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期刊信息:
《药学服务与研究》2017年, 第17卷, 第6期, 第449-452页
标题:
阿德福韦酯长期应用引起大鼠肾损伤的评价
DOI:
10.5428/pcar20170615
作者:
1. 徐爱静(第二军医大学长海医院感染科 上海 200433 [email protected])
2. 孔德亮(第二军医大学长海医院感染科 上海 200433 )
3. 李成忠(第二军医大学长海医院感染科 上海 200433 )
4. 梁雪松(第二军医大学长海医院感染科 上海 200433 [email protected])
摘要:
摘要  目的:观察大鼠使用阿德福韦酯(adefovir dipivoxil,ADV)8周对肾脏的影响。方法:采用灌胃法制作大鼠ADV肾病模型。将30只大鼠分为5组:空白对照(A)组,生理盐水(B)组,ADV给药8周停药0周(C1)组、ADV给药8周停药4周(C2)组、ADV给药8周停药8周(C3)组,每组6只。生理盐水组和ADV给药组大鼠灌胃给予生理盐水和ADV 1 mg/kg,每天给药一次,连续给药8周,灌胃容积为10 ml/kg。最后一次灌胃后24 h,收集A、B、C1组大鼠的外周血和尿液;,于停药4周和8周后分别收集C2和C3组大鼠的外周血和尿液,检测血清肌酐(Scr)、血清磷、血清钙,血β2-微球蛋白(β2-MG)和尿β2-MG水平,尿β-N-乙酰氨基葡萄糖苷酶(NAG)的活性。并取大鼠肾脏,观察组织病理学变化。结果:A、B、C1组大鼠血清Scr、血清磷、血清钙、血β2-MG、尿β2-MG和尿NAG的差别无显著意义(P>0.05);C1、C2、C3组大鼠血清Scr、血清磷、血清钙、血β2-MG和尿β2-MG差别无显著意义(P>0.05),C3组大鼠尿NAG活性显著高于C2组(P<0.05)。C1组大鼠肾小管上皮细胞呈轻度至中度肿胀变性和脱颗粒,个别肾小管腔含有红细胞管型,肾小球结构完整,无明显肾小管坏死或萎缩,肾间质可见明显纤维化及炎性细胞浸润。停药4周后(C2组)肾小管上皮细胞损伤与停药0周(C1组)相比有明显改善,C3组大鼠肾小管损伤与C2组比较有好转,但亦未完全恢复。结论:ADV 1 mg/(kg·d)给药8周可引起大鼠肾小管损伤,在停药8周后没有完全恢复。临床常规检测指标,如血肌酐、β2-MG等,无法完全反映长期使用ADV引起的早期肾损伤。
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若需在您的论文中引用此文,请按以下格式著录参考文献:
中文著录格式 徐爱静,孔德亮,李成忠,梁雪松. 阿德福韦酯长期应用引起大鼠肾损伤的评价[J]. 药学服务与研究. 2017; 17(6): 449-452.
英文著录格式 XU AiJing,KONG DeLiang,LI ChengZhong,LIANG XueSong. Evaluation of renal injury induced by long-term use of adefovir dipivoxil in rats[J]. Pharmaceutical Care and Research / yao xue fu wu yu yan jiu. 2017; 17(6): 449-452.
参考文献:
1. 中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2015年版)[J].中华实验和临床感染病杂志(电子版),2015,9(5):570-589.
2. Hadziyannis S J,Tassopoulos N C,Heathcote E J,et al.Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years[J].Gastroenterology,2006,131(6):1743-1751.
3. Ha N B,Ha N B,Garcia R T,et al.Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil[J].Hepatology,2009,50(3):727-734.
4. Mederacke I,Yurdaydin C,Groβhennig A,et al.Renal function during treatment with adefovir plus peg interferon α-2a vs either drug alone in hepatitis B/D co-infection[J].J Vir Hepat,2012,19(6):387-395.
5. Khungar V,Han S-H.A systematic review of side effects of nucleoside and nucleotide drugs used for the treatment of chronic hepatitis B[J].Curr Hepat Rep,2010,9(2):75-90.
6. 曾彩虹,黄倩,范芸,等.阿德福韦酯相关肾脏损害[J].肾脏病与透析肾移植杂志,2013,22(1):26-31.
7. Wong C C,Botting N P,Orfila C,et al.Flavonoid conjugates interact with organic anion transporters (OATs) and attenuate cytotoxicity of adefovir mediated by organic anion transporter 1 (OAT1/SLC22A6)[J].Biochem Pharmacol,2011,81(7):942-949.
8. Mandíková J,Volková M,Pávek P,et al.Interactions with selected drug renal transporters and transporter-mediated cytotoxicity in antiviral agents from the group of acyclic nucleoside phosphonates[J].Toxicology,2013,311(3):135-146.
9. Tanji N,Tanji K,Kambham N,et al.Adefovir nephrotoxicity: possible role of mitochondrial DNA depletion[J].Hum Pathol,2001,32(7):734-740.
10. Kim Y J,Cho H C,Sinn D H,et al.Frequency and risk factors of renal impairment during long-term adefovir dipivoxil treatment in chronic hepatitis B patients[J].J Gastroenterol Hepatol,2012,27(2):306-312.
11. 刘俊兰,凌毅生,关天俊.长期应用阿德福韦酯慢性乙型肝炎患者肾脏损害的临床研究[J].中华全科医师杂志,2014,13(2):142-144.
12. Donadio C.Serum and urinary markers of early impairment of GFR in chronic kidney disease patients: diagnostic accuracy of urinary β-trace protein[J].Am J Physiol Renal Physiol,2010,299(6):F1407-F1423.
13. LUO Qing,DENG Yong,CHENG FeiFei,et al.Relationship between nephrotoxicity and long-term adefovir dipivoxil therapy for chronic hepatitis B:a meta-analysis[J].Medicine,2016,95(50):e5578.
14. JIA HongYu,DING Feng,CHEN JianYang,et al.Early kidney injury during long-term adefovir dipivoxil therapy for chronic hepatitis B[J].World J Gastroenterol,2015,21(12):3657-3662.