摘要
目的研究地黄提取物对多柔比星肾病大鼠肾功能和肾小球硬化的影响,探讨其可能作用机制。方法 50只SD雄性大鼠,按体质量大小随机分组:1.正常对照组(C组,10只):采用一次性经尾静脉注射等量9g·L-1盐水;2.模型组(40只):大鼠尾静脉内一次性注射多柔比星,7.5mg·kg-1造模,2周后留取24h尿液进行尿蛋白定量检测,24h尿蛋白定量>30mg为肾病模型成立,达到标准35只。随后将模型组随机分为肾病模型对照组(M组,18只)、地黄提取物组(D组,17只)。D组于造模2周后开始予2kg·L-1地黄提取物(10g·kg-1),每日1次灌胃,共8周;C组和M组2周后每天予等量的9g·L-1盐水灌胃,共8周。采用免疫组织化学法检测其肾组织基质金属蛋白酶-2(MMP-2)及基质金属蛋白酶组织抑制因子-2(TIMP-2)蛋白的表达变化,反转录(RT)-PCR法检测其肾组织MMP-2和TIMP-2 mRNA表达。结果实验8周末,与C组比较,M组大鼠24h尿蛋白定量、胆固醇(TC)、血肌酐(Scr)和BUN水平均显著上升,而血清蛋白则显著降低;与M组比较,D组大鼠24h尿蛋白定量、TC、Scr和BUN水平均显著下降,而血清蛋白则显著升高。D组MMP-2及TIMP-2的表达高于M组,但低于C组。结论地黄提取物可上调肾组织MMP-2、TIMP-2的表达,调节MMP-2/TIMP-2的比例失衡,促进细胞外基质成分的降解,减缓多柔比星肾病大鼠肾小球硬化的进程。
Objective To evaluate the effect of rehmannia glutinosa extract on the pathogenesis of adriamycin - induced nephropathy and its mechanism. Methods Fifty male Sprague - Dawlay rats were randomly divided into 2 groups,including normal control group（n = 10, group C） ,and model group（n = 40）. The rats model of nephropathy was established by tail vein injection of adriamycin 7.5 mg·kg^-1. The normal control group was established by tail vein injection of physiological saline equally. After 2 weeks,if the urine protein was more than 30 mg in 24 hours,then the adriamycin nephrotic model was successful. The adriamycin nephrotic rats（35 rats）were divided randomly into model group of adriamycin - imlueed nephropathy（ n = 18 ,group M） and the group treated with rehmannia glutinosa extract（ n = 17 ,group D）. Then group C and group M were intragastrically fed with physiological saline,while the rats in the group D were intragastrically fed with rehmannia glutinosa extract （ 10 g · kg^-1 ）. The total time was 8 weeks. The expressions of matrix metalloproteinases - 2 （ MMP - 2 ） and tissue inhibitor of metalloproteinase -2 （TIMP- 2） in the cortex of the kidneys were examined by using immunohistochemistry and reverse transcription -poly- merase chain reaction （ RT - PCR） technique. Results On the 56~ day,colupared with group C,24 h urinary protein excretion, total cholesterol,serum creatinine and blood urea nitrogen increased significantly in group M,while albumin decreased significantly in group M;Mean- while, compared with group M, after 8 weeks with rehmannia glutinosa extract,24 h urinary, protein excretion, total cholesterol, serum creatinine and blood urea nitrogen decreased significantly in group D,but albumin increased significantly in group D. Compared with group M,protein ex- pression levels of MMP - 2 and TIMP - 2 increased significantly in group D. Compared with group C, protein expression levels of MMP - 2 and TIMP-2 descreased significantly in group D. Conclusions Rehmannia glutinosa extract offers a protective effect on adriamycin nephrotic rats. It possibly increase the expressions of MMP - 2 and TIMP - 2. The disproportion of MMP - 2/TIMP - 2, which result in the increased degradation of extracellular matrix may contribute to the development of glomerularsclerosis.
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2010年第23期1815-1818,共4页
Journal of Applied Clinical Pediatrics
基金
浙江省教育厅基金(20061807)
