机构地区:[1]河南中医药大学药学院,郑州450046 [2]呼吸疾病诊疗与新药研发河南省协同创新中心,郑州450046 [3]河南中医药大学第一附属医院,郑州450000 [4]黑龙江中医药大学,哈尔滨150040
出 处:《中国实验方剂学杂志》2016年第23期103-110,共8页Chinese Journal of Experimental Traditional Medical Formulae
基 金:国家重点基础研究发展计划(973计划)项目(2013CB531802)
摘 要:目的:探讨桑白皮各化学拆分组分对阿霉素肾病大鼠水钠潴留的影响及其作用机制。方法:采用一次性尾静脉注射阿霉素(6.5 mg·kg^(-1))建立阿霉素肾病模型,造模7 d后开始ig给药,连续给药21 d。实验期间于第7,14,21,28天留取尿液,检测大鼠尿量,24 h尿蛋白,尿钠及尿渗透压。给药3周后,测定各组大鼠血液渗透压、电解质及血液中总胆固醇(TC),甘油三酯(TG),白蛋白(ALB),尿素氮(BUN),肌酐(Cr),抗利尿激素(AVP)的含量,同时计算肾脏指数,并检测肾脏中抗利尿激素V2受体(AVPV2R),水通道蛋白-2(AQP2)的水平及Na+-K+-ATP酶的活性等指标,蛋白免疫印迹法(Western bolt)检测肾脏AQP2的表达。结果:桑白皮水煎液能够降低阿霉素肾病大鼠的尿蛋白含量,改善低蛋白血症与高脂血症,并且以低剂量(476 mg·kg^(-1))效果最好;各化学拆分组分中桑白皮30%乙醇洗脱组分能够显著降低阿霉素肾病大鼠24 h尿蛋白,TC,TG,AVP,AVPV2R,AQP2含量,降低Na+-K+-ATP酶活性及肾脏指数(P<0.05,P<0.01),能够明显增加阿霉素肾病大鼠ALB,尿量,尿钠及尿渗透压(P<0.05,P<0.01)。结论:桑白皮水煎液能够显著改善阿霉素肾病大鼠的各项病理症状,其30%乙醇洗脱组分为最佳有效部位,且其改善阿霉素肾病大鼠水钠潴留的机制可能与调节血浆AVP,肾脏AVPV2R,AQP2表达及Na+-K+-ATP酶活性有关。Objective: To observe the effects of chemical splitting fractions of Mori Cortex on water sodium retention in rats with Adriamycin-induced nephrotic syndrome and explore its mechanism. Method: The adriamycin nephropathy models were established by single tranvenous injection of adriamycin( dosage 6. 5mg·kg-1). The drugs were used continuously for 21 days from the 7thday. On days 7,14,21 and 28,urine output,24 h urine protein,urinary sodium and urinary osmolality of these rats were detected. After 3 weeks of drug administration,plasma osmolality,plasma electrolyte,total cholesterol( TC),triglycerides( TG),albumin( ALB),blood urea nitrogen( BUN),serum creatinine( Cr),and antidiuretic hormone( AVP) levels were detected,and the kidney index was calculated,antidiuretic hormone receptor 2( AVPV2R),aquaporin-2( AQP2)levels in kidney and Na+-K+-ATPase activity were detected as well. At last,the expression level of AQP2 in kidney was detected by Western bolt. Result: Mori Cortex water decoction could down-regulate the level of 24 h urinary protein,improve hypoalbuminemia and hyperlipidemia,and the low dose( 476 mg·kg-1) showed the best effect,30% ethanol fraction of Mori Cortex could significantly down-regulate 24 h urinary protein,TC,TG,AVP,AVPV2 R,and AQP2 levels,decrease Na+-K+-ATPase activity and kidney index( P〈 0. 05,P〈 0. 01),and significantly up-regulate the levels of ALB,urine output,urinary sodium and urinary osmolality( P〈 0. 05,P 0. 01). Conclusion: Mori Cortex water decoction could significantly improve the pathological symptoms of rats with adriamycin-induced nephropathy,and 30% ethanol fraction is the most effective part. Its mechanism for improving water sodium retention in Adriamycin-induced nephropathy may be associated with regulating the expression levels of plasma AVP,renal AVPV2,AQP2 and Na+-K+-ATPase activity.
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