蛋白激酶受体2在糖尿病大鼠肾组织中的表达与意义

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1、3．免疫组化显示，糖尿病大鼠PAR．2主要表达于近曲小管上皮细胞，肾小球略有表达，而对照组表达很少。经病理图像分析软件统计显示，与对照组相比，糖尿病大鼠PAR．2表达明显增加，且随着病程延长呈上升趋势，到20W有轻微下降，但用药组与糖尿病组之间没有统计学差异。RT．PCR结果也显示，与对照组相比糖尿病大鼠PAR．2表达明显增加。4．病理图像分析软件结果显示，PAR．2的蛋白表达水平与肌酐清除率呈负相关，r为．0．819(P<0．05)；与24小时尿蛋白呈正相关，r为0．908(P<0．05)。结论：PAR．2早期表达于糖

2、尿病肾病大鼠的近曲小管上皮细胞，肾组织PAR．2表达的变化趋势提示，PAR．2可能参与了糖尿病肾病的肾间质纤维化过程。ATl受体拮抗剂延缓糖尿病肾病纤维化的作用可能与PAR．2所介导的作用途径无关。关键词：蛋白激酶受体2糖尿病肾病肾间质纤维化2vatedyratsSupervisor：ProfessorZhengnanGaoVice—supervisor：ProfessorLijingChengMajor：InternalMedicineAbstraetObjective：Diabeticnephropathyisthe

3、mostcommoncauseofend—stageofrenaldiseaseintheworld．Itisaserioushazardtohumanhealth．Diabeticnephropathyischaracterizedbyglomerularhypertrophy，mesan—gialmatrixexpansionandglomerularbasementmembranethickeningfollowedbyglomerulosclerosis；tubularbasementmembranethicke

4、ningandtubulointerstitialfibrosis．Inrecentyears，protease-activatedreceptorsfamilyproteininroleofrenaldiseaseshasbeenconcerned．Inthisstudy，weinvestigatedexpressionofSmad1inkidneyofdiabeticnephropathyrattoexploretheroleofproteaseactivatedreceptor·2intubulointerstit

5、ialfibrosisofdiabeticnephropathyrats．Methods：60Sprague-Dawleyratswererandomlydividedintothreegroups，controlgroupincluded15rats，anddiabeticgroupandtreatmentgroupwererespectively25and20rats．Streptozotocin(55mg／kg)induceddiabetics，ratsreceivinganinjectionofcitratebu

6、fferwereusedascontrols．TreatmentgroupratsweretreatedwiththeARB，olmesarta(O．6mg／kg．d)aftertowweeks，otherratstreatedwithnomalsaline．Theratsweresacrificedat2w，4w，8w，12wand20wrespectinely．Glycosylatedhemoglobin，serumcreatinineandkidneyweightindexweremeasuredineachrat

7、s，whilecreatinineandalbuminweremeasuredfroma24一hurinecollection，meanwhilekidneysectionswereobservedbyeleetronmicros-copy，massonstaining，periodicacidsilvermethenamine(PASM)andperiodicacidSchiff(PAS)usedtomonitortherenalpathologicalchanges．TheproteinexpressionofPAR

8、-2andcollagenⅣinkidneyweredetectedbyimmunohistochemistry，themRNAexpressionofPAR-2wasdetectedbyreversetranscriptionpolymerasechainreaction．Usinganimageanalyzerw