,and the tissue structure was observed under microscope.Results( 1) Compared with the control group,the low-dose group had higher levels of AST and AKP( P < 0. 05),but its liver index was of no significant difference( P > 0. 05),and its structure of liver was relatively complete; while the medium-dose group and high-dose group had higher liver index and the levels of ALT,AST,AKP and TG( P < 0. 05),and their liver tissue structures were damaged to some extent.( 2) Compared with the control group,all the other groups of different doses had higher the kidney index,blood ureanitrogen,blood creatinine and urine total protein levels( P < 0. 05),and lower urine creatinine and CCr levels( P < 0. 05),and their renal tubules and cortexes were damaged in different degrees.( 3) Compared with the low-dose group,the medium-dose group and high-dose group had higher liver and kidney index,ALT,AST,AKP,TG,blood ureanitrogen,blood creatinine and urine total protein levels( P < 0. 05),and lower urine creatinine and CCr levels( P < 0. 05),and their kidney structures were severely damaged. Conclusion The continuous use of foscarnet sodium,especially medium-dose and high-dose foscarnet sodium,can damage liver and kidney tissues,and the damage to kidney is more serious.
引文
[1]唐伟伟.膦甲酸钠在抗病毒治疗中的临床应用现状[J].实用临床医药杂志,2015,19(17):200-202.
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[9]郝好华,宋金春,杨小青,等.五水头孢唑林钠对大鼠肝肾毒性研究[J].药学与临床研究,2015,23(1):16-20.
[10]董莉.肝肾功能检查各项指标正常范围参考值分析[J].甘肃医药,2015,34(2):129-131.
[11]魏苏宁,苏雪莹,徐国恒.肝细胞甘油三酯代谢途径异常与脂肪肝[J].中国生物化学与分子生物学报,2016,32(2):123-132.
[12]任晓蕾,黄婧,李玉珍.膦甲酸钠相关癫痫发作及肾损害[J].药物不良反应杂志,2010,12(4):239,245.
[13]李文歌.抗病毒药物的肾脏损害[J].中国医药导刊,2008,10(6):818-820,823.
[14]姜维苓,姜绪东.膦甲酸钠治疗慢性乙型病毒性肝炎的不良反应[J].医药导报,2002,21(4):251.
[15]Iwami D,Ogawa Y,Fujita H,et al. Successful treatment with foscarnet for ganciclovir-resistant cytomegalovirus infection in a kidney transplant recipient:a case report[J]. Nephrology(Carlton),2016,21(Suppl):63-66.
[2]王欣,王冰,徐明丽,何代玉,孟凡岗.膦甲酸钠注射液致急性肾功能衰竭1例[J].中国药物应用与监测,2016,13(5):324-326.
[3]夏龙,陈华.膦甲酸钠的毒性研究[J].苏州大学学报(医学版),1997,20(1):42-45,200.
[4]Shimizu R,Ohwada C,Nagao Y,et al. The successful treatment of a cord blood transplant recipient with varicella zoster virus meningitis,radiculitis and myelitis with foscarnet[J]. Intern Med,2017,56(3):353-356.
[5]胡扬,刘一,刘水,等.北京地区2008~2014年膦甲酸钠不良反应分析[J].中国药学杂志,2015,50(18):1 634-1 638.
[6]尚兰琴,魏雪涛,杨晓华,等.不同剂型膦甲酸钠针剂的肾脏毒性[J].毒理学杂志,2006,20(2):131-132.
[7]王翔.不同剂量膦甲酸钠治疗带状疱疹临床疗效观察[J].海峡药学,2010,22(5):138-139.
[8]赵伟,孙国志.不同种实验动物间用药量换算[J].畜牧兽医科技信息,2010(5):52-53.
[9]郝好华,宋金春,杨小青,等.五水头孢唑林钠对大鼠肝肾毒性研究[J].药学与临床研究,2015,23(1):16-20.
[10]董莉.肝肾功能检查各项指标正常范围参考值分析[J].甘肃医药,2015,34(2):129-131.
[11]魏苏宁,苏雪莹,徐国恒.肝细胞甘油三酯代谢途径异常与脂肪肝[J].中国生物化学与分子生物学报,2016,32(2):123-132.
[12]任晓蕾,黄婧,李玉珍.膦甲酸钠相关癫痫发作及肾损害[J].药物不良反应杂志,2010,12(4):239,245.
[13]李文歌.抗病毒药物的肾脏损害[J].中国医药导刊,2008,10(6):818-820,823.
[14]姜维苓,姜绪东.膦甲酸钠治疗慢性乙型病毒性肝炎的不良反应[J].医药导报,2002,21(4):251.
[15]Iwami D,Ogawa Y,Fujita H,et al. Successful treatment with foscarnet for ganciclovir-resistant cytomegalovirus infection in a kidney transplant recipient:a case report[J]. Nephrology(Carlton),2016,21(Suppl):63-66.