肾炎消白方对阿霉素肾病大鼠蛋白尿的影响
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摘要
目的:探讨肾炎消白方减少阿霉素肾病大鼠蛋白尿的作用,并从生化、分子生物学角度探讨其作用机理,为临床应用提供理论依据。
方法:用尾静脉一次性注射阿霉素制备肾炎蛋白尿模型,分为5组,分别为空白对照组、模型对照组、洛汀新组、肾炎消白方低剂量组、肾炎消白方高剂量组,观察7周,检测大鼠的尿肌酐、血清BUN、Scr、Alb,ELISA法检测尿β_2-MG、尿白蛋白,免疫组化检测大鼠肾脏COL-Ⅳ、LN平均面密度比,RT-PCR检测大鼠肾组织Nephrin mRNA、CD2AP mRNA的表达。
结果:实验7周末各治疗组(肾炎消白方高、低剂量组及洛汀新组)阿霉素肾病大鼠尿白蛋白/尿肌酐值下降,以肾炎消白方高剂量组最为明显(P＜0.05);尿β_2-MG的含量降低,以肾炎消白方高剂量组最为明显(P＜0.05);血清白蛋白含量上升,以肾炎消白方高剂量组最为明显(P＜0.05);COL-Ⅳ、LN在肾组织中的表达减少,以肾炎消白方高剂量组最为明显(P＜0.05);Nephrin mRNA、CD2AP mRNA在肾组织中的表达降低,以肾炎消白方高剂量组最好;肾功能无影响(P＞0.05)。
结论:肾炎消白方能够在一定程度上减少阿霉素肾病大鼠尿蛋白的排泄量;减少阿霉素肾病大鼠尿β_2-MG的含量,对肾小管有保护作用;提高阿霉素肾病大鼠血清白蛋白的含量,其机制可能是减少尿中蛋白排泄量;降低于阿霉素肾病大鼠COL-Ⅳ、LN在肾组织中的表达,对肾脏纤维化有治疗作用;改善阿霉素肾病大鼠足细胞的形态,降低阿霉素肾病大鼠肾组织中Nephrin mRNA、CD2AP mRNA表达,对于受损足细胞有修复作用,从而减少尿蛋白的排泄量;中药高剂量组对于上述作用较中药低剂量组、洛汀新组疗效较好。
Objective:To test if nephritis Xiaobaifang decreases proteinuria level in experimental animals and investigate its mechanism by biochemical and molecular biological analysis to provide the basis for its clinical application.
Methods:We utilized a rat model in which nephritis is induced by one-time tail vein injection of doxorubicin.Animals were divided into five groups,namely the naive control group,model control group,Lotensin group,low-dose nephritis Xiaobaifang group and high-dose nephritis Xiaobaifang group.Seven weeks after treatment,we detected rat urine creatinine,serum BUN,Scr,Alb,urineβ_2-MG(by ELISA),proteinuria, COL-Ⅳand LN expression in kidney(by immunohistochemical staining), and nephrin mRNA and CD2AP mRNA expression in kidney tissue(by RT-PCR).
Results:At the end of 7-week observation,the ratio of proteinuria / urine creatinine values(P＜0.05)were reduced in animals from all treatment group with doxorubicin-induced nephritis,and the high-dose nephritis Xiaobaifang treatment had the most significant effects(P＜0.05);the urineβ_2-MG level(P＜0.05)was also decreased in all treatment group,and the high-dose nephritis Xiaobaifang treatment had the most significant effects (P＜0.05);the serum albumin concentration(P＜0.05)was increased in all treatment group;and high-dose nephritis Xiaobaifang treatment had the most significant effects(P＜0.05);the expression of both COL-Ⅳand LN in the kidney were decreased in all treatment group(P＜0.05),and the high-dose nephritis Xiaobaifang treatment had the most significant effects (P＜0.05);the treatment by nephritis Xiaobaifang did not affect the kidney function in rats with nephritis(P＞0.05);the expression of both COL-Ⅳand LN in the kidney tissue were decreased in all treatment group(P＜0.05), and the high-dose nephritis Xiaobaifang treatment had the most significant effects(P＜0.05);all animals in the treatment group had attenuated foot cell damage,lower nephrin mRNA and CD2AP mRNA expression in kidney tissues,and the high-dose nephritis Xiaobaifang treatment had the most significant effects(P＜0.05).
Conclusion:nephritis Xiaobaifang can reduce excretion a certain extent, decrease urineβ_2-MG level in nephrotic rats and protect tubulo;It can possibly increase serum albumin level by reducing excretion;It can attenuate COL-Ⅳand LN expression in kidney tissues,so it can treat kidney fibrosis;It can improve the foot cell morphology of nephrotic rats, by which it reduced excretion;It can reduce nephrin mRNA and CD2AP mRNA expression in kidney tissues from rats with doxorubicin-induced nephritis,repair injured foot cell,then.reduce excretion.The therapeutic effects with high-dose nephritis Xiaobaifang are better than low-dose nephritis Xiaobaifang or Lotensin.
方法:用尾静脉一次性注射阿霉素制备肾炎蛋白尿模型,分为5组,分别为空白对照组、模型对照组、洛汀新组、肾炎消白方低剂量组、肾炎消白方高剂量组,观察7周,检测大鼠的尿肌酐、血清BUN、Scr、Alb,ELISA法检测尿β_2-MG、尿白蛋白,免疫组化检测大鼠肾脏COL-Ⅳ、LN平均面密度比,RT-PCR检测大鼠肾组织Nephrin mRNA、CD2AP mRNA的表达。
结果:实验7周末各治疗组(肾炎消白方高、低剂量组及洛汀新组)阿霉素肾病大鼠尿白蛋白/尿肌酐值下降,以肾炎消白方高剂量组最为明显(P＜0.05);尿β_2-MG的含量降低,以肾炎消白方高剂量组最为明显(P＜0.05);血清白蛋白含量上升,以肾炎消白方高剂量组最为明显(P＜0.05);COL-Ⅳ、LN在肾组织中的表达减少,以肾炎消白方高剂量组最为明显(P＜0.05);Nephrin mRNA、CD2AP mRNA在肾组织中的表达降低,以肾炎消白方高剂量组最好;肾功能无影响(P＞0.05)。
结论:肾炎消白方能够在一定程度上减少阿霉素肾病大鼠尿蛋白的排泄量;减少阿霉素肾病大鼠尿β_2-MG的含量,对肾小管有保护作用;提高阿霉素肾病大鼠血清白蛋白的含量,其机制可能是减少尿中蛋白排泄量;降低于阿霉素肾病大鼠COL-Ⅳ、LN在肾组织中的表达,对肾脏纤维化有治疗作用;改善阿霉素肾病大鼠足细胞的形态,降低阿霉素肾病大鼠肾组织中Nephrin mRNA、CD2AP mRNA表达,对于受损足细胞有修复作用,从而减少尿蛋白的排泄量;中药高剂量组对于上述作用较中药低剂量组、洛汀新组疗效较好。
Objective:To test if nephritis Xiaobaifang decreases proteinuria level in experimental animals and investigate its mechanism by biochemical and molecular biological analysis to provide the basis for its clinical application.
Methods:We utilized a rat model in which nephritis is induced by one-time tail vein injection of doxorubicin.Animals were divided into five groups,namely the naive control group,model control group,Lotensin group,low-dose nephritis Xiaobaifang group and high-dose nephritis Xiaobaifang group.Seven weeks after treatment,we detected rat urine creatinine,serum BUN,Scr,Alb,urineβ_2-MG(by ELISA),proteinuria, COL-Ⅳand LN expression in kidney(by immunohistochemical staining), and nephrin mRNA and CD2AP mRNA expression in kidney tissue(by RT-PCR).
Results:At the end of 7-week observation,the ratio of proteinuria / urine creatinine values(P＜0.05)were reduced in animals from all treatment group with doxorubicin-induced nephritis,and the high-dose nephritis Xiaobaifang treatment had the most significant effects(P＜0.05);the urineβ_2-MG level(P＜0.05)was also decreased in all treatment group,and the high-dose nephritis Xiaobaifang treatment had the most significant effects (P＜0.05);the serum albumin concentration(P＜0.05)was increased in all treatment group;and high-dose nephritis Xiaobaifang treatment had the most significant effects(P＜0.05);the expression of both COL-Ⅳand LN in the kidney were decreased in all treatment group(P＜0.05),and the high-dose nephritis Xiaobaifang treatment had the most significant effects (P＜0.05);the treatment by nephritis Xiaobaifang did not affect the kidney function in rats with nephritis(P＞0.05);the expression of both COL-Ⅳand LN in the kidney tissue were decreased in all treatment group(P＜0.05), and the high-dose nephritis Xiaobaifang treatment had the most significant effects(P＜0.05);all animals in the treatment group had attenuated foot cell damage,lower nephrin mRNA and CD2AP mRNA expression in kidney tissues,and the high-dose nephritis Xiaobaifang treatment had the most significant effects(P＜0.05).
Conclusion:nephritis Xiaobaifang can reduce excretion a certain extent, decrease urineβ_2-MG level in nephrotic rats and protect tubulo;It can possibly increase serum albumin level by reducing excretion;It can attenuate COL-Ⅳand LN expression in kidney tissues,so it can treat kidney fibrosis;It can improve the foot cell morphology of nephrotic rats, by which it reduced excretion;It can reduce nephrin mRNA and CD2AP mRNA expression in kidney tissues from rats with doxorubicin-induced nephritis,repair injured foot cell,then.reduce excretion.The therapeutic effects with high-dose nephritis Xiaobaifang are better than low-dose nephritis Xiaobaifang or Lotensin.
引文
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