心肝宝胶囊对阿霉素肾病大鼠的肾脏保护作用

作者	单位
甄军晖	山东大学医学院病理科
王娜	山东大学齐鲁医院肾内科
亓敏	山东大学齐鲁医院肾内科
刘茂静	山东大学齐鲁医院肾内科
梁素忍	山东大学医学院病理科
胡昭	山东大学齐鲁医院肾内科
冯进波	山东大学医学院病理科

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中文摘要:

目的研究心肝宝胶囊对阿霉素肾病大鼠的肾脏保护作用。方法雄性SD大鼠40只,随机分为正常对照组、阿霉素肾病模型组(模型组)、贝那普利组、心肝宝胶囊组(心肝宝组)。采用左侧肾脏切除加尾静脉重复注射阿霉素的方法建立阿霉素肾病模型。术后1周心肝宝组给予心肝宝胶囊500mg/(kg·d)灌胃,贝那普利组给予贝那普利4mg/(kg·d)灌胃。用药第8周后观察各组大鼠24h尿蛋白定量、血生化,取肾组织于光镜、电镜下观察肾脏病理变化,应用免疫组化方法测定肾组织纤维连接蛋白(FN)、胶原-Ⅳ(COL-Ⅳ)、骨调素(OPN)的表达,采用荧光定量RT-PCR测量肾组织分子生物学指标相对表达值。结果心肝宝组24h尿蛋白定量、尿素氮、血肌酐、血脂较模型组明显降低;肾小球系膜基质比心肝宝组较模型组明显减少;肾组织的FN、COL-Ⅳ、OPN表达心肝宝组较模型组明显减少;同样,肾组织转化生长因子-β1(TGF-β1)、金属蛋白酶组织抑制剂-1(TIMP-1)及PAI-1mRNA的表达明显减少。结论心肝宝胶囊对阿霉素肾病模型,能发挥肾脏保护作用,可能是通过减少蛋白尿的排泄,纠正脂代谢紊乱,抑制细胞外基质的过度积聚,减少致纤维化因子的表达,改善肾脏病理损害而实现的。

英文摘要:

Objective To study the renal protective effect of Xinganbao Capsule on rats with adriamycin induced nephropathy (AIN). Methods Forty male SD rats were randomly divided into four groups,i.e. the normal control group (N),the AIN model group (M),the Benazepril group (B),and the Xinganbao Capsule group (X). AIN rat model was established by left unilateral nephrectomy and repeated caudal vein injection of adriamycin. Gastric perfusion of Xinganbao Capsule (at the dose of 500 mg/kg per day) and Benazepril (at the dose of 4 mg/kg per day) was given to rats in the X group and the B group respectively one week after nephrectomy. Rats were sacrificed at the 8th week after medication. The 24-h urinary protein excretion (24 h-UP) and blood biochemical indices were determined. Renal tissues were collected for pathological changes under light and electron microscopes. Expressions of fibronection (FN),collagen Ⅳ (COL-Ⅳ),and osteopont (OPN) in renal tissues were detected by immunohistochemistry. mRNA levels of transforming growth factor-beta 1 (TGF-β1),tissue inhibitor of metalloproteinase-1 (TIMP-1),and plasminogen activator inhibitor-1 (PAI-1) were measured by fluorescent Real-time PCR. Results When compared with the model group,24 h-UP,blood urea nitrogen (BUN),and serum creatinine (SCr),and blood lipids levels were significantly lowered in the X group. The mesengial matrix percentage was less in the X group than in the M group. Renal FN,COL-Ⅳ,and OPN expressions more significantly decreased in the X group than in the M group. Similarly mRNA expressions of TGF-β1,TIMP-1,PAI-1 in renal tissues obviously decreased. Conclusion Xinganbao Capsule could exert its renal protective action possibly through reducing the urinary protein excretion,correcting lipid metabolic disturbance,inhibiting excessive accumulation of extracellular matrix,decreasing the expression of fibrosis factors,and improving the pathological damage of kidneys in the AIN rat model.

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