中华肾脏病杂志
中華腎髒病雜誌
중화신장병잡지
2010年
4期
279-283
,共5页
王显%张伯科%沈雯雯%周琪
王顯%張伯科%瀋雯雯%週琪
왕현%장백과%침문문%주기
多柔比星%纤维化%受体,趋化因子%纤维细胞
多柔比星%纖維化%受體,趨化因子%纖維細胞
다유비성%섬유화%수체,추화인자%섬유세포
Doxorubicin%Fibrosis%Receptors,chemokine%Fibrocyte
目的 以多柔比星慢性肾损害大鼠为对象,探讨纤维细胞及其趋化因子受体7(CCR7)在肾纤维化中的作用.方法 雄性SD大鼠52只,随机分为对照组(n=20)、模型组(n=32).实验开始第1、2周第1天,模型组重复给予多柔比星(4 mg/kg)尾静脉注射,对照组给予等量生理盐水,首次给药后第4、7、10、13周末取血、尿检测生化指标;并于对照组和模型组分别随机选取5只和8只大鼠处死留取肾组织,通过Masson染色观察肾脏病理变化.使用肾小球硬化指数(GSI)和肾小管间质损伤指数(TII)评估肾脏病变程度;免疫组化检测CD45、Ⅰ型胶原和CCR7表达.结果 与对照组相比,第7周末模型组血三酰甘油水平(mmol/L)升高(2.57±1.19比0.76±0.11,P<0.01)、血总胆固醇水平(mmol/L)升高(6.79±1.47比1.29±0.27,P<0.01),血清白蛋白水平(g/L)降低(21.4l±2.11比34.64±0.96,P<0.01);24 h尿蛋白排出量(mg)明显增加(568±102比21±6,P<0.01);肾小球系膜基质明显增多,肾小管多灶性萎缩和扩张,管腔内可见蛋白管型.GSI及TII随时间延长逐渐升高(P<0.05).连续切片观察肾间质出现CD45、Ⅰ型胶原双阳性细胞.CD45和CCR7阳性细胞第7周数量最多,后逐渐减少(P<0.01).结论 纤维细胞可能参与肾纤维化过程,在早期发挥作用,其由外周血迁移到组织可能与CCR7有关.
目的 以多柔比星慢性腎損害大鼠為對象,探討纖維細胞及其趨化因子受體7(CCR7)在腎纖維化中的作用.方法 雄性SD大鼠52隻,隨機分為對照組(n=20)、模型組(n=32).實驗開始第1、2週第1天,模型組重複給予多柔比星(4 mg/kg)尾靜脈註射,對照組給予等量生理鹽水,首次給藥後第4、7、10、13週末取血、尿檢測生化指標;併于對照組和模型組分彆隨機選取5隻和8隻大鼠處死留取腎組織,通過Masson染色觀察腎髒病理變化.使用腎小毬硬化指數(GSI)和腎小管間質損傷指數(TII)評估腎髒病變程度;免疫組化檢測CD45、Ⅰ型膠原和CCR7錶達.結果 與對照組相比,第7週末模型組血三酰甘油水平(mmol/L)升高(2.57±1.19比0.76±0.11,P<0.01)、血總膽固醇水平(mmol/L)升高(6.79±1.47比1.29±0.27,P<0.01),血清白蛋白水平(g/L)降低(21.4l±2.11比34.64±0.96,P<0.01);24 h尿蛋白排齣量(mg)明顯增加(568±102比21±6,P<0.01);腎小毬繫膜基質明顯增多,腎小管多竈性萎縮和擴張,管腔內可見蛋白管型.GSI及TII隨時間延長逐漸升高(P<0.05).連續切片觀察腎間質齣現CD45、Ⅰ型膠原雙暘性細胞.CD45和CCR7暘性細胞第7週數量最多,後逐漸減少(P<0.01).結論 纖維細胞可能參與腎纖維化過程,在早期髮揮作用,其由外週血遷移到組織可能與CCR7有關.
목적 이다유비성만성신손해대서위대상,탐토섬유세포급기추화인자수체7(CCR7)재신섬유화중적작용.방법 웅성SD대서52지,수궤분위대조조(n=20)、모형조(n=32).실험개시제1、2주제1천,모형조중복급여다유비성(4 mg/kg)미정맥주사,대조조급여등량생리염수,수차급약후제4、7、10、13주말취혈、뇨검측생화지표;병우대조조화모형조분별수궤선취5지화8지대서처사류취신조직,통과Masson염색관찰신장병리변화.사용신소구경화지수(GSI)화신소관간질손상지수(TII)평고신장병변정도;면역조화검측CD45、Ⅰ형효원화CCR7표체.결과 여대조조상비,제7주말모형조혈삼선감유수평(mmol/L)승고(2.57±1.19비0.76±0.11,P<0.01)、혈총담고순수평(mmol/L)승고(6.79±1.47비1.29±0.27,P<0.01),혈청백단백수평(g/L)강저(21.4l±2.11비34.64±0.96,P<0.01);24 h뇨단백배출량(mg)명현증가(568±102비21±6,P<0.01);신소구계막기질명현증다,신소관다조성위축화확장,관강내가견단백관형.GSI급TII수시간연장축점승고(P<0.05).련속절편관찰신간질출현CD45、Ⅰ형효원쌍양성세포.CD45화CCR7양성세포제7주수량최다,후축점감소(P<0.01).결론 섬유세포가능삼여신섬유화과정,재조기발휘작용,기유외주혈천이도조직가능여CCR7유관.
Objective To investigate the effect of fibrocytes and chemokine recepter 7(CCR7)on the process of renal fibrosis induced by adriamycin in rats.Methods Male Sprague-Dawhy(SD)8 weeks old rats(n=52)were divided into two groups randomly,normal control group(CG,n= 20)and model group(MG,n=32).MG rats were injected with 4 mg/kg of adriamycin via tail vein on the first day of the 1st and 2nd week,respectively,while CG rats received 0.9% sodium chloride solution injection of equal volume at the same time.The urine and serum samples were measured at the end of 4,7,10 and 13 weeks after the first administration of adriamycin to observe biochemical changes,while the renal tissue of rats was obtained to evaluate renal histological and uhrastructural changes by glomerulosclerosis index and tubulointerstitial index,and to analyze the expression of CD45,collagen Ⅰ and CCR7 by immunohistochemistry.Results Compared with CG,levels of 24 h urine protein excretion rate(mg,568±102 vs 21±6,P<0.01),serum cholesterol(CHO,mmol/L,6.79±1.47 vs 1.29±0.27,P<0.01)and triglyceride(TG,mmol/L,2.57±1.19 vs 0.76±0.11,P<0.01)increased significantly,whereas serum albumin(Alb,g/L,21.41±2.11 vs 34.64±0.96,P <0.01)decreased significantly in the 7th week in MG.The proliferation of mesangial cells,the accumulation of the extracellular matrix and atrophyin or extension of renal tubules in MG were more remarkable than those in CG.There were some cells which expressed CD45 and collagen Ⅰ simultaneously in the serial sections of renal tissue and renal cortical interstitium in MG.Interstitial infiltration of CD45+or CCR7+cells appeared in the 4th week,reached a maximum in the 7th week(P<0.01)and gradually decreased afterward.Conclusions Fibrocytes may be involved in the earlier stage of kidney fibrosis.The immigration of this population from peripheral blood to renal lesion site is possible to be associated with CCR7protein.
