慢性马兜铃酸肾病的临床特点与肾小管上皮-间充质转化  

Chronic renal tubular interstitial damage induced by Chinese herbs including aristolochia manshuriensis

作　　者：于阳[1] 张晓明[1] 李艳[1] 叶文玲[1] 李雪梅[1] 郑法雷[1] 

机构地区：[1]中国医学科学院中国协和医科大学北京协和医院肾内科,100730

出　　处：《北京医学》2012年第4期275-278,I0001,共5页Beijing Medical Journal

基　　金：北京自然基金面上项目(7042043)

摘　　要：目的探讨关木通等中药引起的慢性肾小管间质病变的临床病理特点,及对肾小管上皮-间充质转化(EMT)的可能作用。方法分析16例关木通等中药所致肾损害的临床表现、肾病理特点和肾小管上皮细胞向间充质细胞转化的情况。对10例肾活检标本进行α-平滑肌肌动蛋白(α-SMA)、波型蛋白和Ⅲ型胶原表达的检测。结果本组16例患者均在服用关木通等中药后出现肾脏病变,10例中药成分中明确含有关木通,5例就诊时已进入尿毒症期或尿毒症前期。临床表现为多饮、多尿,血压一般正常。尿常规基本无白细胞,蛋白尿较轻,尿β2微球蛋白显著升高(>3000ng/ml),贫血13例,伴肾性糖尿14例、肾小管酸中毒10例。肾活检显示以小管间质病变为主,大片肾小管萎缩或扩张,小管上皮细胞浊肿、脱落,间质灶性或成片以单核细胞为主的淋巴细胞浸润及大片纤维化,小叶间动脉壁可增厚。肾小球无病变或轻度系膜细胞增生。肾小管上皮细胞α-SMA、波型蛋白表达增加,肾间质Ⅲ型胶原表达增加。7例予泼尼松15～50mg/d治疗8～72个月后,4例肾功能有所好转,2例血肌酐(SCr)、血尿素氮(BUN)水平稳定,1例肾功能继续恶化。1例经过对症治疗2个月后肾功能正常,5年后肾小管酸中毒和肾性糖尿完全消失。结论关木通等中药可引起慢性小管间质病变,肾小管上皮细胞表型转化很可能是其重要机制之一。皮质激素可能对缓解关木通等中药所致肾小管间质病变有一定作用,其疗效尚需进一步观察。Objective To study the clinical and pathological features of patients with chronic renal tubular interstitial damage induced by Chinese herbs including aristolochia manshuriensis and the role of tubular epithelial-mesenchymal transition （EMT） in renal fibrosis of these cases. Methods Sixteen eases with herbs-induced chronic renal tubular interstitial damage were clinicopathalogically analyzed. The expression of α-SMA, vimentin and collagen III in renal tissues were examined in 10 cases by immunohistoehemistry. Results All sixteen patients had chronic renal insufficiency after intaking of Chinese herbs. Ten of them took the herbs eontaining aristolochia manshuriensis definitely. Five of them presented rapidly progressive acute renal failure. All of them had similar clinical features, such as polydipsia, polysuria, anemia, glycosuria, aciduria, elevated urine 132microglobin （132m）, and proximal tubular acidosis. The renal biopsies showed extensive hypocellular interstitial fibrosis, tubular atrophy and loss of tubules. Glomeruli were apparently intact. The expression of α-SMA and vimentin in renal tubular epithelial cells were increased, and the expression of collagen IU in renal interstitium was also increased. Conclusions Chinese herbs aristolochia manshuriensis may induce chronic renal tubular interstitial damage characterized by interstitial fibrosis, which is probably related to phenotypic transition of tubular epithelial cell. Whether steroid therapy can slow the progression of tubular interstitial damage needs to be studied further.

关 键 词：中药 关木通 肾损害 转化 

分 类 号：R692[医药卫生—泌尿科学]