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Establishment Of A Rat Model Of Gouty Arthritis And Study On Chinese Medicine For Treatment Of Gouty

Posted on:2008-10-15Degree:MasterType:Thesis
Country:ChinaCandidate:Q Y XuFull Text:PDF
GTID:2144360218458921Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Objective: The present investigation was undertaken to establish a rat model of gouty arthritis and compare three methods of measuring the degree of ankle joint swell, and study the dose-effect relationship and the mechanism of inhibiting the inflammatory response of gouty arthritis and reducing hyperuricemia of the optimum compound chinese medicine JFX-H-50-30 selected form three compound chinese medicines in pre-experiment. Our data thus may offer a foundation for the further development of new drug.Methods: (1) We compared two models of acute gouty arthritis were prepared by injecting into the articulatio tibiotarsalis cavity of rat ankle with two different concentrations of sodium urate. (2) We selected the optimum measurement through comparing the merits and demerits of the measurements for circumference and diameter and weight of swollen joints in three groups: Indomethacin, compound chinese medicine and vehicle control, which the model of acute gouty arthritis was prepared by 5% sodium urate. (3) The pharmacodynamic studies of three compound chinese medicine ware undertaken to determinate the optimum one, PVP and indomethacin was considered as vehicle control and the positive control, respectively. (4) The pharmacodynamic studies and dose-effect responses of six concentrations of the compound Chinese medicine JFX-H-50-30 were studied, PVP and indomethacin was respective considered as vehicle control and the positive control. (5) The rabbit was divided into three groups: vehicle control (PVP), positive control (indomethacin), JFX-H-50-30 (compound chinese medicine). The model of acute gouty arthritis was prepared by injecting into the cavity of rabbit knee joint with 5% concentration of sodium urate. White blood cell count of knee joint fluid was determined by microscope. (6) Mice were randomized into six groups: normal, hyperuricemia (PVP vehicle control), compound Chinese medicine (low concentration, middle concentration, high concentration) and Allopurinol. Oteracil potassium (900 mg/kg) was injected by I.P. except for the control group with normal saline. Mice were bled from the orbital venous plexus and serum was evaluated for urate acid by automatic biochemical analyzer.Results: (1) The degree of ankle joint swell after injecting 50μl 1.3% uric acid sodium salt solution was instability and the swell dissipated naturally. But the degree of ankle joint swell after injecting 50μl 5% uric acid sodium salt solution was sustained with high level after the model established. (2) Among the measurements for circumference and diameter and weight of swollen joints in three groups, the circumference measurement was considered as the optimum one through comparing different indicators, which concludes convenience, error, sensitivity, time course, et al. (3) In the preliminary screening for three compound Chinese medicines, we found that JFX-H-50-30 and JFX-H-50-60 both have significant anti-inflammatory effect compared with blank control group, and the anti-inflammatory effect of JFX-H-50-30 was better than JFX-H-50-60, and JFX-H-100-60 has not this effect. (4) The 1.0g/kg, 0.75 g/kg, 0.50 g/kg groups of JFX-H-50-30 all have remarkable significant anti-inflammatory effect (P < 0.01), 0.30 g/kg and 0.10 g/kg groups of JFX-H-50-30 have significant anti-inflammatory effect (P < 0.05), and 0.10 g/kg group of JFX-H-50-30 has no this effect. The effect dose range of JFX-H-50-30 is 0.10 g/kg to 1.0 g/kg . (5) Compared with PVP vehicle group (model group), white blood cell count of knee joint fluid of JFX-H-50-30 group has significant decreased (P<0.05), which shows that JFX-H-50-30 has anti-inflammatory effect. (6) Three doses of compound Chinese medicine all could decrease serum uric acid level in model of hyperuricemia mice (P<0.01,P<0.01,P<0.01), compared with model group. Conclusions: (1) The different concentration of uric acid sodium salt solution could affect the degree of joint swell. Our study indicates that 5% uric acid sodium salt solution was appropriate for rat model of gouty arthritis, and 50μl was the optimum volume of injection. (2) Choosing different ankle and different time didn't affect the measurement of swollen joints. Taking convenience, error, sensitivity and time course into account, the method of measuring perimeter was the best. (3) JFX-H-50-30 and JFX-H-50-60 both have significant anti-inflammatory effect, and the anti-inflammatory effect of JFX-H-50-30 was better than JFX-H-50-60, and JFX-H-100-60 has not this effect. (4) The effect dose range of JFX-H-50-30 is 0.10 g/kg to 1.0 g/kg . (5) JFX-H-50-30 could significant decrease white blood cell count of knee joint fluid of acute gouty arthritis rabbit. (6) Compound Chinese medicine could decrease serum uric acid level in model of hyperuricemia mice. (7)JFX-H-50-30 has effect about anti-inflammatory and could decrease serum uric .It has a good exploitation value.
Keywords/Search Tags:Arthritis, gouty, models, compound Chinese medicine, antiinflammatory, hyperuricemia
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