摘要
目的研究关木通所含马兜铃酸(AA)对肾小管上皮凋亡及凋亡信号蛋白Caspase-3表达的影响。方法将雄性Wistar大鼠46只随机分为关木通组与对照组。关木通组按AA20mg·kg-·1d-1灌胃关木通浸膏,对照组灌胃饮用水。于用药第4、8、12周分批处死动物,取肾组织行HE、PAS、Masson染色,肾脏病理分析肾小管间质损伤程度,TUNEL法检测肾小管上皮细胞凋亡,免疫组化检测PCNA、Caspase-3表达。结果关木通组出现急性小管间质损害,随着用药时间延长,肾小管间质损害程度加重;TUNEL染色显示第4～8周时凋亡指数升高,第12周时凋亡指数下降;PCNA主要表达于损伤的肾小管,其增殖指数在第4周和第8周时显著升高,但第12周时下降;Caspases-3表达水平在8周前显著增高,主要表达在损伤小管及浸润的炎细胞,第12周时表达水平下降。对照组肾小管偶见凋亡细胞,增殖指数维持在一定水平,Caspases-3有少许表达。结论关木通所含马兜铃酸可引起肾小管损害,早期主要为肾小管损伤、凋亡,并伴随Caspase-3表达水平升高,后期则以小管坏死、萎缩和间质纤维化为特点,Caspase-3表达略下降,且肾小管再生修复能力下降。
Objective To observe the effects of aristolochic acid contained in Caulis Aristolochiae Manshuriensis on the tubular epithelial cell apoptosis and Caspases-3 expression. Methods Forty-six male Wistar rats were randomly divided into 2 groups： model group in which 26 rats were given the extracta of Caulis Aristolochiae Manshuriensis（CAM） （aristolochic acid at AA20 mg＇kg-~＇d-~） intragastrically, and control group in which 20 rats were given equal volume of potable water. At the end of 4th, 8th, 12th weeks, the kidney of each rat was sacrificed separately. HE, PAS and Masson stainings were adopted to analyze the degree of tubulo-interstitial lesion, the tubular epithelial cell apoptosis was detected by TUNEL methods. The expression of proliferate cell nuclear antigen （PCNA） and Caspase-3 were detected by the immunohistochemical method. Results The aristolochic acid in CAM could induce acute renal tubular-interstitial lesion in model group, and the lesion progressed along with feeding times. The TUNEL staining showed cell apoptosis index rose at 4 th, 8 th weeks, but declined at 12 th week. The positive expression of PCNA was seen mainly in the injured tube, the proliferate index increased at 4 th, 8 th weeks, but declined at 12 th week. The Caspase-3 expression increased before the 8th week, but decreased at 12 th week, mostly in the injured tubular cells and inflammation cells, but little expression in atrophic tubes. Conclusion The aristolochic acid in CAM can induce tubular lesion： in the early stage it is characterized by tubular injury and apoptosis, and elevated Caspase-3 expression; in late stage by tubular necrosis and atrophy, declined Caspase-3 expression and lowered tubular regeneration.
出处
《上海中医药杂志》
北大核心
2007年第11期70-73,共4页
Shanghai Journal of Traditional Chinese Medicine
基金
上海市青年科技启明星基金资助项目(04QMX1453)
作者简介
王会玲（1969-），女，陕西汉中人，博士，副主任医师，主要从事肾脏病的基础研究和临床工作。
