天然产物研究与开发 ›› 2018, Vol. 30 ›› Issue (9): 1614-1620.doi: 10.16333/j.1001-6880.2018.9.024

• 开发研究 • 上一篇    下一篇

辣椒素对肾脏缺血再灌注损伤的保护作用及TRPV1通路相关性研究

廖盼丽,黄霖*   

  1. 华中科技大学同济医学院附属武汉儿童医院,武汉 443000
  • 出版日期:2018-10-08 发布日期:2018-10-10
  • 基金资助:

    国家自然科学基金(81470994)

Protective Effect of Capsaicin on Renal Ischemia-reperfusion Injury and the Correlation with TRPV1 Pathway

LIAO Pan-li,HUANG Lin*   

  1. Wuhan Childrens Hospital(Wuhan Maternal and Child Healthcare Hospital),Tongji Medical College,Huazhong University of Science & Technology,Wuhan 443000,China
  • Online:2018-10-08 Published:2018-10-10

摘要: 研究辣椒素的抗肾脏缺血再灌注损伤(I/R)的作用及可能的作用机制。将SD大鼠随机分为假手术组、模型组、低剂量辣椒素组(4 μg/kg)、中剂量辣椒素组(8 μg/kg)、和高剂量辣椒素组(16 μg/kg)。辣椒素组在缺血前45分钟通过腹腔注射(4、8、16)μg/kg的辣椒素,辣椒素组在缺血前45分钟通过腹腔注射(4、8、16)μg/kg的辣椒素,假手术组和模型组在缺血前45分钟通过腹腔注射等体积生理盐水。利用ELISA检测血清中肌酐(Cr)和尿素氮(BUN)的含量;过碘酸雪夫染色(PAS)染色检测肾组织病理形态;酶法检测肾脏线粒体Ca2 +-ATP 酶和Na+-K+-ATP 酶活性;硫代巴比妥酸比色法(TBA)检测肾脏线粒体丙二醛(MDA) 的含量;黄嘌呤氧化酶法检测肾脏线粒体超氧化物歧化酶(SOD)活性;比色法检测肾脏线粒体谷胱甘肽过氧化物酶(GPx)和过氧化氢酶(CAT)活性;免疫蛋白印记法(Western bloting)检测瞬时感受器电位香草酸受体-1 (Transient Receptor Potential Vanilloid-1,TRPV1)和p-TRPV1蛋白水平;高效液相色谱法检测肾脏线粒体三磷酸腺苷(ATP) 、二磷酸腺苷(ADP)、一磷酸腺苷(AMP)含量,并计算和腺苷酸池(ATP +ADP +AMP)含量。结果显示:与假手术组相比,模型组Cr、BUN和线粒体MDA的含量以及p-TRPV1表达水平和肾组织病理损伤均明显增加,而线粒体SOD、GPx、CAT、Ca2 +-ATP 酶和Na+-K+-ATP 酶活性以及ATP、ADP、AMP和ATP +ADP +AMP含量均明显降低,而TRPV1表达无差异;与模型组相比,利用辣椒素预处理可呈剂量依赖性减少Cr、BUN和线粒体MDA的含量以及肾组织病理损伤,并可呈剂量依赖性增加肾脏线粒体SOD、GPx、CAT、Ca2 +-ATP 酶和Na+-K+-ATP 酶活性以及p-TRPV1表达和ATP、ADP、AMP和ATP +ADP +AMP含量,而TRPV1表达无差异;以上结果均表明辣椒素减轻大鼠肾缺血再灌注损伤与抑制线粒体脂质过氧化反应相关。

关键词: 辣椒素, 肾脏缺血再灌注损伤, 线粒体, 脂质过氧化

Abstract: To study the protective effect and potential mechanism of capsaicin on renal ischemia reperfusion injury (I/R).The SD rats were divided into Sham group,model group,low dose capsaicin group (4 μg/kg),middle dose capsaicin group (8 μg/kg),and high dose capsaicin group (16 μg/kg).The capsaicin grorps were pretreated with capsaicin(4、8、16)μg/kg at 45 min before ischemia by intraperitoneal injection.The Sham and model grorps were pretreated with the equal volume of saline at 45 min before ischemia by intraperitoneal injection..The content of ATP、ADP、AMP and ATP +ADP +AMP in mitochondrialof kidney were examined by high performance liquid chromatography;The content of creatinine (Cr) and urea nitrogen (BUN) in serum were evaluated by ELISA;PAS staining was used to measure renal pathological injury;The activity of Ca2 +-ATP and Na+-K+-ATP in mitochondrial were evaluated by enzymatic method;The content of malondialdehyde (MDA) in mitochondrial was examined by thiobarbituric acid colorimetric method (TBA);The activation of superoxide dismutase (SOD),glutathione peroxidase (GPx) and catalase (CAT) in mitochondrial of kidney were detected by xanthine oxidase and Colorimetry,respectively.Western bloting was used to mesuare the expression of p-TRPV1 and TRPV1.The results showed that:compared with Control group,the model group has higher expression of p-TRPV1,more content of Cr、BUN and MDA and more serious renal pathological injury with lower activity of SOD、GPx、CAT、Ca2 +-ATP and Na+-K+-ATP and ATP、ADP、AMP and ATP +ADP +AMP content in mitochondrialof kidney with no difference on the TRPV1expression;compared with the model group,the capsaicin pretreatment can significantly reduce the content of Cr,BUN and MDA and the pathological damage of kidney with significantly increasing activity of SOD、GPx、CAT、Ca2 +-ATP and Na+-K+-ATP and higher content of ATP、ADP、AMP、ATP +ADP +AMP and p-TRPV with no difference on the TRPV1expression;Therefore,capsaicin can protect rats against renal ischemia reperfusion injury which is associated with inhibition of kidney mitochondrial lipid peroxidation.

Key words: capsaicin, renal ischemia reperfusion injury, mitochondrial, lipid peroxidation

中图分类号: 

R285.5 Q946.9