基于Klotho研究三七总皂苷对大鼠肾缺血-再灌注损伤的保护机制  

Study on Protective Mechanism of Panax Notoginseng Saponins on Rats with Renal Ischemia Reperfusion Injury Based on Klotho

作　　者：庄高建 胡鸿运 杨英[1] 唐紫荆 孙轩龙 刘春燕[1] 唐群[1] ZHUANG Gao-jian;HU Hong-yun;YANG Ying;TANG Zi-jing;SUN Xuan-long;LIU Chun-yan;TANG Qun(Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学,湖南长沙410208

出　　处：《中国中医药信息杂志》2018年第11期31-35,共5页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(81503442);湖南中医药大学大学生研究性学习和创新性实验计划课题(2017-39);湖南省教育厅科研项目(17B197)

摘　　要：目的观察三七总皂苷对肾缺血-再灌注损伤大鼠Klotho蛋白表达的影响,探讨其对模型大鼠的保护机制。方法实验大鼠随机分为假手术组、模型组、阳性药组和三七总皂苷高、中、低剂量组,各给药组给予相应药物,每日1次。建立大鼠肾缺血-再灌注损伤模型,造模4 h后腹主动脉取血处死大鼠。检测大鼠血清尿素氮(BUN)、肌酐(SCr)水平及肾组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-Px)活性,HE染色观察肾组织形态变化,免疫组化检测Klotho、核因子-κB(NF-κB)p65蛋白的表达。结果与假手术组比较,模型组大鼠血清BUN、SCr水平明显升高(P<0.05),肾组织Klotho蛋白表达降低,NF-κB p65蛋白表达升高(P<0.05);与模型组比较,各给药组Klotho蛋白表达升高,NF-κB p65蛋白表达降低(P<0.05);与阳性药组比较,三七总皂苷高剂量组Klotho蛋白表达升高,NF-κB p65蛋白表达降低(P<0.05)。NF-κB p65蛋白表达与Klotho呈负相关(r=-0.895,P<0.05)。结论三七总皂苷可能通过上调Klotho蛋白表达,减少NF-κB p65蛋白表达,抑制氧化应激和对抗炎症,从而发挥保护肾脏作用。Objective To investigate the effects of Panax Notoginseng saponins(PNS)on protein expression of Klotho in rats with renal ischemia reperfusion injury;To discuss its protective mechanism for model rats.Methods Experimental rats were randomly divided into sham-operation group,model group,positive medicine group,PNS high-,medium-and low-dosage groups.Each administration group was given relevant medicine for gavage,once a day.Renal ischemia reperfusion injury model was established.Rats were sacrificed by taking blood from abdominal aorta after 4 hours of modeling.Serum levels of blood urea nitrogen(BUN),creatinine(SCr),malondialdehyde(MDA)content in kidney tissue,superoxide dismutase(SOD)activity and glutathione peroxidase(GSH-Px)activity were measured.HE staining was used to observe the morphological changes of renal tissue.The protein expressions of Klotho and NF-κB p65 were measured by immunohistochemical method.Results Compared with the sham-operation group,the levels of BUN and SCr in the model group increased significantly(P<0.05);protein expression of Klotho in renal tissue decreased and the protein expression of NF-κB p65 increased(P<0.05).Compared with the model group,the expression of Klotho increased but protein expression of NF-κB p65 decreased in each administration group(P<0.05);Compared with the positive medicine group,the expression of Klotho in PNS high-dosage group increased but protein expression of NF-κB p65 decreased(P<0.05).The protein expression of NF-κB p65 was negatively related to protein expression of Klotho(r=-0.895,P<0.05).Conclusion PNS can inhibit oxidative stress and anti-inflammatory effects through upregulating protein expression of Klotho,and reduce the protein expression of NF-κB p65,and thus exerts renal protective effects.

关 键 词：肾缺血-再灌注损伤 氧化应激 KLOTHO 三七总皂苷 大鼠 

分 类 号：R285.5[医药卫生—中药学]