苦参碱对大鼠慢性环孢素肾毒性的保护作用的实验研究

目的 探讨苦参碱对大鼠慢性环孢素A(CsA)肾毒性是否具有保护作用及其可能机制.方法 采用大鼠慢性CsA肾毒性模型,将56只SD大鼠随机分为对照组、CsA模型组(CsA 20 mg/kg)、安博维组(安搏维10 mg/kg CsA 20 mg/kg)和苦参碱组(Matrine 100 mg/kg CsA 20 mg/kg),经胃管灌胃,每天1次,实验共4周.于第2周和第4周末两次采集血尿标本进行生化检测,肾组织行常规病理检查和免疫组化检测骨桥蛋白(OPN)、Ectodermal Dysplasia 1(ED-1)表达.结果 与对照组比较,CsA组24 h尿量、小管间质损伤评分、OPN表达和ED-1阳性细胞计数均增加,内生肌酐清除率(Ccr)下降(P均＜0.05).与CsA组相比,苦参碱能下调OPN表达,减少ED-1阳性细胞在肾组织的浸润,减轻肾脏病理改变(P＜0.05).结论 苦参碱对实验性大鼠慢性CsA肾毒性具有一定的保护作用.

Experiment Research on Preventive Effect of Matrine on Rat Chronic Nephrotoxicity Induced by Cyclosporin A

OBJECTIVE: To investigate the renal protective effect and possible mechanism of matrine on experimental cyclosporine A (CsA) induced chronic nephrotoxicity. METHODS: 56 male Sprague-Dawley rats were randomly divided into four groups: control group (olive oil 0. 2 mL/d), CsA group (CsA 20 mg/(kg x d)), Irbesartan group CCsA 20 mg/(kg x d) plus Irbesartan 10 mg/(kg x d)), matrine group CCsA 20 mg/(kg * d) plus matrine 100 mg/(kg x d)), and each group comprised fourteen rats. After treated with drugs, rats were sacrificed at the end of week 2 and 4. The body weight, 24-hours urine and blood sample were collected before rats sacrificed. The rat kidneys were taken and fixed in 10% neutral formaldehyde for HE staining. The osteopontin (OPN) and ectodermal dysplasia 1 (ED-1) were determined by immunohistochemical method. RESULTS Compared to control group, the 24-hour urine of rats, histological scores, the expression of OPN and the ED-1 positive cells number of CsA group were significantly increased, but Ccr was significantly lower (P<0. 05). Matrine could down-regulate OPN expression and decrease ED-1 positive cell infiltration in kidney, compared with CsA group (P <0. 05). CONCLUSION: Matrine has a renal protective effect on chronic cyclosporine nephrotoxicity of rat model.