牛磺酸对脂多糖诱导小鼠急性肾损伤的保护作用及机制
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摘要
目的观察牛磺酸对脂多糖(LPS)诱导小鼠急性肾损伤的保护作用,并从氧化应激、炎症反应两方面探讨其可能机制。方法 30只雄性SPF级KM小鼠随机分为3组(n=10):假手术组、模型组(LPS组)和治疗组(牛磺酸+LPS组)。腹腔注射LPS (10 mg/kg)方法复制小鼠急性肾损伤模型,假手术组注射同样剂量生理盐水,治疗组于术前7 d开始,用牛磺酸溶液(0. 2 g/0. 2 m L)灌胃,1次/d,持续8 d。造模24 h后眼球取血,分离血清检测超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH)、尿素氮(BUN)、血肌酐(Scr)和丙二醛(MDA)含量;收集尿液检测BUN、尿蛋白(PRO)和尿肌酐(Ucr)的含量;取肾脏计算肾脏系数(renal index),ELISA试剂盒检测肾组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)含量,并取部分肾脏组织做HE染色切片,观察肾组织损伤情况。结果与假手术组相比,模型组小鼠血清中BUN、Scr、MDA含量明显增加,SOD和GSH含量明显降低;尿液中BUN、PRO、Ucr含量明显增加;肾组织中TNF-α和IL-1β含量增加,组织结构明显破坏,肾系数增加。与模型组相比,治疗组小鼠以上指标明显改善。结论牛磺酸对LPS诱导的急性肾损伤有明显保护作用,其机制与改善氧化应激和抑制肾组织炎性反应有关。
Objective To investigate the effect and mechanism of taurine( Tau) on lipopolysaccharide-induced acute kidney injury of mice. Methods Thirty male KM mice were randomly divided into 3 groups( n = 10),sham group,LPS group and Tau + LPS group. The acute kidney injury model was induced by intraperitoneal injection of LPS( 10 mg/kg),while the sham group received same dosage of saline instead of LPS. Tau + LPS group was given with taurine solution( 0. 2 g/0. 2 mL in distilled water) once daily,7 days before LPS injection,and lasted for 8 days. Twenty-four hours after LPS or saline injection,blood was collected for testing the contents of superoxide dismutase( SOD),glutathione peroxidase( GSH),urea nitrogen( BUN),serum creatinine( Scr) and malondialdehyde( MDA) in serum. Urine levels of BUN,urine protein( PRO) and creatinine( Ucr) were measured. Renal expression of tumor necrosis factor-α( TNF-α) and interleukin-1β( IL-1β) were measured by ELISA kits. HE staining and renal index were employed for determining the damage of renal tissues. Results Compared with sham group,LPS injection significantly increased BUN,Scr and MDA in serum; reduced SOD and GSH in serum; increased BUN,PRO and Ucr in urine; and increased TNF-α and IL-β expression in renal tissue which also showed typical tissue damage in HE staining slides. Compared with LPS group,consecutive delivery of taurine significantly ameliorated the above indicators. Conclusion Taurine has protective effect on LPS-induced acute kidney injury from inhibiting oxidative stress and inflammatory reaction in renal tissues.
Objective To investigate the effect and mechanism of taurine( Tau) on lipopolysaccharide-induced acute kidney injury of mice. Methods Thirty male KM mice were randomly divided into 3 groups( n = 10),sham group,LPS group and Tau + LPS group. The acute kidney injury model was induced by intraperitoneal injection of LPS( 10 mg/kg),while the sham group received same dosage of saline instead of LPS. Tau + LPS group was given with taurine solution( 0. 2 g/0. 2 mL in distilled water) once daily,7 days before LPS injection,and lasted for 8 days. Twenty-four hours after LPS or saline injection,blood was collected for testing the contents of superoxide dismutase( SOD),glutathione peroxidase( GSH),urea nitrogen( BUN),serum creatinine( Scr) and malondialdehyde( MDA) in serum. Urine levels of BUN,urine protein( PRO) and creatinine( Ucr) were measured. Renal expression of tumor necrosis factor-α( TNF-α) and interleukin-1β( IL-1β) were measured by ELISA kits. HE staining and renal index were employed for determining the damage of renal tissues. Results Compared with sham group,LPS injection significantly increased BUN,Scr and MDA in serum; reduced SOD and GSH in serum; increased BUN,PRO and Ucr in urine; and increased TNF-α and IL-β expression in renal tissue which also showed typical tissue damage in HE staining slides. Compared with LPS group,consecutive delivery of taurine significantly ameliorated the above indicators. Conclusion Taurine has protective effect on LPS-induced acute kidney injury from inhibiting oxidative stress and inflammatory reaction in renal tissues.
引文
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[10]朱伟,曾甫清,刘聪,等.牛磺酸对体外冲击波碎石致肾损伤保护的实验研究[J].华中科技大学学报:医学版,2007,36(5):630-632.
[11]孙玲玲,孙显露,朱宗令,等.牛磺酸对大鼠庆大霉素中毒性急性肾损伤的保护作用[J].齐鲁医学杂志,2007,22(5):377-379.
[12]Ripps H,Shen W.Review:taurine:a“very essential”amino acid[J].Mol Vis,2012,18:2673-2686.
[13]Zhu JB,Xu S,Li J,et al.Farnesoid X receptor agonist obeticholic acid inhibits renal inflammation and oxidative stress during lipopolysaccharide-induced acute kidney injury[J].Eur J Pharmacol,2018,838:60-68.
[14]An X,Shang F.RA-XII exerts anti-oxidant and anti-inflammatory activities on lipopolysaccharide-induced acute renal injury by suppressing NF-κB and MAPKs regulated by HO-1/Nrf2pathway.Biochem Biophys Res Commun,2018,495(3):2317-2323.
[15]高斌,高洪.氧自由基与细胞损伤[J].动物医学进展,2002,23(5):34-36.
[16]曹炜,尉亚辉,陈锦屏.蜂胶对氧自由基致鼠红细胞膜损伤的保护作用[J].食品科学,2002,23(5):118-120.
[17]候洪涛,裘艳梅,冯佳,等.姜黄素对非酒精性脂肪肝病大鼠肠道s Ig A及氧化应激的影响[J].广东医学,2018,39(8):1133-1136.
[18]林海洋,何涛,张剑辉.辛伐他汀对脓毒症早期大鼠血脂代谢及肝脏氧化应激的影响[J].广东医学,2017,38(21):3243-3246.
[19]孙振华,孙玉雪,徐筠茹,等.牛磺酸对鼠肝缺血-再灌流损伤的保护作用[J].中华急诊医学杂志,2005,14(11):920-921.
[20]张增雷,刘星,胡静,等.心肌缺血小鼠牛磺酸代谢和保护作用的分子机制[J].中华老年医学杂志,2018,38(16):3996-3999.
[21]孙喜家,王键,冯娅妮.七氟烷对脂多糖诱导小鼠肺损伤的保护作用及与Toll样受体4表达的关系[J].广东医学,2016,37(1):59-61.
[22]曹小飞,张德明,邓青南.LPS急性肺损伤老年大鼠肺巨噬细胞TLR4与IL-18 mRNA表达变化的对比研究[J].广东医学,2003,24(3):242-243.
[2]Zaqer RA,Johnson AC,Lund S,et al.Acute renal failure:determinants and characteristics of the injury-induced hyperinflammatory response[J].Am J Physiol Renal Physiol,2006,291(3):F546-F556.
[3]Dellinger RP,Levy MM,Carlet JM,et al.Surviving sepsis campaign international guidelines for management of severe sepsis and septic shock:2008[J].Crit Care Med,2008,36(4):296-327.
[4]温宝书,张敏.牛磺酸的细胞保护作用[J].中国药学杂志,1995,30(8):451-453.
[5]付凌,宋剑波,胡春燕,等.牛磺酸对脂多糖诱导的小鼠肝脏损伤的缓解作用[J].动物营养学报,2015,27(3):989-996.
[6]贾克,张立丰.氯化锰对大鼠纹状体和大脑皮层谷氨酸含量的影响[J].蚌埠医学院学报,2008,33(4):389-391.
[7]沈海涛,吴娜,王煜,等.牛磺酸对百草枯中毒大鼠肾损伤的作用及机制研究[J].中国病理生理杂志,2017,33(7):1295-1300.
[8]张立功,王力俊,于永慧,等.牛磺酸对糖尿病大鼠早期肾损伤与肾脏凝集素样氧化低密度脂蛋白受体1和胞间黏附分子1表达的影响[J].中华肾脏病杂志,2009,25(8):652-654.
[9]佟立权,乔海泉,宋光平,等.牛磺酸对大鼠小肠缺血再灌注后肝、肾损伤的保护作用[J].中国普通外科杂志,2006,15(7):512-515.
[10]朱伟,曾甫清,刘聪,等.牛磺酸对体外冲击波碎石致肾损伤保护的实验研究[J].华中科技大学学报:医学版,2007,36(5):630-632.
[11]孙玲玲,孙显露,朱宗令,等.牛磺酸对大鼠庆大霉素中毒性急性肾损伤的保护作用[J].齐鲁医学杂志,2007,22(5):377-379.
[12]Ripps H,Shen W.Review:taurine:a“very essential”amino acid[J].Mol Vis,2012,18:2673-2686.
[13]Zhu JB,Xu S,Li J,et al.Farnesoid X receptor agonist obeticholic acid inhibits renal inflammation and oxidative stress during lipopolysaccharide-induced acute kidney injury[J].Eur J Pharmacol,2018,838:60-68.
[14]An X,Shang F.RA-XII exerts anti-oxidant and anti-inflammatory activities on lipopolysaccharide-induced acute renal injury by suppressing NF-κB and MAPKs regulated by HO-1/Nrf2pathway.Biochem Biophys Res Commun,2018,495(3):2317-2323.
[15]高斌,高洪.氧自由基与细胞损伤[J].动物医学进展,2002,23(5):34-36.
[16]曹炜,尉亚辉,陈锦屏.蜂胶对氧自由基致鼠红细胞膜损伤的保护作用[J].食品科学,2002,23(5):118-120.
[17]候洪涛,裘艳梅,冯佳,等.姜黄素对非酒精性脂肪肝病大鼠肠道s Ig A及氧化应激的影响[J].广东医学,2018,39(8):1133-1136.
[18]林海洋,何涛,张剑辉.辛伐他汀对脓毒症早期大鼠血脂代谢及肝脏氧化应激的影响[J].广东医学,2017,38(21):3243-3246.
[19]孙振华,孙玉雪,徐筠茹,等.牛磺酸对鼠肝缺血-再灌流损伤的保护作用[J].中华急诊医学杂志,2005,14(11):920-921.
[20]张增雷,刘星,胡静,等.心肌缺血小鼠牛磺酸代谢和保护作用的分子机制[J].中华老年医学杂志,2018,38(16):3996-3999.
[21]孙喜家,王键,冯娅妮.七氟烷对脂多糖诱导小鼠肺损伤的保护作用及与Toll样受体4表达的关系[J].广东医学,2016,37(1):59-61.
[22]曹小飞,张德明,邓青南.LPS急性肺损伤老年大鼠肺巨噬细胞TLR4与IL-18 mRNA表达变化的对比研究[J].广东医学,2003,24(3):242-243.
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