商陆皂甙甲对阿霉素肾小球硬化大鼠细胞外基质的影响

目的观察商陆皂甙甲(EsA)对阿霉素肾小球硬化大鼠细胞外基质的影响并探讨其可能机制。方法将48只SD大鼠随机分为假手术组、模型组、EsA组、依那普利组,模型组、EsA组、依那普利组采用单侧肾切除并尾静脉重复注射阿霉素的方法建立大鼠肾小球硬化模型,假手术组大鼠仅剥离肾脂肪包膜,不切除肾脏,术后给予等量生理盐水尾静脉注射。术后1周开始,EsA组按20 mg.kg-1.d-1给EsA腹腔注射,依那普利组按10 mg.kg-1.d-1给依那普利混悬液灌胃,假手术组和模型组给2 mL生理盐水灌胃,连续治疗93 d后处死。观察EsA对肾小球硬化大鼠24 h尿蛋白、血浆白蛋白、血肌酐(Scr)、尿素氮(BUN)含量、肾小球病理改变及肾小球Ⅳ型胶原表达的影响。结果8周、13周时,模型组、EsA组和依那普利组大鼠24 h尿蛋白均明显高于假手术组(P<0.01),但EsA组和依那普利组大鼠尿蛋白明显低于模型组(P<0.01)。处死前模型组、EsA组和依那普利组大鼠血肌酐(Scr)、尿素氮(BUN)水平较假手术组明显升高(P<0.05),血清白蛋白显著减低(P<0.05);EsA组和依那普利组与模型组比较Scr、BUN水平明显降低(P<0.01),血清白蛋白明显高于模型组(P<0.01)。模型组大鼠、EsA组、依那普利组肾小球硬化指数、Col-Ⅳ的表达均较假手术组明显增强(P<0.05),但EsA组、依那普利组肾小球硬化指数、Col-Ⅳ的表达较模型组明显减弱(P<0.01)。EsA组和依那普利组之间血清白蛋白、Scr、BUN、肾小球硬化指数、Col-Ⅳ的表达及8周和13周尿蛋白比较差别无统计学意义(P>0.05)。结论EsA可减轻肾小球硬化大鼠系膜基质中Ⅳ型胶原的过度沉积,减少尿蛋白,延缓肾小球硬化的发生、发展。

Esculentoside A on extracellular matrix of adriamycin-induced glomerulosclerosis rats

Objective To observe the effects of eseulentoside A （EsA） on extracellular matrix of adriamycin-induced glomerulosclerosis rats and to explore the possible mechanisms. Methods Forty-eight male SD rats were randomly divided into four groups：sham operation group, model group, EsA group, and enalapril group. Glomerulosclerosis rat model was established by injecting adriamycin duplicately through caudal vein and cutting unilateral kidney. The rats in sham operation group were avulsed renal fat poplos only, then the same dose of physiological saline was given through caudal vein after operation. On the subsequent days after one week operation the rats in EsA group, and enalapril group were respectively treated with EsA （20 mg ·kg^-1·d^-1 ） or enalapril（ 10 mg·kg^-1·d^-1） , sham operation group and model group were gastric-perfused with the same dose of saline for ninety-three days. Then the rats were killed. The influence of EsA on the levels of 24 h urinary protein excretion, serum albumin and serum creatinine（Scr） , urea nitrogen（BUN） , pathological changes of glomerulus and expression of Collagen-Ⅳ in glomeruli of rats with glomerulosclerosis were detected. Results At the end of 8^th, 13^th week after operation, compared with sham operation group, the levels of 24 h urinary protein excretion were higher in model group, EsA group and enalapril group（ P 〈 0.01 ） , but it was lower in EsA group and enalapril group than that in model group（ P 〈 0. 01 ） ;Before the rats were killed, the levels of Scr, BUN were higher and the levels of serum albumin were lower in model group, EsA group and enalapril group than those in sham operation group（ P 〈 0. 05 ）. Glomeruloselerosis index and the expression of Collagen-Ⅳ in glomeruli were increased more obviously in model group, EsA group and enalapril group than those in sham operation group （ P 〈 0.05 ） , but they were decreased more obviously in EsA groups and enalapril group than those in the model group（ P 〈0.01 ）. Th