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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 study the effects of Rehmannia glutinosa extract on renal function and glomerulosclerosis in rats with adriamycin nephrosis and to explore its possible mechanism. Methods Fifty SD male rats were randomly divided into groups according to body weight: 1. Normal control group (group C: 10): a single dose of 9 g · L-1 saline was injected through the tail vein; 2. The model group (40 Only): a single injection of doxorubicin in the tail vein of the rat, 7.5mg · kg-1 modeling, 2 weeks after 24h urine for urinary protein quantitative detection, 24h urinary protein quantitative> 30mg for the kidney disease model was established, Achieved 35 standards. Then the model group was randomly divided into kidney disease model control group (M group, 18), Rehmannia extract group (D group, 17). Group D was given 2kg · L-1 Rehmanniae Radix extract (10g · kg-1) 2 weeks after the model was established. The rats in group D were given gavage once a day for 8 weeks. Groups C and M were given equal amount of 9g · L-1 saline gavage for a total of 8 weeks. The expression of MMP-2 and TIMP-2 in renal tissue was detected by immunohistochemical method. The expression of MMP-2 and TIMP-2 in renal tissue was detected by reverse transcription-polymerase chain reaction Tissue MMP-2 and TIMP-2 mRNA expression. Results At the end of the 8th week, the urinary protein excretion, cholesterol (TC), serum creatinine (Scr) and BUN in M group were significantly increased compared with those in C group, while the serum protein was significantly decreased. Compared with M group, 24h urinary protein, TC, Scr and BUN levels were significantly decreased, while the serum protein was significantly increased. The expression of MMP-2 and TIMP-2 in group D was higher than that in group M, but lower than that in group C. Conclusion Rehmanniae extract can up-regulate the expression of MMP-2 and TIMP-2 in renal tissues, regulate the imbalance of MMP-2 / TIMP-2, promote the degradation of extracellular matrix components and slow down the glomerular sclerosis of doxorubicin nephropathy rats The process.