摘要
目的 通过大黄对实验性肾硬化大鼠中细胞周期负调控蛋白p27的表达和肾小球细胞增殖的影响,探讨大黄延缓肾硬化进展的作用机制。方法 3个月龄雄性Wistar大鼠 24只,随机分为对照组、肾硬化组和治疗组,每组8只。肾硬化组大鼠在无菌条件下行左肾摘除,术后第 7天给予多柔比星 5mg·kg 1,尾部静脉注射,再于术后第 28天重复注射多柔比星 3mg·kg 1。治疗组处理同肾硬化组,并于肾摘除当天开始每日灌服大黄抽提液(溶于 10%纤维素钠溶液)0 5mg·kg 1,对照组大鼠则分别以假手术和静脉注射等体积 0 9%氯化钠注射液替代。3组于手术或假手术后第13周处死大鼠。测定各组大鼠血尿素氮(BUN)、血肌酐(SCr)、24h尿蛋白定量以及肾小球平均截面积和平均体积。分离肾小球,提取肾小球总RNA,用半定量RT PCR方法检测肾小球内增殖细胞核抗原 (PCNA)mRNA的表达,同时采取免疫组织化学方法检测PCNA和细胞周期负调控蛋白p27的表达。结果 治疗组血尿素氮、血肌酐和 24h尿蛋白均较肾硬化组明显降低(P<0 05或P<0 01)。组织病理学检查显示治疗组病理损害明显减轻,肾小球截面积和平均体积明显减小。与肾硬化组比较,治疗组肾小球PCNAmRNA表达明显减弱,增殖指数下降,p27蛋白表达升高 (P<0 01)。
Objective To study the effect of rhubarb extract on the expression of cycline kinase inhibitor p27 and glomerular cell proliferation in experimental murine glomerulosclerosis, so as to probe into the mechanism of rhubarb in retarding the progress of glomerulosclerosis. Methods 24 adult male Wistar rats were randomly divided into 3 equal groups: the control group, the glomerulosclerosis group and test group. Rats of the glomerulosclerosis group were submitted to extirpation of the left kidney under aseptic condition. 7 days later these rats were given each an IV injection of 5 mg·kg 1 of doxorubicin. 28 days after the operation, each of these rats received another IV injection of 3 mg·kg 1 of doxorubicin. Rats of the test group were subjected to the same operation and the same IV injections as the animals of the glomerulosclerosis group. In addition, rats of the test group were given each by gastrogavage 0.5 mg·kg 1 of rhubarb extract dissolved in 10% sodium cellulose, q.d., beginning from the day of operation .Rats of the control group were submitted to sham operation and received equivalent volumes of 0.9% sodium chloride solution by gastrogavage as well. 13 weeks after the operation or sham operation, 24 h urine specimen of each animal was collected and all rats of the 3 groups were then sacrificed. Blood urea nitrogen(BUN), serum creatinine(SCr) ,quantity of 24 h urine protein, profile of the average area( A G )and volume( V G )of the glomerulus were determined. Glomeruli were separated and the total RNAs extracted. Expression of PCNA(proliferation cell nuclear antigen) mRNA on the glomeruli was assayed with RT PCR while the expression of PCNA and cycline kinase inhibitor p27 in the glomeruli was detected with immunohistochemical methods. Results Levels of BUN and SCr were much lower and amounts of 24 h urinary protein much smaller in rats of the test group than those of the glomerulosclerosis group( P <0.05 or P <0.01). Histopathological examination revealed t
出处
《医药导报》
CAS
2005年第4期278-281,共4页
Herald of Medicine
