龍膽瀉肝湯變方對Dimethylnitrosamine誘發大鼠肝損傷的療效探討

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1 205 J Chin Med 14(4): , 2003 Dimethylnitrosmine ( ) Dimethylnitrosmine DMN 333 mg/kg 111 mg/kg 1 GOT GPT DMN GOT ± 16.3 U/l ± 9.6 U/l DMN ± 28.2 U/l p < 0.01 GPT ± 5.9 U/l 93.8 ± 7.8 U/l DMN ± 6.4 U/l p < ± 0.2 & 4.4 ± 0.1 g/dl DMN 5.8 ± 0.4 & 4.1 ± 0.2 g/dl p < 0.05 DMN p < 0.05 DMN p < 0.05 p > 0.05 DMN p > Fx: E-mil: ytchiu@vghtc.gov.tw

2 DMN 4 ( ) ( ) C ( ) 1. LDXGTH mg/kg 2. LDXGTL mg/kg

3 207 5 SD 12 light/drk 8 DMN DMN Silymrin DMN 3 IP 0.1 ml 1 % DMN / 100 gbw DMN 4 10 w/v 8 mm KH 2 PO 4, 12 mm K 2 HPO 4, 1.5 % KCl, ph C 4 C 4700 rpm 20 GOT GPT totl protein RANDOX Lbortories Antrum, UK kit H&E Sirius red H&E multifocl + loclly extensive + diffuse Sirius red

4 208 1 H&E A B + C + D + 2 H&E A B + C + D

5 209 3 Sirius red A B + C + D + Hydroxyproline HYP HYP 3 ( ) % SSA 5-sulfoslicylic cid rpm, N NHCO 3 ph = N 3 BO 3 ph = 7.6 ( )Hydroxyproline 1. 1 µm, 5 µm, 10 µm, 20 µm, 50 µm Hydroxyproline 15 mm FMOC 9-fluorenylmethyl chloroformte HPLC 2. Hewelett Pckrd 1100 series BAS FL-45 excittion λ = 270 nm emission λ = 316 nm HP chem. Sttion Alltech, 150 mm 4.6 mm Econosphere C-18 5 µm

6 Mobile Phse GAST Vccum Pump 0.45 µm MILLIPORE 1 M mmonium phosphte, 15 % Methnol 15 % Methnol 90 % cetonitrile 4. Elution Grdient min A B C SigmStt nlysis of vrince ANOVA t-test Mnn-Whitney Rnk Sum test p < GOT ± 16.3 U/l ± 9.6 U/l) Silymrin ± 16.7 U/l) DMN ± 28.2 U/l p < 0.05 GPT ± ± 7.8 U/l Silymrin ± 7.1 U/l DMN ± 6.4 U/l p < 0.05 GOT GPT Silymrin p < 0.05 DMN GOT GPT Silymrin 6.2 ± 0.2 & 4.4 ± 0.1 g/dl DMN 5.8 ± 0.4 & 4.1 ± 0.2 g/dl p < 0.05 p > 0.05

7 211 1 Silymrin DMN DMN Silymrin 111 mg/kg 333 mg/kg GOT U/l ± ± 28.2 b ± 16.7 c ± 16.3 d ± 9.6 e GPT U/l 45.4 ± ± 6.4 b ± 7.1 c ± 5.9 d 93.8 ± 7.8 de Totl protein g/dl 5.9 ± 0.3 b 5.8 ± ± 0.2 b 6.1 ± 0.1 b 6.2 ± 0.2 b Albumin g/dl 4.0 ± ± ± ± ± 0.1 b p < Silymrin DMN DMN Silymrin 111 mg/kg 333 mg/kg g 25.2 ± ± 2.0 b 22.2 ± 2.4 b 21.8 ± 2.1 b 23.5 ± 1.9 g 0.9 ± ± 0.2 b 1.2 ± 0.2 b 1.4 ± 0.1 b 1.3 ± 0.2 b g 4.2 ± 0.4 b 3.7 ± ± 0.2 b 3.8 ± 0.3 b 4.2 ± 0.5 b p < Silymrin DMN P P P DMN Silymrin mg/kg mg/kg b bc c b b b P p < Silymrin DMN hydroxyproline DMN Silymrin 111 mg/kg 333 mg/kg Hyp µmoles/g ± ± ± ± DMN 2

8 ± 1.9 g & 4.2 ± 0.5 g DMN 21.4 ± 2.0 g & 3.4 ± 0.4 g p < 0.05 p > 0.05 H&E Sirius red & Fst green DMN p < 0.05 Silymrin p < 0.05 DMN p > 0.05 DMN 4 p > 0.05 B % 4 ~ 2 5

9 213 6 GOT GPT GGT 7 Biclin Biclein Antioxidtive ctivity Retinoid Collgen Mlodildhyde MDA Heptic fibrosis DMN GOT GPT DMN p < 0.05 p < 0.05 DMN p < 0.05 DMN p < 0.05 DMN p > 0.05 DMN p > 0.05 GPT GOT 10

10 214 TCVGH A VTY92-P pp Hynes PA, Sheumck D, Kibby J, Redmond JW. Amino cid nlysis using derivtistion with 9- fluorenylmethel chloroformte nd reversed-phse high-performnce liquid chromtogrphy. J Chromtogrphy 540: , pp pp Shimizu I, MA YR, Mizobuchi Y, Liu F, Miur T, Nki Y, Ysud M, Shib M, Horie T, Amgy S, Kwd N, Hori H, Ito S Effect of Sho-siko-to, Jpnese herb medicine on heptic fibrosis in rts. J Heptology, 29: , pp

11 215 J Chin Med 14(4): , 2003 STUDIES ON THE THERAPEUTIC EFFECTS OF DEVIATED LONG-DAN-XIA-GAN-TANG ON DIMETHYLNITROSAMINE INDUCED HEPATIC DAMAGE IN RATS Long-Yun Wu 1, Hsio-Ping Hsu 3, Yi-Shin Chen 2, Ni-Nu Lin 2, Wn-Chun Chen 4, Zheng-Hung Cheng 5, Wen-Hung Peng 5 nd Yung-Tsung Chiu 2 1 Post-Bcclurete School of Chinese Medicine, Chin Medicl College 2 Deprtment of Eduction nd Reserch, Tichung Veterns Generl Hospitl 3 Deprtment of Veterinry Medicine, Ntionl Chung Hsing University Tichung, Tiwn 4 Doctor Trde Union of trditionl Chinese medicine in Tipei 5 Tipei City-mintined Hospitl of Chinese Medicine Tipei, Tiwn (Received 6 th My 2003, revised Ms received 14 th July 2003, ccepted 9 th September 2003) To ssy the heptic protection nd the nti-cirrhotic effect of Long-Dn-Xi-Gn-Tng, we used dimethylnitrosmine (DMN) to induce liver dmge in rts. These rts were first fed with 1 % DMN three times per week for 4 weeks, nd were then fed with low nd high doses (111 mg/kg, 333 mg/kg) of this herbl drug once time per dy for 4 weeks. Assy indictors for the therpeutic effect include: 1) serum biochemicl tests, such s GOT, GPT, totl protein nd lbumin, 2) gross lesion findings, 3) histopthologicl score of degenertion, necrosis of heptocyte, nd heptic fibrosis, nd 4) collgen determintion in liver tissues. The results show tht this herbl drug significntly decresed the contents of GOT (p < 0.05), GPT (p < 0.05), totl protein nd lbumin (p < 0.05), nd the degrees of DMN-induced heptic degenertion nd necrosis (p < 0.05). However, the occurrence of heptic fibrosis in histopthologicl score nd the collgen determintion were not significntly different from those in the control rts (p > 0.05). These findings indicte tht Lon-Dn-Xn-Tng exerted significnt effects on the heptic protection, but not on the inhibition of heptic fibrosis. Conclusively, this herbl drug my hve therpeuticl role in the cute stge of liver disese. Key word: Cirrhosis, Anti-fibrosis, Long-Dn-Xi-Gn-Tng, Rt model. Correspondence to: Yung-Tsung Chiu, Tel: ext. 4060, Fx: , E-mil: ytchiu@vghtc.gov.tw

中草药 Chinese Traditional and Herbal Drugs 第 46 卷第 9 期 2015 年 5 月 1339 非酒精性脂肪性肝病 (nonalcoholic fatty liver disease,nafld) 是一种与胰岛素抵抗遗

中草药 Chinese Traditional and Herbal Drugs 第 46 卷第 9 期 2015 年 5 月 1339 非酒精性脂肪性肝病 (nonalcoholic fatty liver disease,nafld) 是一种与胰岛素抵抗遗 1338 中草药 Chinese Traditional and Herbal Drugs 第 46 卷第 9 期 2015 年 5 月九味肝泰胶囊对高脂饮食诱导大鼠非酒精性脂肪肝的治疗作用陈菲 1 2,, 艾国 3, 盛柳青 1, 麻佳蕾 1, 黄正明 1. 金华职业技术学院医学院, 浙江金华