摘要
目的 在慢性嘌呤霉素肾病 (PAN)大鼠模型中观察黄芪当归合剂 (A&A)对肾脏固有细胞表型及MAPK信号通路各亚类激酶 (ERK、JNK和p38)表达与活性的影响 ,初步探讨A&A治疗作用的细胞生物学机制。方法 肾组织标本来源于对照组、PAN组、A&A组和ACEI组大鼠。采用常规病理染色和免疫组化技术 ,观察各组肾组织不同部位的病理改变、细胞数量、细胞外基质积聚程度、不同部位α SMA表达变化及肾组织内MAPK表达及活化情况。结果 PAN大鼠肾小球内的α SMA表达量与肾小球系膜细胞增殖、细胞外基质的积聚程度密切相关 ;肾小管间质区的α SMA表达量与肾间质浸润细胞数相关 ,同时伴有肾小管上皮变性、萎缩和扩张。A&A治疗可使PAN大鼠上述部位的α SMA表达和病理变化明显减轻。在本实验条件下 ,PAN组与对照组肾组织内JNK、ERK、p38的蛋白表达量及表达部位无差别 ,肾组织内ERK、p38亦未被激活 ;PAN大鼠肾小球、肾小管及肾间质细胞的JNK均明显活化 ,A&A可明显抑制上述部位的JNK活化。结论 黄芪当归合剂可显著减轻嘌呤霉素肾病的肾脏损伤 ,它对肾脏固有细胞 (尤其是系膜细胞 )表型转化的抑制作用可能是其作用的主要环节之一 。
AIM A&A treated PAN rats, and to observe the effects of A&A on MAPK signaling pathway. METHODS Rats were divided into control, PAN, A&A treated PAN (A&A) and enapril treated PAN (ACEI) groups. The pathological lesion was observed under a light microscope. Immunohistochemistry combined with semi quantitive method was used to investigate the following parameters: cell number, α SMA expression and extracellular matrix deposition. Expression and phosphorylation of protein kinases ERK, JNK and p38 were assayed. RESULTS In PAN rats, A&A suppressed α SMA expression, which was closely correlated to cell proliferation, and extracellular matrix accumulation in glomerular mesangium. A&A significantly attenuated α SMA expression in the tubulo interstitial area which was also parallel to the renal interstitial fibrosis.In this study, expression of all subtypes of MAPK had no difference between control and PAN groups. Compared with the inactivation of ERK and p38, phosphorylation of JNK was observed in glomeruli, renal tubules and interstitial cells in PAN rats, which was also inhibited by A&A treatment. CONCLUSION The inhibitory effect of A&A on phenotypic changes of renal resident cells, especially glomerular mesangial cell, may participate in its renal protective mechanisms. This effect, at least partially, was mediated by down regulated JNK activation.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2003年第9期1069-1074,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助课题 No 3 0 2 71695
北京大学"创建世界一流大学工程"基金资助课题
