摘要
近年在全球陸續發生由中草藥引起之腎病變，其中最主要的原因之ㄧ是由於誤用含有馬兜鈴酸成分的中草藥，而引起馬兜鈴酸腎病變（nephropathy of aristolochic acid）。其腎臟病理特徵為近位端腎小管瀰漫性萎縮、寡細胞性質的細胞浸潤與細胞間隙纖維化，而腎絲球體則相對無損傷。本實驗期望利用單次投予不同劑量或是藉由不同給藥途徑投予馬兜鈴酸至家兔體內，藉由觀察兔子病理組織與腎功能生化值的變化，了解馬兜鈴酸的腎毒性作用。 馬兜鈴酸以單次靜脈投予0.25、0.5、1.0、2.0 mg/kg以及口服投予1.0 mg/kg至家兔體內，投藥後每天監測家兔血漿肌氨酸酐以及血清N-acetyl-beta-D-glucosaminidase（NAG）濃度變化，並且定期犧牲兔子取其腎臟製作組織切片，以供鏡檢；之後將馬兜鈴酸0.25 mg/kg以單次靜脈投予至另一批家兔体內，延長觀察期以了解受損後的腎小管有無再生的可能性。 投予馬兜鈴酸之後，不論投予劑量高低，血漿肌氨酸酐濃度都立即上升。血漿肌氨酸酐與血清NAG監測結果顯示靜脈投予馬兜鈴酸0.25 mg/kg以及口服投予1.0 mg/kg後腎功能只有輕微損傷，而其他投予劑量對於腎功能造成顯著的影響。血清NAG濃度變化不如血漿肌氨酸酐明顯，血清NAG並不適合用於腎病變的監測。 組織切片結果顯示所有馬兜鈴酸投予劑量皆造成腎小管萎縮，在高劑量可觀察到腎小管壞死；投予低劑量馬兜鈴酸之後本實驗並沒有觀察到損傷的腎小管有再生的現象；腎絲球體在所有投予劑量皆相對正常。 將血漿肌氨酸酐、血清NAG濃度與腎組織損傷量化結果進行相關性評估，結果顯示腎臟損傷嚴重時，腎功能生化監測結果與腎組織損傷量化結果有良好相關性。靜脈投予2.0 mg/kg馬兜鈴酸後腎功能生化監測結果與腎組織損傷量化結果呈現顯著正相關（P < 0.05）；在其他投予劑量可以觀察到隨著血漿肌氨酸酐濃度上升，腎組織損傷程度逐漸加重。整體而言，馬兜鈴酸腎毒性與投予劑量呈顯著正相關（P＜0.05）。
並列摘要
Chinese herbs induced nephrotoxicity has spread worldwide recently. Inadvertly misuse of the Chinese herbs, which contain aristolochic acids （AA）, is the main cause of the nephropathy. Aristolochic acid nephropathy （AAN）is characterized by its extensive tubular atrophy with rare cell infiltration and interstitial fibrosis while glomeruli are relatively spared. In the present study, renal toxic effects of AA of various doses or different routes were evaluated through renal histology and function in rabbits. AA was intravenously injected (IV) into rabbits with various doses：0.25, 0.5, 1.0 and 2.0 mg/kg to rabbits. AA was also given orally （PO）with 1.0 mg/kg to rabbits. After dosing, rabbits were under monitoring of plasma creatinine, serum N-acetyl-beta-D-glucosaminidase（NAG）activity and sacrificed on different days for the histological examination. After the previous study, AA 0.25 mg/kg was administrated intravenously again to understand the possibility of tubular regeneration after AA intoxication. Plasma creatinine increased immediately after AA treatment in all conditions. The results of plasma creatinine and serum NAG monitoring indicated that renal function was changed slightly after IV 0.25 mg/kg and PO 1.0 mg/kg AA while higher doses of aristolochic acid had greater impacts on renal function. Serum NAG was less sensitive than plasma creatinine and not suitable for monitoring renal function. Histologically, tubular atrophy was significant in all conditions and AA developed widespread tubular necrosis in higher doses. There was no remarkable evidence of tubular regeneration observed in this study. The glomeruli were relatively spared. There were good relationships between biochemistry and tubulointerstitial histological scores（TIHS）when renal was impaired severely. After 2.0 mg/kg AA intoxication, biochemistry correlated tightly with tubulointerstitial scores was observed （P < 0.05）.In other doses, the elevations of plasma creatinine levels were followed by higher THIS. In conclusions, the renal toxic effects of AA were significantly dose-dependent（P < 0.05）.
參考文獻
延伸閱讀
- 范美玉（2006）。馬兜鈴酸在家兔體內之藥物動力學與腎毒性研究〔碩士論文，臺北醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0007-1704200715050566
- 張皓傑（2000）。Isoferulic acid 在家兔體內之藥物動力學研究〔碩士論文，臺北醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0007-1704200714450504
- 張馨慧（1996）。Sulfadiazine 在慢速乙醯反應型家兔體內之藥物動力學研究〔碩士論文，臺北醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0007-1704200714395324
- 郭釗麟（2000）。Diphenidol在家兔體內代謝之研究〔碩士論文，臺北醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0007-1704200714450506
- 王郁婷、朱宗信（2004）。Heroin-associated Nephropathy。台灣醫學，8(5)，735-737。https://doi.org/10.6320/FJM.2004.8(5).21