CAJ | 학술논문

目的通过观察白三烯受体拮抗剂(LTRAs,孟鲁司特钠)对多柔比星肾病(ADN)大鼠血、尿生化指标,肾脏组织病理、nephrin、podocalyxin及细胞间黏附因子1(ICAM-1)在肾组织表达的影响,探讨其在ADN大鼠中的干预作用.方法建立大鼠ADN模型,分为A组(正常对照组)、B组(ADN组)、C组(泼尼松治疗组)、D组(孟鲁司特钠治疗组)及E组(孟鲁司特钠联合泼尼松治疗组).监测实验第4周及第8周24 h尿蛋白定量(24 h-up)及血生化指标动态变化,计算内生肌酐清除率(Ccr).观察肾组织病理形态学改变及肾组织中nephrin、podocalyxin及ICAM-1的表达.结果实验第4周时尿蛋白及清蛋白指标均达到ADN模型要求,提示模型制作成功.实验第8周,与B组比较,各治疗组大鼠各项观察指标均有不同的改善,24 h-up、血胆固醇及肌酐显著降低(P＜0.05),总蛋白、清蛋白及Ccr较前增加(P＜0.05),肾组织病理改变减轻,肾脏病理积分及肾小球细胞外基质/肾小球面积比值降低(P＜0.01),肾小球及肾小管ICAM-1表达减少(P＜0.01),nephrin、podocalyxin表达增多.综合比较,其中E组疗效最好.结论 LTRAs可能通过对肾组织ICAM-1的抑制减少蛋白尿从而发挥保护肾脏的作用,与泼尼松联合应用治疗大鼠ADN可以起到协同的作用,药效明显优于两药的单独应用.
목적 통과관찰백삼희수체길항제(LTRAs,맹로사특납)대다유비성신병(ADN)대서혈、뇨생화지표,신장조직병리、nephrin、podocalyxin급세포간점부인자1(ICAM-1)재신조직표체적영향,탐토기재ADN대서중적간예작용.방법 건립대서ADN모형,분위A조(정상대조조)、B조(ADN조)、C조(발니송치료조)、D조(맹로사특납치료조)급E조(맹로사특납연합발니송치료조).감측실험제4주급제8주24 h뇨단백정량(24 h-up)급혈생화지표동태변화,계산내생기항청제솔(Ccr).관찰신조직병리형태학개변급신조직중nephrin、podocalyxin급ICAM-1적표체.결과 실험제4주시뇨단백급청단백지표균체도ADN모형요구,제시모형제작성공.실험제8주,여B조비교,각치료조대서각항관찰지표균유불동적개선,24 h-up、혈담고순급기항현저강저(P＜0.05),총단백、청단백급Ccr교전증가(P＜0.05),신조직병리개변감경,신장병리적분급신소구세포외기질/신소구면적비치강저(P＜0.01),신소구급신소관ICAM-1표체감소(P＜0.01),nephrin、podocalyxin표체증다.종합비교,기중E조료효최호.결론 LTRAs가능통과대신조직ICAM-1적억제감소단백뇨종이발휘보호신장적작용,여발니송연합응용치료대서ADN가이기도협동적작용,약효명현우우량약적단독응용.
Objective To explore the effect of leukotriene receptor antagonist (LTRAs,montelukast) on serum indicators,urine indicators,renal pathology,intercellular adhesion molecule-1 (ICAM-1),nephrin and podocalyxin on renal tissue in adriamycin(ADR)-induced nephropathy(ADN) rats.Methods ADN was induced through a tail intravenons injection of ADR.The 40 healthy male Wistar rats were randomly divided into 5 groups:group A (control group),group B(ADN group),group C(prednisone-treated group),group D(montelukast-treated group) and group E (prednisone and montelukast-treated group).Twenty-four-hour urinary protein (24 h-up) and serum index were measured serially in the 4th,8th week and the values of creatinine clearance rate(Ccr) were calculated.At the end of the 8th week,all rats were sacrificed to collect kidney tissues for microscopy observation of renal pathological changes.The expression of nephrin,podocalyxin and ICAM-1 in renal tissues were detected through immunohistochemistry method.Results Compared with group A,in the 4th week,24 h-up and albumin reached the level of ADR nephropathy model.Compared with group B,in the 8th week,24 h-up,cholesterol,serum creatinine and renal pathology changes in the 3 treated groups were significantly reduced (P ＜ 0.05),but serum total protein,albumin and Ccr significantly increased (P ＜ 0.05),while extracellular matrix/glomerulararea and renal pathology score significantly reduced (P ＜ 0.01),and ICAM-1 significantly decreased(P ＜0.01).Compared with group C and group D,expressions of nephrin and podocalyxin in group E were the highest.Besides,the curative effect of integrated treatment was better than other treatments.Conclusions Maybe through inhibition of ICAM-1,LTRAs had a protective effect on renal tissue.The integrated treatment of LTRAs with prednisone has a synergistic effect and drug effect is superior to any drug alone in ADN.