AIM To establish hyperuricemia animal model. METHODS The mice were given uric acid by ip and then the level of uric acid in serum was detected. RESULTS Uric acid 125,250,500, 1 000 mg?kg -1 ip significantly increased the level of uric acid in mouse serum. The level of uric acid in mouse serum was attained peak at 10 min and the hyperuricemia could lasted over 4 hours after uric acid 250 mg?kg -1 given. CONCLUSION Uric acid given by ip can form mouse hyperuricemia model, the dosage of 250 mg?kg -1 is better.

Homocysteine ( Hcy) is an independent risk factor for a variety of diseases and closely related to cardiac-cerebralvascu-lar diseases, neurological diseases, diabetes and diabetic com-plications. High homocysteine levels can significantly increase the recurrence risks of cardiac-cerebralvascular events and stroke in patients with stroke, leading to high all-cause mortality. The risk of Alzheimer’s disease is increased by 1. 8 fold when the concentration of Hcy is over 14 μmol·L-1 . For each 5 μmol· L-1 increase in plasma Hcy in diabetes patients, the mortality rate increases by 5 fold in the next five years. High Hcy triggers the pathogenesis of diseases via multiple mechanisms including oxidative stress, lesions of vascular endothelial cells, prolifera-tion of vascular smooth muscle cells, dysfunction of coagulation and lipid metabolism and genomic hypomethylation etc.

Uric acid is an end product of purine degradation in humans and normally depends upon renal excretion for the majority. Hyperuricemia is likely to cause gout, renal disease, or stones, and associated with cardiovascular impairment over the long term. The prevalence of gout and hyperuricemia appears to be on the increase in recent years. The present paper reviews the relationships between hyperuricemia and insulin resistance,purine metabolism and uric acid elimination , the genetics study and the mechanisms of hyperuricemia.

Hyperuricemia is induced by the mechanism of the elevated production of uric acid or the decreased renal excretion of uric acid. At present, there are three major methods to establish models for hyperuricemia: first, it will elicit pronounced hyperuricemia when feeding or injecting the animal with hypoxanthine 600～1000 mg?kg -1 , xanthine 600 mg?kg -1 , adenine 150～300 mg?kg -1 , yeast 15～30 g?kg -1 , uric acid 250 mg?kg -1 or 350～700 mg?kg -1 because of the elevated serum uric acid. Such effect will be also observed as administrating the animal with the inhibitors of uric acid excretion such as ethambutol 250 mg?kg -1 , nicotinic acid 100 mg?kg -1 at the same time of the above steps. Second, being an uricase inhibitor, when fed the rats 0 4 g?d -1 and uric acid 0 6 g?d -1 for 3～4 weeks, oxonic acid is able to cause the continuously elevated serum uric acid. Similarly, when potassium oxonate 300 mg?kg -1 ip only once, the serum uric acid in mice will be also elevated. Third, to destruct the urate oxidase gene (EC 1.7.3.3) in the mouse by homologous recombination in embryonic stem cells, and then the oxidase deficient mutant mouse as the hyperuricemia model, is generated by gene recombination.The rats and the mice have urate oxidase, which can decompose the uric acid to allantoin, while the avian (such as chicken, coturnix and so on) have not.

AIM　This paper was to review the methods of establishing experimental animal models of intrauterine growth retardation (IUGR) and their observed index. METHODS　Passive smoking, passive smoking plus drinking wine, NG nitro-L-arginine methyl ester, dactinomycin, thiamine deficiency plus pyrithiamine, or ligating the uterine artery during pregnancy were used.RESULT　The fatal and maternal body weight was lower body length; was shorter; infant physique and nerve system development was slow.CONCLUSION　The above methods could establish animal models of IUGR.

Aim Toinvestigatetheeffectsoftotalsap-onin of Dioscorea (TSD)on rats with monosodium u-rate crystal-induced acute gouty arthritis (AGA)and mechanisms.Methods Totally72Wistarratswere randomly devided into six groups,Each group was giv-en corresponding drug before,then rat acute gouty ar-thritis model was made by injection of monosodium u-rate in the ankle joint cavity.The gait,articular swell-ing degree and physiological changes of rats were ob-served.The concentration of TNF-α,IL-1β,IL-18 in serum were detected by ELISA.The levels of pro-IL-1β, NALP3, ASC, pro-caspase-1, and cleaved caspase-1 were detected by Western blot.Results AllTSDgroupsandcolchicinesignificantlychangedthe gait of rats and TSD high and middle groups signifi-cantly reduced joint swelling and diminished the patho-logical changes.The levels of TNF-α,IL-1β,IL-18 in serum were significantly decreased,and the levels of pro-IL-1β,NALP3,ASC,pro-caspase-1 and cleaved caspase-1 were apparently reduced in TSD high and middlegroups.Conclusion TSDpossessesanti-goutfunction and the mechanism may be related to sup-pressing the NALP3 inflammasome activation and in-hibiting the cytokine production.

Transforming growth factor-β1(TGF-β1)has become an important biological marker and therapeutic target of clinical progression of chronic kidney diseases. Sma- and Mad-related protein (Smad)is a downstream signal transduction protein of the TGF-β family. TGF-β1 activates Smad2 and Smad3 before increasing the transcription of connective tissue growth factors in the nucleus. Smad3 promotes mesangial cell proliferation,extracellular matrix accumulation,epithelial-mesenchymal transition, leading to renal fibrosis. However,Smad2 and Smad7 play a negative regulatory role by inhibiting renal fibrosis. TGF-β1 specific inhibitor (SB431542,etc.) has antifibrosis effect,most of which is in the preclinical stage. The drugs on the market that are effective for DN,such as benzodiazepines,atorvastatin, losartan,and pirfenidone,can inhibit the expression of TGF-β1,while tripterygium wilfordii,cordyceps sinensis,and berberine can delay the process of diabetic nephropathy by reducing TGF-β1 levels.

OBJECTIVE:To study the in vitro dissolution of Enalapril maleate and folic acid tablet. METHODS:HPLC was performed on the column of Agilent HC-C18 with mobile phase A of acetonitrle-phosphate buffer solution(70:30,V/V) and mobile phase B of acetonitrle-phosphate buffer solution(5:95,V/V)(gradient elution) at a flow rate of 1.0 ml/min,detection wavelength was 215 nm,column temperature was 50 ℃,and volume injection was 80 μl. Media were water,hydrochloric acid solution(pH 1.2),phosphate buffer solution(pH 5.0)and phosphate buffer solution(pH 6.8),medium volume was 900 ml and rotation speed was 50 r/min. The dissolution behavior of enalapril maleate in Enalapril maleate and folic acid tablet in 4 media were studied and compared with the dissolution behavior in vitro in original preparation of Enalapril maleate tablet,meanwhile,the dissolution behar-ior of folic acid in Enalapril maleate and folic acid tablet in phosphate buffer solution(pH 5.0)were studied and compared with dis-solution data of folic acid preparation in Japanese Orange Book to evaluate the intrinsic quality. RESULTS:The linear range was 0.561-14.03μg/ml for enalapril maleate(r=0.999 9)and 0.043-1.085μg/ml for folic acid(r=0.999 9),respectively;RSDs of pre-cision and stability tests were lower than 2.0%;recoveries of enalapril maleate in 4 media were 100.63%-102.33%(RSD=0.72%, n=9),99.27%-100.44%(RSD=0.41%,n=9),99.71%-100.29%(RSD=0.15%,n=9)and 96.74%-99.19%(RSD=0.79%,n=9),respectively. Recoveries of folic acid were 100.18%-101.63%(RSD=0.48%,n=9),97.73%-101.81%(RSD=1.32%,n=9),99.60%-102.24%(RSD=0.74%,n=9)and 100.00%-102.76%(RSD=0.90%,n=9),respectively. In 15 min,the dissolution of enalapril maleate of 2 preparations in 4 dissolution media were more than 85%;dissolution speed of folic acid in Enalapril male-ate and folic acid tablet was faster than that in folic acid preparation in phosphate buffer solution(pH 5.0). CONCLUSIONS:The method is suitable to determine the dissolution of Enalapril maleate and folic acid tablet;the in vitro dissolution curve of enalapril maleate in Enalapril maleate and folic acid tablet is similar to Renitec,and the in vitro dissolution of folic acid is better than folic acid preparation.

We first report the pharmacokinetics of paeoniflorin ( PF), that is a main component of paeony roots, in dogs by HPLC analysis. The experimental results were shown that after i .v . of 11.25 mg/kg PF in 4 dogs, the curve of plasma concentrations versus times for PF was fitted well to a open 2 compartment model, the T1/2 (?) was 6.29?1.80min T1/2 ( ? ) was 133.41?84.89 min, VB was 0.54 ? 0.10 L/kg, andCL was 3.41 ? 1.01ml/min?kg-1 .The results also were shown that PF was rapidly removed from the blood by kidney and the accumulated recovery amounts of excretion was 36.85% and 79.33% of total i .v . doses during 20 min and 7h administrations respectively. The elimination of PF by liver was lower than by kidney, and the accumulated amount of PF in bile was only 3.77% within 7h after iv.

Object To observe the effect of gypenosides (GP) on the DNA and RNA in cerebral cortex and hippocampus in vascular dementia rat. Methods Modified Pulsinelli 4 vessel occlusion (4 VO) method was used to establish the models of vascular dementia rat. The acridine orange (AO) method was applied to study the protective effect of GP on the DNA and RNA of cerebral cortex and hippocampus in vascular dementia rat. Results The fluorescent intensity from the DNA and RNA in cerebral cortex and hippocampus of vascular dementia rat is abated as compared with the normal control group. The fluorescent intensity from DNA and RNA of the treatment group administrated GP (200 mg/kg, ig) significantly intensified, as compared with that of non treatment group, and is similar to that of normal group. Conclusion The injury to the DNA and RNA in cerebral cortex and hippocampus in vascular dementia rat was obviously decreased by GP.