葡萄籽原花青素对顺铂所致小鼠肾毒性作用的影响.pdf

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1、中国病理生理杂志ChineseJournalofPathophysiology2014，30(2)：313．317·313·[文章编号]1000-4718(2014)02—0313．05葡萄籽原花青素对顺铂所致小鼠肾毒性作用的影响高兆丽，刘广义，李星，胡昭，杨向东，江蓓，李究花(山东大学齐鲁医院泌尿内科，山东济南250012)[摘要]目的：探讨葡萄籽原花青素(GSP)对顺铂(CP)肾毒性作用的防护及可能机制。方法：雄性C57小鼠分为4组：正常对照组(N组，n=10)、CP组(腹腔注射20mS／kgCP，n=20)、GSP组(第1天及第3天灌胃GSP

2、500ms／kg，n=15)和CP+GSP组(腹腔注射CP30min前给予500ms／kgGSP灌胃，第3天灌胃等量的GSP，n=20)。给药后第5天取血，肾组织病理HE染色，应用蛋白印迹法和免疫组化法检测小鼠葡萄糖调节蛋白78(GRP78)和磷酸化细胞外信号调节激酶(p-ERK)的蛋白表达。结果：与N组比较，cP组肾脏指数升高，血尿素氮和血清肌酐水平升高(P<0．05)，肾病理损伤明显，’肾组织GRP78和p-ERK蛋白表达增加(P<0．05)。与cP组相比，CP+GSP组肾脏指数降低，血尿素氮和血清肌酐水平下降(P<0．05)，肾病理损伤减轻，

3、GRP78和p-ERK蛋白表达明显降低(P<0．05)。结论：GSP能明显降低CP所致的。肾毒性，其机制与GSP下调CP导致的内质网应激有关。[关键词]顺铂；葡萄籽原花青素；肾毒性；内质网应激[中图分类号]R595．4；R692．5[文献标志码]Adoi：10．3969／j．issn．1000—4718．2014．02．021Efectofgrapeseedpr0anth0cyanidinoncisplatin-inducednephrOt0xicityinmlCeGAOZhao—li，LIUGuang—yi，LIXing，HUZhao，YANGX

4、iang—dong，JIANGBei，LIXian．hua(DepartmentofNephrology，QiluHospitalofShandongUniversity，Jinan250012，China．E·mail：lixianhua@medmail．com．cn)[ABSTRACT]AIM：Tostudytheprotectiveeffectofgrapeseedproanthocyanidin(GSP)onnephrotoxicityin—ducedbycisplatin(CP)inmice．METHODS：MaleC57micewere

5、randomlydividedinto4groups：controlgroup(Ngroup，n=10)，CPgroup(intraperitonealinjectionofCPatdoseof20ms／kg，n=20)，GSPgroup(intragastricadminis—trationofGSPatdoseof500ms／kg，n=15)andCP+GSPgroup(intragastricadministrationofGSP30minpriortointra-peritonealinjectionofCPandintragastrica

6、dministrationofthesanledoseofGSP72hlater，n=20)．Onthe5thdayafterCPtreatment，bloodandkidneysampleswerecollected．TherenalpathologicalchangeswereexaminedbyHEstaining．Theproteinexpressionofglucose—regulatedprotein78(GRP78)andphosphorylatedextracellularsignal-regulatedkinase(p-ERK)w

7、asexaminedbyWesternblottingandimmunohistochemicalstaining．RESULTS：Renalindex，bloodureani—trogenandserumcreatinineweresignificantlyhigherinCPgroupthanthoseinNgroup．TherenaltissueswereheavilydamagedinCPgroup．TheproteinexpressionofGRP78andp-ERKincreasedinCPgroupcomparedwithNgroup

8、．GSPtreatmentalleviatedtheincreaseintherenalindex，bloodureani