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OBJECTIVE To investigate the effect of Radix Isatidis and its constituents indigo and in?dirubin on two principal subtypes of organic cation transporters(OCT)OCT1,OCT2 in vivo in mice. METHODS Decoction of Radix Isatidis (DRI) 1.6 and 6.4 g · kg-1,granules of Radix Isatidis (GRI) 0.615 and 2.460 g·kg-1,indigo 0.008 and 0.640 mg·kg-1 and indirubin 0.0192 and 1.536 mg·kg-1 were ig given to NIH mice(60 mice per group),twice a day for 5 d. Four control groups were set up,including the vehicle of water,0.5% sodium carboxymethyl cellulose(CMC),additives of sucrose plus dextrin (1.5 g · kg-1)and positive control quinidine(0.025 g · kg-1). Sixty minutes after the last dosing,all the mice were iv given metformin(Met)5 mg·kg-1,and at 1.0,2.5,5.0,7.5,10.0 and 20.0 min after Met iv,10 mice in each group were sacrificed to collect whole blood and kidneys respectively. The right kidney was homogenized for Met accumulation test and the left one used to extract total RNA for analysis of OCT1 and OCT2 mRNA expressions by real-time PCR. The contents of Met in sera and kidneys were quantified by HPLC. Major pharmacokinetic parameters of Met in sera were analyzed by pharmacokinetic software(DAS 2.0). RESULTS There was no significant difference between water control group,0.5%CMC group and sucrose plus dextrin group in any examined item. Compared with vehicle control group (water and 0.5%CMC group),all the related pharmacokinetic parameters in DRI 6.4 g · kg- 1,GRI 2.46 g · kg-1,indigo 0.640 mg · kg-1 and indirubin 1.536 mg · kg-1 groups were changed significantly (P<0.05,P<0.01). The elimination half time (t1/2β) was prolonged 13%-97%,volume of distribution reduced by 13%-72%,clearance(Cl)reduced by 9%-65%,and the area under the concentration-time curve (AUC0-20 min) increased by 13%-135%. AUC0-20 min obtained from renal Met accumulations was significantly increased(P<0.01)while Met uptake by kidney slices was reduced(P<0.05,P<0.01). The expressions of OCT1 and OCT2 mRNA were obviously down-regulated(P<0.05,P<0.01). CONCLUSION The mouse renal OCT1 and OCT2 are significantly inhibited by DRI,GRI,indigo and indirubin. The inhibitory effect of Radix Isatidis on OCT1 and OCT2 probably arises from indigo and indirubin contained.
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OBJECTIVE:To study the effects of 10 kinds of nephrotoxic TCM on three main subtypes(Oat1,Oat2 and Oat3) of kidney organic anion transporter(Oats)in mice. METHODS:A total of 1 840 SPF NIH mice were randomly divided into nor-mal control group(isovolumic pure water),probenecid group(30 kg/mg),sodium carboxymethyl cellulose(CMC)group,Pulsa-tillae radix,Corydalis rhizoma,Aconiti kusnezoffii radix,Aconiti radix,Angelicae pubescentis radix,Gleditsiae spina,Polygo-num cuspidatum,Kansui radix,Platycladi cacumen,Aucklandiae radix high and low dose groups. Mice were treated twice a day for 5 d,ig. After 1 h of the last dosing,they were iv given PAH in tail(30 mg/kg). The PAH pharmacokinetic parameters of the kidney homogenate were determined and the PAH intake in kidney tissue at the time point of 1,5,10,15 and 20 min was detect-ed. The PAH in blood was analyzed by DAS 2.0 software. The grouping and dosing were the same as before,after 1 h of the last dosing,kidney slices were made and put into PAH-buffer. The PAH intake of kidney slices was determined. RESULTS:Compared with normal control group,the t1/2β in C. rhizoma high dose group,A. kusnezoffii high and low dose groups,A. pubescentis high dose group,P. cuspidatum high and low dose groups and P. cacumen group were increased;Vd were all decreased in 10 kinds of TCM high and low dose groups;except for A. pubescentis low dose group,G. spian low dose group and K. radix low dose group, the CL was decreased and AUC0-20 min was increased in all other groups,with significant difference (P<0.01 or P<0.05). Com-pared with normal control group,the content of PAH in kidney tissue in P. radix high dose group,C. rhizoma high dose group,A. kusnezoffii high dose group,A. radix high and low dose groups,A. pubescentis high and low dose groups,G. spina high and low dose groups,P. cuspidatum high and low dose groups,K. radix high and low dose groups,P. cacumen high and low dose groups and A. radix high and low dose groups were increased,with significant difference (P<0.01 or P<0.05). Compared with normal control group,the intake of PAH in kidney slices in C. rhizoma high dose group,A. kusnezoffii high and low dose groups,G. spi-na high and low dose groups,K. radix high dose group,P. ca-cumen high and low dose groups and A. radix high dose group were decreased,with significant difference (P<0.01 or P<0.05). CONCLUSIONS:The 10 kinds of nephrotoxic TCM probably induced kidney injury through inhibiting the Oat1,Oat2 and Oat3 of Oats.
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Objective To study the role of chromoendoscopy with toluidine blue to diagnose gastric cancer and precancerous change.Methods572 cases were randomized into two groups.288 cases in testing group took gastroscopy with 0.1% toluidine blue sprinkles,while ordinary gastroscopy was applied in 284 cases of control group.We took biopsy in all of those cases for pathology examination.The biopsy was taken from heterochrome area if heterochrome area appeared in testing group,otherwise from suspected affection.ResultsDetection rate of gastric cancer of test groups(9.72%)was higher than that of control groups(5.28%).Both of the methods were significantly different(P