人工蝉花子实体对庆大霉素所致小鼠急性肾衰竭的影响及机制研究
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摘要
目的:研究人工蝉花子实体对庆大霉素所致小鼠急性肾衰竭的影响,并初步探讨其可能的作用机制。方法:将48只小鼠随机分为空白组(生理盐水)、模型组(生理盐水)、维拉帕米组(阳性对照,21.43 mg/kg)和人工蝉花子实体高、中、低剂量组(5、2.5、1.25 g/kg),每组8只。除空白组外,其余各组小鼠均腹腔注射庆大霉素200 mg/kg制备急性肾衰竭模型。各组小鼠于每次注射庆大霉素2 h后灌胃相应药物,每天1次,连续7 d。末次给药4 h后,测定各组小鼠血清中尿素氮(BUN)、血肌酐(Scr)和总蛋白含量,计算肾指数,测定肾组织中丙二醛(MDA)、超氧化岐化酶(SOD)含量及Na+-K+-ATP酶活性,肉眼及苏木精-伊红(HE)染色后显微镜下观察各组小鼠肾组织病理变化。结果:与空白组比较,模型组小鼠血清中BUN、Scr和肾组织中MDA含量以及肾指数均显著升高(P<0.01),血清中总蛋白含量以及肾组织中SOD含量和Na+-K+-ATP酶活性均显著降低(P<0.01);肉眼观察肾组织出现肿大、充血等病理变化,显微镜下可见肾组织发生肾小管上皮细胞重度颗粒、空泡样变性以及上皮细胞大量脱落等病理损伤。与模型组比较,各给药组小鼠血清中BUN、Scr和肾组织中MDA含量以及肾指数均显著降低(P<0.01),人工蝉花子实体高、中剂量组小鼠肾组织中SOD含量以及各给药组小鼠血清中总蛋白含量和肾组织中Na+-K+-ATP酶活性均显著升高(P<0.01);各给药组小鼠肾组织的病理损伤也不同程度好转,其中尤以人工蝉花子实体高、中剂量组改善最为明显。结论:人工蝉花子实体对庆大霉素所致小鼠急性肾衰竭具有显著的保护作用,其作用机制可能与减轻肾损伤及抗氧化作用有关。
OBJECTIVE:To study the effects of artificial Isaria cicadae cystocarp on gentamicin-induced acute renal failure in mice,and to investigate potential mechanism preliminarily. METHODS:Totally 48 mice were randomly divided into blank group(normal saline),model group(normal saline),verapamil group(positive control,21.43 mg/kg),artificial I. cicadae cystocarp high-dose,moderate-dose and low-dose groups(5,2.5,1.25 g/kg),with 8 mice in each group. Except for blank group,other groups were given gentamicin 200 mg/kg intraperitoneally to induce acute renal failure model;2 h after intraperitoneal injection of gentamicin,each group was given relevant medicine intragastrically,once a day,for consecutive 7 d. 4 h after last administration,the contents of BUN,Scr and total protein in serum were determined,and renal indexes were calculated. The contents of MDA,SOD and activity of Na+-K+-ATP enzyme in renal tissue were determined;the changes of renal histopathological were observed by naked eye or microscope after HE staining. RESULTS:Compared with blank group,the serum contents of BUN and Scr,the content of MDA in renal tissue and renal indexes were increased significantly in model group(P<0.01);the serum content of total protein,the content of SOD and activity of Na+-K+-ATP enzyme in renal tissue were decreased significantly(P<0.01). The pathological changes of renal tissue were observed by naked eye,such as swelling,congestion. Pathological injury of renal tissue was founded under microscope,such as severe granularity and vacuolar changes in renal tubular epithelial cells,epithelial cell exfoliation. Compared with model group,serum contents of BUN and Scr,content of MDA and renal indexes of renal tissue were decreased significantly in each administration group(P<0.01);SOD content of renal tissue in artificial I. cicadae cystocarp high-dose and medium-dose groups,activity of Na+-K+-ATP enzyme in renal tissue in each administration group were increased significantly(P<0.01). The pathological injury of renal tissue in different administration groups were also improved to varying degrees,especially artificial I. cicadae cystocarp high-dose and medium-dose groups. CONCLUSIONS:The artificial I. cicadae cystocarp has a significant protective effect on the gentamicin-induced acute renal failure in mice,the mechanism of which may be related to the alleviation of renal damage and antioxidant function.
OBJECTIVE:To study the effects of artificial Isaria cicadae cystocarp on gentamicin-induced acute renal failure in mice,and to investigate potential mechanism preliminarily. METHODS:Totally 48 mice were randomly divided into blank group(normal saline),model group(normal saline),verapamil group(positive control,21.43 mg/kg),artificial I. cicadae cystocarp high-dose,moderate-dose and low-dose groups(5,2.5,1.25 g/kg),with 8 mice in each group. Except for blank group,other groups were given gentamicin 200 mg/kg intraperitoneally to induce acute renal failure model;2 h after intraperitoneal injection of gentamicin,each group was given relevant medicine intragastrically,once a day,for consecutive 7 d. 4 h after last administration,the contents of BUN,Scr and total protein in serum were determined,and renal indexes were calculated. The contents of MDA,SOD and activity of Na+-K+-ATP enzyme in renal tissue were determined;the changes of renal histopathological were observed by naked eye or microscope after HE staining. RESULTS:Compared with blank group,the serum contents of BUN and Scr,the content of MDA in renal tissue and renal indexes were increased significantly in model group(P<0.01);the serum content of total protein,the content of SOD and activity of Na+-K+-ATP enzyme in renal tissue were decreased significantly(P<0.01). The pathological changes of renal tissue were observed by naked eye,such as swelling,congestion. Pathological injury of renal tissue was founded under microscope,such as severe granularity and vacuolar changes in renal tubular epithelial cells,epithelial cell exfoliation. Compared with model group,serum contents of BUN and Scr,content of MDA and renal indexes of renal tissue were decreased significantly in each administration group(P<0.01);SOD content of renal tissue in artificial I. cicadae cystocarp high-dose and medium-dose groups,activity of Na+-K+-ATP enzyme in renal tissue in each administration group were increased significantly(P<0.01). The pathological injury of renal tissue in different administration groups were also improved to varying degrees,especially artificial I. cicadae cystocarp high-dose and medium-dose groups. CONCLUSIONS:The artificial I. cicadae cystocarp has a significant protective effect on the gentamicin-induced acute renal failure in mice,the mechanism of which may be related to the alleviation of renal damage and antioxidant function.
引文
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[17]贾支俊,冯雪凤,郭利利,等.肾小球滤过率、血清肌酐及24 h尿蛋白定量与狼疮肾炎病程相关性研究[J].实用医学杂志,2008,24(3):376-377.
[18]陈炜,张雪元,刘源才,等.不同产地冬虫夏草对硫酸庆大霉素致急性肾损伤的保护作用[J].中国药师,2015,18(12):2042-2045.
[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].局解手术学杂志,2002,11(2):247-249.
[2]陈香美.当前肾脏病的研究热点[J].中华内科杂志,2002,2(2):14-17.
[3]浙江省卫生厅.浙江省中药炮制规范[M].杭州:浙江科学技术出版社,1994:3471.
[4]卞智慧,于瑞莲,魏思敏,等.蝉花、蛹虫草和冬虫夏草药材中脂肪酸含量的比较研究[J].中国药房,2017,28(30):4252-4256.
[5]蒋宁,高大伟,林金盛,等.蝉花的研究进展[J].江苏农业科学,2017,45(8):11-14.
[6]李忠,刘爱英,金道超.蝉拟青霉深层发酵的研究[J].河北大学学报(自然科学版),2010,30(6):682-687.
[7]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.
[8]全丽.贝尼地平及维拉帕米干预UUO大鼠肾间质纤维化的实验研究[D].衡阳:南华大学,2015.
[9]闵旸,戚蓓茵,谢炜,等.蝉花菌丝体抗肾功能衰竭药效学研究[J].中国药理通讯,2004,21(3):19-20.
[10]何鹏飞,高敏,张娅,等.急慢性肾功能衰竭动物模型研究进展[J].云南中医中药杂志,2017,38(12):80-84.
[11]赖学莉,黄颂敏.急性肾功能衰竭药物治疗的最新进展[J].国外医学:泌尿系统分册,2005,25(5):49-52.
[12]黄颂敏,刘先蓉.肾脏疾病鉴别诊断与治疗学[M].北京:人民军医出版社,2006:115-121.
[13]石桂珍,和彩玲,王浩玥,等.中医治疗糖尿病肾病蛋白尿研究进展[J].中医药临床杂志,2017,29(2):285-288.
[14]周建华.蛋白尿的发生机制研究进展[J].中国实用儿科杂志,2016,31(11):808-812.
[15]李健,李显文,杨孟雪,等.血清胱抑素C、尿微量白蛋白/肌酐比值联合测定在老年2型糖尿病早期肾病诊断的价值[J].中国医学创新,2015,12(1):4-6.
[16]李星亚.茶多糖和茶多酚对糖尿病大鼠血糖血脂及肾脏的保护作用[D].青岛:中国海洋大学,2013.
[17]贾支俊,冯雪凤,郭利利,等.肾小球滤过率、血清肌酐及24 h尿蛋白定量与狼疮肾炎病程相关性研究[J].实用医学杂志,2008,24(3):376-377.
[18]陈炜,张雪元,刘源才,等.不同产地冬虫夏草对硫酸庆大霉素致急性肾损伤的保护作用[J].中国药师,2015,18(12):2042-2045.
[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].局解手术学杂志,2002,11(2):247-249.