摘要
目的 观察川芎嗪对阿霉素肾病肾小管间质损伤的影响,并探讨其可能的机制.方法 雄性SD大鼠40只,按简单随机法分为假手术组、模型组、川芎嗪组及苯那普利组,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.检测各组大鼠在阿霉素注射前（0周末）,用药2周末、4周末、6周末24h尿蛋白量；观察用药6周末各组大鼠肾功能指标及光镜下肾脏的病理改变,应用免疫组化方法测定肾小管间质内皮素-1（Endothelin-1 ET-1）的表达.结果 模型组24h尿蛋白量[（30.07±2.12） mg/24 h、（201.83 ±8.63） mg/24 h、（470.70 ±58.79） mg/24 h]（用药2周末、4周末、6周末）、血尿素氮[ （20.20 ±2.65） mmol/L]、肌酐[（86.79 ±2.20） μmol/L]水平、肾小管间质的损伤PAS评分（4.38 ±0.26）及ET-1表达（126.92 ±3.63）均显著高于假手术组[分别为（6.75±2.07） mg/24 h、（8.28±0.71 ）mg/24 h、（25.37±4.30） mg/24 h、（8.93±1.05） mmol/L、（49.00±5.34） μmol/L、1.06±0.19、32.09±3.71；P＜0.01]；川芎嗪组24h尿蛋白量[（176.93±9.20）mg/24 h、（270.45 ±60.21）mg/24 h]（4周末、6周末）、血尿素氮[（13.75 ±2.60） mmol/L]、肌酐[ （62.49 ±3.29）μmol/L]水平、肾间质小管的损伤PAS评分（2.78±0.10）及ET-1表达（57.44±4.98）均显著低于模型组（P＜0.01）.结论 川芎嗪对肾间质小管损伤有保护作用,其机制与减少尿蛋白的排泄,抑制ET-1的生成有关,从而减轻肾小管间质的炎症反应及纤维化.
Objective To investigate the effects of ligustrazine on renal tubulointerstitial injury in adriamycin nephrosis rats and its mechanism.Methods Forty male Sprague-Dawley rats were randomly divided into sham-operation group,model group,ligustrazine group and Benazepril group.The rat nephropathy model was established by adriamycin injection and unilateral nephrectomy.The 24-hour urinary protein excretion at the start,2nd,4th,6th weekends was analyzed.All rats were sacrificed at the 6th weekend,and then the renal function and the tubulointerstitial pathological injury were examined.Immunohistochemistry was used to measure the expression of ET-1.Results The 24-hour urinary protein excretion [ （30.07 ±2.12） mg/24 h,（201.83 ± 8.63 ） mg/24 h,（ 470.70 ± 58.79 ） mg/24 h ] （ at the 2th,4th,6th weekend）,blood urea nitrogen[ BUN（ 20.20 ± 2.65 ） mmol/L],serum creatinine[ Scr （ 86.79 ± 2.20 ） μmol/L）,tubulointerstitial pathological injury （4.38 ± 0.26） and the expression of ET-1 （ 126.92 ± 3.63 ）in model group were significantly higher than those in sham-operation group [ （ 6.75 ± 2.07 ） mg/24 h,（ 8.28 ± 0.71 ） mg/24h,（ 25.37 ± 4.30） mg/24 h,（ 8.93 ± 1.05 ） mmol/L,（49.00 ± 5.34 ） μmol/L,1.06 ± 0.19,32.09 ± 3.71,P 〈 0.01 ].Compared with model group,the 24-hour urinary protein excretion [ （ 176.93 ± 9.20）mg/24 h,（ 270.45 ± 60.21 ） mg/24 h） （ at the 4th,6th weekend）,BUN [ （ 13.75 ± 2.60 ） mmol/L ],Scr [ （ 62.49 ±3.29）μmol/ L ],Renal tubulointerstitial pathological injury （2.78 ± 0.10） and the expression of ET-1（57.44 ± 4.98 ） were significantly decreased in ligustrazine group（ P 〈 0.01 ）.Conclusions Ligustrazine can downregulate the expression of ET-1 and decreased urinary protein excretion,leading to reduce tubulointerstitial inflammation and fibrosis.
出处
《中国医师杂志》
CAS
2011年第12期1599-1602,共4页
Journal of Chinese Physician
基金
基金项目：湖南省卫生厅基金（B2008-060）
