Zone 203 Renal cortex Renal medulla Aorta Inferior

Zone 203

人類泌尿系統示意圖 Renal cortex Renal medulla Aorta Inferior vena cava Renal artery and vein Renal pelvis Kidney Ureter Urinary bladder Urethra A The excretory system Bowman’s capsule Arteriole from renal artery Glomerulus 1 Proximal tubule Capillaries Arteriole from glomerulus Branch of renal vein 2 Loop of Henle with capillary network Figure 25. 9 A–D B The kidney 3 Distal tubule From another nephron Bowman’s capsule Nephron tubule Renal artery Renal vein Collecting duct D Detailed structure of a nephron Renal cortex Renal medulla To renal pelvis C Orientation of a nephron within the kidney

Kidney dialysis can be a lifesaver – Compensating for kidney failure • A dialysis machine removes wastes from the blood and maintains its solute concentration Line from artery to apparatus Pump Line from apparatus to vein Figure 25. 12 Tubing made of a selectively permeable membrane Dialyzing solution Fresh dialyzing solution Used dialyzing solution (with urea and excess ions)

各種不同的螢光魚 A Udvadia and Linney, 2003 Ju et al. , 2003 Huang et al. , 2003 Park et al. , 2000 C Her et al. , 2003 Hagashijima et al. , 2000 This study

DLAV 1 2 3 4 5 6 7 8 9 10 YE MOCK UO 36 hpf 19

小鼠與斑馬魚腎臟發育過程之比較 Drummond, 2003, Trends Cell Biol

Tested compounds Normal kidney Malformed kidney Sodium benzoate NSAID Aristolochic acid Glomerular filtration rate (GFR) assays

苯甲酸鈉(sodium benzoate) Duration: 24 -48 h Tsay et al. , 2007

Nonsteroidal Antiinflammatory Drug (NSAID) Ibuprofen Diclofenac Acetaminophen

NSAID會造成腎損傷 No treatment Diclofenac Ibuprofen Acetaminophen Duration: 12 -24 h Peng et al. , 2010

馬兜鈴酸之化學結構式 (Chem. IDPlus 2004 b, IARC 2002)

中草藥腎病(CHN)或 馬兜鈴酸腎病(AAN)？ • 1993 Vanherweghem, Lancet • 1990“粉防己(Stephania tetrandra)”和“廣防己(Aristolochia fangchi)” • 腎小管上皮細胞壞死及腎間質纖維化(rapidly progressive interstitial renal fibrosis) • 急性腎衰竭(Acute renal failure) 和泌尿上皮細胞癌症(Urothelial carcinoma)

浸泡馬兜鈴酸後原腎之不同畸形型態 A gl pt B pd Mock C 48 hpf D Ding and Chen, 2012, Toxicol Appl Pharmacol

馬兜鈴酸造成斑馬魚之腎功能低下 Control No treatment Method VIII After 1 hr After 24 hr Ding and Chen, 2012, Toxicol Appl Pharmacol

馬兜鈴酸導致斑馬魚腎臟功能受下降 　 　 Group 　 　 　 Glomerular filtration rates (means ±SD%) No treatment 100± 6. 36 88. 38± 6. 36 Method VII 71. 48± 14. 67 63. 17± 14. 67 Method VIII 39. 41± 15. 88 　 34. 83± 15. 88 　 　

馬兜鈴酸造成斑馬魚之紅血球堆積 36 hpf MOCK 48 hpf AA MOCK AA A E I M B F J N C G K O D H L P 34 Ding and Chen, 2012

Normal kidney Toxin exposure Kidney failure Drug and toxin Kidney return to normal Drug treatment

Blocking the Development of Cancer

白藜蘆醇與熊果酸會減低馬兜鈴酸引起之腎臟型態 改變 0 12 24 31 Resv or UA A Developmental stages (hpf) AA B MOCK C 5 ppm AAI+10 ppm RESV 5 ppm AA D 5 ppm AAI+10 ppm. UA 48 hpf

白梨蘆醇與熊果酸可中和掉馬兜鈴酸之腎毒性 　 　 Group 　 　 　 Glomerular filtration rate (means %) 　 　 No treatment 100 77. 18 5 ppm AA 60. 09 46. 38 10 ppm Resv預防 82. 28 63. 5 10 ppm UA預防 85. 23 65. 78 　 　 　 　 After 1 hr After 24 hr No treatment 5 ppm AA 10 ppm Resv 預防 10 ppm UA 預防

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