白芍总苷对庆大霉素所致急性肾功能衰竭保护作用的研究
|
摘要
目的研究白芍总苷(total glucosides of paeony,TGP)对庆大霉素(gentamicin,GM)所致大鼠急性肾功能衰竭(acute renal failure,ARF)的保护作用并初探其可能的作用机制。方法 120只实验用Wistar大鼠通过腹腔注射GM制备ARF大鼠模型,随机分为模型对照组、肾炎康复片800 mg/(kg·d)组、TGP低[75mg/(kg·d)]、中[150 mg/(kg·d)]、高[300 mg/(kg·d)]剂量组,各20只;并取20只同龄Wistar大鼠设为正常对照组;各组均连续14 d给药(1次/d),正常对照组同步给予生理盐水。收集并测量24 h尿量,测定24 h尿蛋白量(Pro)和N-乙酰-β-氨基葡萄糖苷酶(NAG酶)活性;测定肾功能相关指标;计算肾脏指数,HE染色法观察肾脏组织病变并进行损伤评分、电子显微镜观察肾脏组织细胞超微结构变化,测定肾脏组织氧化应激监测指标,酶联免疫吸附法(ELISA)检测肾脏组织巨噬细胞炎症蛋白-2(MIP-2)、单核细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子-α(TNF-α)含量。结果与模型对照组比较,TGP中、高剂量组GM所致ARF大鼠24 h尿量和Pro减少、尿NAG酶活性降低(P<0.05或P<0.01);肾功能指标明显改善(血清BUN、SCr含量均显著降低,P<0.05或P<0.01),肾脏质量显著降低、肾脏指数显著减小(P<0.05或P<0.01),肾脏组织结构病变及细胞超微结构改变均明显改善,损伤评分显著降低(P<0.05或P<0.01),SOD、CAT活性升高且MDA含量降低(P<0.05或P<0.01),MIP-2、MCP-1、TNF-α含量降低(P<0.05或P<0.01)。结论TGP对GM所致ARF大鼠肾组织损伤具有一定的保护作用,作用机制可能与其改善肾功能、抗氧化、抑制炎症有关。
Objective To investigate the protective effect of total glucosides of paeony(TGP) on acute renal failure(ARF) induced by gentamicin(GM) and its possible mechanism.Methods One hundred experimental Wistar rats were used to made ARF rat model by intraperitoneal injection of GM.The rat models were randomly divided into model control group,Nephritisehabilitation tablets group(800 mg/(kg·d)),TGP low-dose group(75 mg/(kg·d)),TGPmedium-dose group(150 mg/(kg·d)),TGP high-dosegroup(300 mg/(kg·d)),20 rats in each group.Twenty Wistar rats of the same age were selected as normal control group.Each group was given saline for 14 d(once a day),and the normal control group was given saline at the same time.24 h urine volume was collected and measured,24 h urinary protein content(Pro) and NAG activity were measured,renal function related indicators were measured,renal index was calculated,renal pathological changes were observed.HE staining was used to observe the pathological changes of kidney tissues,and to evaluate injury score.Ultrastructural changes of renal tissue cells were observed by electron microscopy,oxidative stress monitoring indicators were determined,and the contents of MIP-2,MCP-1 and TNF-αwere detected by ELISA.Results Compared with model control group,the 24 h urine volume,Pro and NAG activity of ARF rats induced by GM in TGP medium-dose and high-dose groups significantly decreased and the activity of NAG were significantly decreased(P<0.05,P<0.01).The renal function indicators significant improved(thecontent of BUN,SCr significantly decreased(P<0.05,P<0.01).The quality of kidney significantly decreased,the index of kidney significantly decreased(P<0.05,P<0.01).The pathological changes of renal tissue and ultrastructure significantly improved,the injury scores significantly decreased(P<0.05,P<0.01).The activities of SOD and CAT increased and the content of MDA decreased(P<0.05,P<0.01),while the contents of MIP-2,MCP-1 and TNF-a decreased(P<0.05,P<0.01).renal weight,renal index were significantly decreased(P<0.05,P<0.01).Both of renal tissue structure lesions and cell ultrastructural changes were significantly improved,the damage score were significantly reduced(P<0.05 or P<0.01); the activity of SOD,CAT in renal tissue were significantly increased and the level of MDA were decreased(P<0.05 or P<0.01); the content of MIP-2,MCP-1,TNF-α were significantly decreased(P<0.05 or P<0.01).Conclusion TGP has a protective effect on renal tissue injury induced by GM in ARF rats.Its mechanism may be related to its improvement of renal function,antioxidation and inhibition of inflammation.
Objective To investigate the protective effect of total glucosides of paeony(TGP) on acute renal failure(ARF) induced by gentamicin(GM) and its possible mechanism.Methods One hundred experimental Wistar rats were used to made ARF rat model by intraperitoneal injection of GM.The rat models were randomly divided into model control group,Nephritisehabilitation tablets group(800 mg/(kg·d)),TGP low-dose group(75 mg/(kg·d)),TGPmedium-dose group(150 mg/(kg·d)),TGP high-dosegroup(300 mg/(kg·d)),20 rats in each group.Twenty Wistar rats of the same age were selected as normal control group.Each group was given saline for 14 d(once a day),and the normal control group was given saline at the same time.24 h urine volume was collected and measured,24 h urinary protein content(Pro) and NAG activity were measured,renal function related indicators were measured,renal index was calculated,renal pathological changes were observed.HE staining was used to observe the pathological changes of kidney tissues,and to evaluate injury score.Ultrastructural changes of renal tissue cells were observed by electron microscopy,oxidative stress monitoring indicators were determined,and the contents of MIP-2,MCP-1 and TNF-αwere detected by ELISA.Results Compared with model control group,the 24 h urine volume,Pro and NAG activity of ARF rats induced by GM in TGP medium-dose and high-dose groups significantly decreased and the activity of NAG were significantly decreased(P<0.05,P<0.01).The renal function indicators significant improved(thecontent of BUN,SCr significantly decreased(P<0.05,P<0.01).The quality of kidney significantly decreased,the index of kidney significantly decreased(P<0.05,P<0.01).The pathological changes of renal tissue and ultrastructure significantly improved,the injury scores significantly decreased(P<0.05,P<0.01).The activities of SOD and CAT increased and the content of MDA decreased(P<0.05,P<0.01),while the contents of MIP-2,MCP-1 and TNF-a decreased(P<0.05,P<0.01).renal weight,renal index were significantly decreased(P<0.05,P<0.01).Both of renal tissue structure lesions and cell ultrastructural changes were significantly improved,the damage score were significantly reduced(P<0.05 or P<0.01); the activity of SOD,CAT in renal tissue were significantly increased and the level of MDA were decreased(P<0.05 or P<0.01); the content of MIP-2,MCP-1,TNF-α were significantly decreased(P<0.05 or P<0.01).Conclusion TGP has a protective effect on renal tissue injury induced by GM in ARF rats.Its mechanism may be related to its improvement of renal function,antioxidation and inhibition of inflammation.
引文
[1]Srisung W,Teerakanok J,Tantrachoti P,et al.Surgical prophylaxis with gentamicin and acute kidney injury:a systematic review and meta-analysis[J].Ann Transl Med,2017,5(5):100-112
[2]Teslariu O,Pasca AS,Mititelu-Tartau L,et al.The protective effects of zinc in experimental gentamicin induced acute renal failure in rats[J].J Physiol Pharmacol,2016,67(5):751-757
[3]El-Ashker M,Abdelhamid F,Risha E,et al.Vitamin C ameliorates gentamicin-induced acute kidney injury in equines:an experimental study[J].J Equine Vet Sci,2015,35(3):238-243
[4]李明,刘勇强,敖华,等.葛根素减轻庆大霉素诱导的大鼠急性肾损伤[J].中国实验方剂学杂志,2017,23(17):177-182
[5]王晓纲.白芍总苷对动脉粥样硬化大鼠氧化应激和炎症反应的抑制作用[J].实用药物与临床,2017,20(2):140-143
[6]高全彩,吴红葵,林小娟.白芍总苷对稳定期慢性心力衰竭的疗效及对炎症水平的影响[J].临床心血管病杂志,2018,34(9):918-921
[7]史晴晴,杜欢,于红梅,等.白芍总苷对全脑缺血再灌注损伤保护作用的研究[J].中国中医急症,2017,26(7):1172-1174
[8]杨珊珊,董晨,关凤军,等.白芍总苷对阿霉素肾病大鼠肾脏的保护作用[J].吉林医学,2016,37(10):2392-2394
[9]李佳.白芍总苷联合盐酸贝那普利片治疗慢性肾小球肾炎及对IL-18、IL-6含量的影响[J].中医中药,2017,15(10):190-191
[10]梁自豪,徐强,陈臻毅,等.建立急性肾功能衰竭实验动物模型的研究进展[J].安徽医药,2016,20(5):1000-1001
[11]向丽,林波,张祎,等.保肾颗粒对庆大霉素所致大鼠急性肾功能衰竭的保护作用[J].中药药理与临床,2014,30(4):104-108
[12]钟瑜萍,李海燕,宫仁豪,等.大黄黄芪不同配伍比例对慢性肾衰竭大鼠24 h UPQ、Scr、BUN及肾脏形态学的影响[J].中药药理与临床,2016,32(4):63-66
[13]周懂晶,刘玉品,陈志远,等.3.0T ASL-fMRI评价灯盏花素对大鼠对比剂急性肾损伤的保护作用[J].暨南大学学报(自然科学与医学版),2016,37(3):253-258
[14]高双荣,孙翠英,郑燕飞,等.糖肾清对DN模型大鼠肾组织形态学的影响[J].中国实验方剂学杂志,2011,17(14):156-159
[15]Quiros Y,Ferreira L,Sancho-Martínez S M,et al.Subnephrotoxic doses of gentamicin predispose animals to developing acute kidney injury and to excrete ganglioside M2 activator protein[J].Kidney Int,2010,78(10):1006-1015
[16]Chen TH,Liao FT,Yang YC,et al.Inhibition of inducible nitric oxide synthase ameliorates myocardial ischemia/reperfusion injury induced acute renal injury[J].Transpl P,2014,46(4):1123-1126
[17]何彩云,周少雄,沈永坚,等.早期糖尿病肾病患者联合检测m ALB、β-2-MG、NAG的临床意义[J].吉林医学,2018,39(5):816-818
[18]崔蓉,魏薇,卜一珊.药物性肾损害诊断中肾损害标志物的研究进展[J].天津药学,2017,29(4):62-65
[19]王景霞,邓文伟,齐亚灵.丹参和川芎嗪对庆大霉素肾毒性的保护作用[J].中国手术学杂志,2002,11(2):247-249
[20]董丹娜,徐应军,于明忠.维持性血液透析患者的微炎症状态对其肾性贫血的影响[J].中国煤炭工业医学杂志,2016,19(10):1441-1444
[2]Teslariu O,Pasca AS,Mititelu-Tartau L,et al.The protective effects of zinc in experimental gentamicin induced acute renal failure in rats[J].J Physiol Pharmacol,2016,67(5):751-757
[3]El-Ashker M,Abdelhamid F,Risha E,et al.Vitamin C ameliorates gentamicin-induced acute kidney injury in equines:an experimental study[J].J Equine Vet Sci,2015,35(3):238-243
[4]李明,刘勇强,敖华,等.葛根素减轻庆大霉素诱导的大鼠急性肾损伤[J].中国实验方剂学杂志,2017,23(17):177-182
[5]王晓纲.白芍总苷对动脉粥样硬化大鼠氧化应激和炎症反应的抑制作用[J].实用药物与临床,2017,20(2):140-143
[6]高全彩,吴红葵,林小娟.白芍总苷对稳定期慢性心力衰竭的疗效及对炎症水平的影响[J].临床心血管病杂志,2018,34(9):918-921
[7]史晴晴,杜欢,于红梅,等.白芍总苷对全脑缺血再灌注损伤保护作用的研究[J].中国中医急症,2017,26(7):1172-1174
[8]杨珊珊,董晨,关凤军,等.白芍总苷对阿霉素肾病大鼠肾脏的保护作用[J].吉林医学,2016,37(10):2392-2394
[9]李佳.白芍总苷联合盐酸贝那普利片治疗慢性肾小球肾炎及对IL-18、IL-6含量的影响[J].中医中药,2017,15(10):190-191
[10]梁自豪,徐强,陈臻毅,等.建立急性肾功能衰竭实验动物模型的研究进展[J].安徽医药,2016,20(5):1000-1001
[11]向丽,林波,张祎,等.保肾颗粒对庆大霉素所致大鼠急性肾功能衰竭的保护作用[J].中药药理与临床,2014,30(4):104-108
[12]钟瑜萍,李海燕,宫仁豪,等.大黄黄芪不同配伍比例对慢性肾衰竭大鼠24 h UPQ、Scr、BUN及肾脏形态学的影响[J].中药药理与临床,2016,32(4):63-66
[13]周懂晶,刘玉品,陈志远,等.3.0T ASL-fMRI评价灯盏花素对大鼠对比剂急性肾损伤的保护作用[J].暨南大学学报(自然科学与医学版),2016,37(3):253-258
[14]高双荣,孙翠英,郑燕飞,等.糖肾清对DN模型大鼠肾组织形态学的影响[J].中国实验方剂学杂志,2011,17(14):156-159
[15]Quiros Y,Ferreira L,Sancho-Martínez S M,et al.Subnephrotoxic doses of gentamicin predispose animals to developing acute kidney injury and to excrete ganglioside M2 activator protein[J].Kidney Int,2010,78(10):1006-1015
[16]Chen TH,Liao FT,Yang YC,et al.Inhibition of inducible nitric oxide synthase ameliorates myocardial ischemia/reperfusion injury induced acute renal injury[J].Transpl P,2014,46(4):1123-1126
[17]何彩云,周少雄,沈永坚,等.早期糖尿病肾病患者联合检测m ALB、β-2-MG、NAG的临床意义[J].吉林医学,2018,39(5):816-818
[18]崔蓉,魏薇,卜一珊.药物性肾损害诊断中肾损害标志物的研究进展[J].天津药学,2017,29(4):62-65
[19]王景霞,邓文伟,齐亚灵.丹参和川芎嗪对庆大霉素肾毒性的保护作用[J].中国手术学杂志,2002,11(2):247-249
[20]董丹娜,徐应军,于明忠.维持性血液透析患者的微炎症状态对其肾性贫血的影响[J].中国煤炭工业医学杂志,2016,19(10):1441-1444