鸡矢藤提取物对酵母膏和氧嗪酸钾致小鼠高尿酸血症的影响

目的探讨鸡矢藤提取物(EPS)对酵母膏和氧嗪酸钾致小鼠高尿酸血症的影响及可能的作用机制。方法采用酵母膏和氧嗪酸钾造成小鼠高尿酸血症模型,观察EPS对模型小鼠血清尿酸水平及体重和肾功能的影响,并进一步观察其对模型小鼠黄嘌呤氧化酶和腺苷脱氨酶的抑制作用。结果EPS(6.3、3.15、1.57g/kg,ig,qd×14d)在显著降低高尿酸血症小鼠血清尿酸水平的同时,对模型小鼠体重和肾功能均无明显影响;EPS(6.3、3.15、1.57g/kg,ig,qd×14d)可显著抑制高尿酸血症小鼠肝脏黄嘌呤氧化酶的活性,EPS(6.3g/kg)对模型小鼠血清腺苷脱氨酶的活性也具有一定的抑制作用。结论EPS可显著降低酵母膏和氧嗪酸钾致高尿酸血症小鼠的血清尿酸水平,其机制可能与抑制黄嘌呤氧化酶和腺苷脱氨酶活性有关。

Oxidative stress and hypoxia-induced factor 1α expression in gastric ischemia

AIM:To investigate the relation of reactive oxygen species (ROS) to hypoxia induced factor 1α (HIF-1α) in gastric ischemia. METHODS:The animal model of gastric ischemia reperfusion was established by placing an elastic rubber band on the proximal part of the bilateral lower limb for ligature for 3 h and reperfusion for 0,1,3,6,12 or 24 h. Ischemic post-conditioning,three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were conducted before reperfusion. Histological and immunohistochemical methods were used to assess the gastric oxidative damage and the expression of HIF1-α in gastric ischemia. The malondialdehyde (MDA) content and superoxide dismutase (SOD),xanthine oxidase (XOD) and myeloperoxidase (MPO) activities were determined by colorimetric assays. RESULTS:Ischemic post-conditioning can reduce post-ischemic oxidative stress and the expression of HIF-1α of gastric tissue resulting from limb ischemia reperfusion injury. MDA,SOD,XOD and MPO were regarded as indexes for mucosal injuries from ROS,and ROS was found to affect the expression of HIF-1α under gastric ischemic conditions. CONCLUSION:ROS affects HIF-1α expression under gastric ischemic conditions induced by limb ischemia reperfusion injury. Therefore,ROS can regulate HIF-1α expression in gastric ischemia.

The inhibitory effect of lotus leaf extract on hyperuricemia and its potential mechanism

Objective:Lotus leaf is a traditional Chinese herb that has been used successfully for centuries for relieving edema by inducing diuresis.Based on its good clinical evidence and anti-hypertensive effectiveness,this study aimed to investigate the potential mechanism of the hyperuricemic inhibitory effects of lotus leaf crude extract(LL)and lotus leaf total alkaloids fraction(LA).Methods:The xanthine oxidase(XOD)inhibitory effect of LL and LA was analyzed in vitro by determining mRNA expression and protein expression levels of hepatic XOD.The hyperuricemic inhibitory effect of the lotus leaf was analyzed in vivo in a potassium oxonate(PO)-induced rat model by determining mRNA expression for renal urate transporters.Results:At a concentration of 40mg/mL,LL and LA suppressed XOD enzymatic activity by 37.35%±9.50%and 47.73%±8.32%,respectively.Both LL and LA administration significantly reduced the concentration of uric acid in the serum and liver of PO-induced hyperuricemic rats.Both LL and LA administration could inhibit XOD mRNA and protein expression,activate renal organic anion transporter 1/3 mRNA expression,and inhibit renal urate reabsorption by decreasing renal GLUT9 and renal urate transporter 1.Conclusions:Insight was gained into the mechanism behind the hyperuricemic inhibitory effects of LL and LA.Our results suggest that they act on two targets:decreasing the production of uric acid by inhibiting mRNA and protein expression of XOD in the liver,and regulating the mRNA expression of renal urate transporters in the kidneys.

VASOACTIVE INTESTINAL POLYPEPTIDE PREVENTS INJURY OF PULMONARY VASCULAR PERMEABILITY DUE TO XANTHINE WITH XANTHINE OXIDASE

Hyperpermeability is a crux of pathogenesis of sudden lung edema in many pulmonary disorders. especially in acute lung injury and adult respiratory distress syndrome(ARDS). Using our modified method for assessment of pulmonary vascular permeability. we observed the effects of xanthine with xanthine oxidase(X-XO) perfused in rat pulmonary artery and the protection of vasoactive intestinal polypeptide(VIP) against the injury of pulmonary vascular permeabilrty. After addition of xanthine oxidase in the perfusate reservoir containing xanthine￣(125) I-albumin leak index (￣(125)IALI)was remarkably increased while peak airway pressure(Paw) was not significantly increased, and perfusion pressure of pulmonary artery(Ppa)and lung wet/dry weight ratio(W/D) were only slightly increased. Xanthine plus xanthine oxidase also increased thromboxane B_2(TX B_2) and 6-keto-prostaglandin F_(1α)(6-keto -PGF_(1α)) in the perfusate. Treatment with VIP obviously reduced or totally prevented all signs of injury. Simultaneously, VIP also diminished or abolished the associated generation of arachidonate products. The results indicated that VIP has potent protective activity against injury of pulmonary vascular permeability and may be a physiological modulator of inflammatory damage to vascular endothelium associated with toxic oxygen metacolites.

Preliminary Comparative Study on Antioxidant Capacities of Yak

The aim of the present experiment was to determine if there was an adaptation on plasma antioxidant capacities of yak under the malnutrition （fasting treatment）. Three castrated male yaks and equal numbers of indigenous male cattle and of castrated male cattleyak with mean body weight of 146 ± 5.0, 116 ±3.0 and 149 ± 5.0 kg, respectively, were used. The fasting period lasted for 6 d. Results showed that： plasma total antoxidative capacity （T-AOC） was no differences between the genotypes on the fasting 1 st, 3rd, and 6th （P 〉 0.05）, but the values were linear greater with fasting days for yak, however, it was inverse for indigenous cattle or cattle-yak; plasma xanthine oxidase （XOD） activities of indigenous cattle were less than yak＇s and cattleyak＇s on the fasting 1st and 3rd day （P 〈 0.05）, but the value of indigenous cattle was greater than yak＇s and cattleyak＇s on the fasting 6th day （P 〈 0.05）. In a conclusion, plasma antioxidant capacities indicated that yaks have evolved an ability to survive in a starvation than indigenous cattle, and their crossbred-cattleyak also has inherited some of the adaptive characteristics.

Antihyperuricemic Effect of Ethanol Extract of Snake Fruit （Salacca edulis Reinw.） var. Bongkok on Wistar Male Rat

The aim of the study was to investigate antihyperuricemic effect of snake fruit （Salacca edulis Reinw.） var. Bongkok Wistar male rates. Antihyperuricemic investigation on Wistar male rats showed that administration of ethanol extract at doses of 200 mg/kg bw decreased serum uric acid level significantly compared to control group at hour 6 and 7 （P 〈 0.05） after inducing with potassium oxonate intraperitoneally simultaneously with uric acid orally. Whereas, administration of ethanol extract at doses of 100 mg/kg bw did not decrease serum uric acid level significantly different compared to control group at hour 6 and 7 （P 〈 0.05）. Determination of uric acid level in urine, administration of ethanol extract at a dose of 200 mg/kg bw, or probenecid as a standard drug, at a dose of 45 mg/kg bw increased excretion of urine uric acid level significantly different compared to control group in day of 7 （P 〈 0.05） after inducing with potassium oxonate intraperitoneally simultaneously with uric acid orally. However, increase of uric acid excretion by ethanol extract was lower compared to that of probenecid at a dose of 45 mg/kg bw. Mechanism of action of the ethanol extract as an antihyperuricemia has been proposed by inhibition of xanthine oxidase and finally decreased the synthesis of uric acid and increased the excretion of urine uric acid level.

Effect of TongFengNing Decoction on Uric Acid Levels and Xanthine Oxidase Activity in Hyperuricemia Rats

Objective To observe the effect of TongFengNing Decoction （TD） on uric acid levels, xanthine oxidase （XOD） activity, and XOD mRNA expression of hyperuricemia （HUA） model rats. Methods： 90 rats were randomly divided into 6 groups （n=15）, and the HUA model in all groups except the blank group was established by administering hypoxanthine （HX） by gavage and injecting potassium oxonate （OAPS） intraperitoneally. Rats in all TD groups and allopurinol group were administered multiple doses of TD and a single dose of allopurinol by gavage twice daily for 21 days, while the blank group and the model group were administered normal saline. On the 7th, 14th, and 21st days of drug intervention, serum uric acid （SUA）, urine uric acid （UUA）, intestinal uric acid （IUA）, as well as XOD activity and mRNA expression in the liver and small intestine were measured in randomly selected 5 rats of each group. Results： On the 14th and 21st days of intervention, all TD dose groups and the allopurinol group showed decreased SUA and IUA levels, increased UUA levels, as well as decreased XOD activity and mRNA expression in the liver and small intestine, compared with the model group （P 〈 0.05）. The low- and high-dose TD group and the allopurinol group showed increased SUA and IUA levels, as well as XOD activity and mRNA expression in the liver and small intestine, and decreased UUA levels, compared with the moderate-dose TD group （P〈0.05）. Upon extending the drug intervention time of each TD dose group, SUA and IUA levels, XOD activity, and XOD mRNA expression in the liver and small intestine decreased and UUA levels increased （P 〈 0.05）. Conclusion： TD reduces SUA levels in HUA model rats, which promotes uric acid excretion and inhibits XOD activity and XOD mRNA expression to reduce uric acid production. The reduction in uric acid level by the intermediate dose of TD was better than that by allopurinol and the low and high doses of TD.

Uric acid lowering effect of Tibetan Medicine RuPeng15 powder in animal models of hyperuricemia

OBJECTIVE: To evaluate the influence of the Tibetan medicine Ru Peng15 powder(RPP15) on uric acid levels, and explore its possible mechanisms of action in hyperuricemic animal models.METHODS: Hyperuricemic mice were generated by orally administering yeast extract paste twice daily(30 g/kg) for 8 days, to mimic human hyperuricemia induced by high-protein diets. Hyperuricemic rats were generated by intraperitoneal injection of 250 mg/kg potassium oxonate to each animal 1 h before the last oral administration of test compounds, which raised the serum uric acid level by inhibiting the decomposition of uric acid. Levels of uric acid and creatinine in serum and urine were detected by the phosphotungstic acid and picric acid methods respectively, and the activity of xanthine oxidase(XOD) was assayed using a commercial test kit.RESULTS: RPP15(0.4, 0.8, 1.2 g/kg) significantly decreased the level of serum uric acid in healthy rats(P < 0.05). Furthermore, hyperuricemic rats treated with RPP15(0.4, 0.8, 1.2 g/kg) had lower serum uric acid levels(P < 0.05), accompanied by lower urine uric acid(P < 0.05). For the hyperuricemic mice, the levels of uric acid in the serum decreased significantly(P < 0.05) and the activity of XOD in the liver was restored to normal levels after treatment with RPP15(P < 0.05).CONCLUSION: RPP15(0.4, 0.8, 1.2 g/kg) demonstrated an anti-hyperuricemic effect on both healthy and hyperuricemic animals, and the mechanism is most likely associated with inhibiting the activity of XOD.