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王广基, Miao Chen, Guang-Ji Wang, Yong Diao, Rui-An Xu, Hai-Tang Xie, Xin-Yan Li, Jian-Guo Sun, Miao Chen, Jiangsu
R World J Gastroenterol July 14, 2005 Volume 11 Number 26,-0001,():
-1年11月30日
AIM: To investigate the effects of adeno-associated virus (AAV) mediated expression of human interferon-γ for gene therapy in experimental hepatic fibrosis in vitro and in vivo. METHODS: We constructed the recombinant AAV encoding human INF-γ (rAAV-INF-γ) and took the primary rat hepatic stellate cells and carbon tetrachloride induced rats as the experimental hepatic fibrosis model in vitro and in vivo. Immunocytochemistry analysis was used to reveal the expression of α-SMA, the marker protein expressed in hepatic stellate cells. The mRNA expression of TGF-β, TIMP-1, and MMP-13 were analyzed by RT-PCR method. In vivo study, the hydroxyproline content in liver and serum AST, ALT were also detected. RESULTS: In vitro study, AAV vector could mediated efficient expression of human INF-γ, which inhibit the activation of hepatic stellate cells, decrease the expression of α-SMA and mRNA of TIMP-1, TGF-β, with the MMP-13 unchanged. In vivo study, the histological examination revealed that rAAV-INF-γ could inhibit the progression of the hepatic fibrosis. In the rAAV-INF-γ induced group, the hydroxyproline content and serum AST, ALT level were decreased to 177±28μg/g wet liver, 668.5±140.0, 458.4±123.5U/L, compare with the fibrosis control group 236±31μg/g wet liver, 1019.1±276.3, 770.5±154.3U/L, respectively (P<0.01). mRNA expression of TIMP-1 in the rAAV-INF-γ induced rat liver was decreased while no significant change was observed in TGF-β and MMP-13.CONCLUSION: All these results indicated that rAAV-INF-γ has potential effects for gene therapy of hepatic fibrosis, which could inhibit the progression of hepatic fibrosis.
Adeno-associated virus, Interferon-γ, Hepatic stellate cells, Hepatic fibrosis
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【期刊论文】Pharmacokinetics of Guanfu Base I, an Active Metabolite of Guanfu Base A, in Rats
王广基, Xiaotian LI, Guangji WANG, * Sujun WANG, Jianguo SUN, and Jinghan LIU
Biol. Pharm. Bull. 28 (8) 1363-1365 (2005),-0001,():
-1年11月30日
A liquid chromatographic-mass spectrometric (LC-MS) method was developed and validated for determination of guanfu base I (GFI), and the pharmacokinetics of GFI in Sprague-Dawley rats was examined. The method was linear in the 0.05-20mg/ml concentration range (r=0.9994). The recovery of guanfu base I was more than 80%. The intraday and interday precision, expressed as the relative standard deviation (RSD), was generally good (<15%). After i.v. dosing, plasma GFI concentration declined in a bi-phasic manner with a terminal elimination half-life of 2.49h. The total plasma clearance values was 1.46l/h/kg. After oral dosing, the plasma GFI concentration reached a maximum within 0.5h. The absolute bioavailability of GFI was 71.31%.
guanfu base I, pharmacokinetics, LC-MS
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王广基, Qi ZHANG, Guang-ji WANG, Jian-guo SUN
Acta Pharmacol Sin 2004 Aug; 25 (8): 991-995,-0001,():
-1年11月30日
AIM: To study the pharmacokinetics of recombinant human basic fibroblast growth factor (rhbFGF) in rabbits and mice after iv and postocular administration, and the changes of rhbFGF in rabbits aqueous humor after postocular administration. METHODS: After iv or postocular administration three doses of rhbFGF in rabbits and mice, rhbFGF concentration in serum and rabbit aqueous humor was determined by enzyme-linked immunosorbent assay. RESULTS: Serum concentration-time data of rabbits after iv administration of rhbFGF 1, 2, and 4μg/kg were fitted to bi-exponential equations with half-lives of 0.9, 0.9, and 0.6min for T1/2α and 7, 8, and 4.7min for T1/2β. Plasma concentration-time data of mice after iv administration of rhbFGF 2.5, 5 and 10 μg/kg were fitted to biexponential equations with half-lives of 0.4, 0.6, and 0.9min for T1/2α and 6, 5, and 7min for T1/2β. The AUCs were linearly correlated to doses in both cases (rrabbit=0.997, rmouse=0.999). The serum concentrations of rhbFGF were very low, near to the background after postocular administration of 2 or 5μg/kg, in both rabbits and mice. The rhbFGF levels in rabbits aqueous humor were higher than control 8h postdose (P<0.01). CONCLUSION: rhbFGF within the examined doses had a linear pharmacokinetics in rabbits and mice. High concentration of rhbFGF was found in rabbits aqueous humor after postocular administration.
fibroblast growth factor 2, pharmacokinetics, enzyme-linked immunosorbent assay, aqueous humor, rabbits, mice
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王广基, Yongchuan Gu a, b, *, Guangji Wang a, J. Paul Fawcett b
Journal of Chromatography B, 801(2004)285-288,-0001,():
-1年11月30日
Astragaloside Ⅳ (AGS-Ⅳ) is an active constituent of Radix Astragali used in many Traditional Chinese Medicines. This paper describes a sensitive and specific assay for the quantitation of AGS-Ⅳ in rat plasma. After solid phase extraction (SPE), samples were analyzed by liquid chromatography electrospray ionization mass spectrometry using a reversed-phase C18 column. The assay was linear in the range 1-500ng/ml with a limit of detection of 0.5ng/ml. The recovery was 92.5% and within-day and between-day precision were 3.7-6.0 and 2.8-9.8%, respectively. The assay was applied to a pharmacokinetic study in rat after a single oral dose. The drug was rapidly absorbed and subsequently eliminated according to a biphasic concentration-time curve.
Astragaloside Ⅳ
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王广基, YANG Hai-Tao, WANG Guang-Ji
Acta Pharmacol Sin 2003 Dec; 24 (12): 1185-1191,-0001,():
-1年11月30日
AIM: The characteristics of transepithelial transport and uptake of CPU-86017 {[7-(4-chlorbenzyl)-7,8,13,13-tetrahydroberberine chloride, CTHB]}, a new antiarrhythmia agent and a new derivative of berberine, were investigated on epithelial cell line (Caco-2) to further understand the absorption mechanism of berberine and its derivatives. METHODS: Caco-2 cell was used. RESULTS: 1) The permeability coefficient from the apical (AP) to basolateral (BL) of CPU-86017 was approximately 5 times higher than that from BL-to-AP transport. The effects of a P-glycoprotein (P-gp) inhibitorcyclosporin A, some surfactants, and lower pH on the transepithelial transport of CPU-86017 were also observed. Cyclosporine A at 7.5mg/L had no effect on the transepithelial electrical resistance (TEER); an about 4-fold enhancement on the transepithlial transport of CPU-86017 was observed. Some surfactants (sodium citrate, sodium deoxycholate, and sodium dodecyl sulfate) at 100μmol/L and low pH (pH=6.0) induced a reversible decrease of TEER; enhancements of the transepithelial transport of CPU-86017 were also observed with some surfactants; 2) In the process of uptake of CPU-86017, the initial uptake rates of CPU-86017 were saturable with a Vmax of (250±39) μg•min-1•g-1 (protein) and Km of (0.90±0.12)mmol/L. This process was enhanced by cyclosporine A (7.5mg/L) with a Vmax of (588±49)μg•min-1•g-1 (protein) and Km (0.42±0.08)mmol/L. CONCLUSION: Some surfactants and P-gp inhibitors can be considered as enhancers of its transepithelial transport and uptake.
CPU-86017, berberine, Caco-2 cell, cyclosorine A, sodium dodecylsulfate, doldium citrate, sodium deoxycholate
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