AIM To investigate the effects of the novel compound pivanampeta on the fatty liver induced by cholesterol-feeding in rabbits and quails. METHODS ①24 male rabbits were divided into four groups randomly as following: control group, model group, pivanampet 1 and 5 mg?kg -1 groups. The serum levels of total cholesterol were determined after the rabbits were cholesterol-fed for 12 weeks. The morphological changes of liver were observed. The levels of cholesterol and malonal-dialdehyde and the activities of glutatione peroxidase in the homogenate of liver were also measured.②181 male quails were divided into six groups randomly:control group, model group, Simvastatin 5 mg?kg -1 group, pivanampet 3,6 and 9 mg?kg -1 groups. The serum levels of total cholesterol were determined after the quails had been fed with cholesterol diets for 11 weeks. After 14 weeks part of the animals were killed, the morphological changes of liver were observed. The hepatic coefficient were determined after the remaining quails were cholesterol-feeding for 18 weeks. RESULTS Pivanampet alleviated the liver Steatosis induced by cholesterol-feeding in rabbits and quals. It decreased total cholesterol levels, elevated the activity of glutatione peroxidase in the rabbits liver, and reversed the increasing hepatic coefficient in rabbits and quails. CONCLISION The novel compound Pivanampet can delay the formation of fatty liver by cholesterol-feeding.

Due to the completion of human genome project and the advent of new technologies, the traditional drug discovery is shifting to genomics-based drug discovery. Target discovery is an important first step in drug discovery pipeline. In this review, we critically introduce the strategies and biology technologies for target discovery, especially focus on the likely impact of new technologies in drug target research and speculate the future trend of target research.

Objective To observe the effects of 1,3-dipropyl-8-cyclopentylxanthine(DPCPX),an adenosine A1 receptor antagonist,on brain neurons damage induced by hypoxia and reoxygenation(H/R),and to elucidate the relevant mechanisms.Methods An in vitro cultured rat cerebral cortical neuronal H/R damage model was established;the effects of DPCPX were detected at final concentrations of 0(control),25,50,100nmol/L on the lactate dehydrogenase(LDH) release from normoxic neurons and H/R neurons which were treated with hypoxia for 8,12,24 hours followed by reoxygenation for 24 hours;the changes of malondialdehyde(MDA) content,activities of xanthine oxidase(XO) and Ca2+-ATPase in H/R neurons which were treated with hypoxia for 12 hours and reoxygenation for 24 hours brought by administration of DPCPX at the concentration of 100nmol/L were also determined by use of specific reagents.Results With addition of 100nmol/L DPCPX,the LDH release from H/R neurons which were treated with hypoxia for 12 hours and reoxygenation for 24 hours was significantly increased compared with that in control group(P

There is another factor involving in endothelium dependent relaxation besides NO, which is independent of cGMP, EDHF. Its hyperpolarization mechanism may be related to the open of calcium dependent K + channels(K + Ca). NO, PGI 2,H 2O 2 and cytochrome P450 derived metabolite of arachidonic acid are all the candidates of EDHF. In the normal blood vessels, the influence of EDHF on endothelium dependent relaxation is little. But in some diseases, when the production and effect of NO is disturbed ,the mechanism of EDHF may play a specially important role.

It is well documented that vascular tone is the key determinant of blood vessel resistance and blood flow. But vascular tone could be regulated by modulating the activity of potassium channel directly. Potassium channel openers promote vasodilation by inhibiting the activity of voltage dependent calcium channels and reducing Ca 2+ influx. In this case, inhibition results from membrane hyperpolarisation, which arises due to the stimulation of K + efflux through smooth muscle K + channels. While K + channels are blocked, vasoconstriction could be observed as a result of membrane depolarization, which opens voltage dependent calcium channels. The influx of Ca 2+ can promote smooth muscle contraction by making myosin light chain phosphorylation and arising thick myofilament and thin myofilament relative movements. In this article, the gene structure, current character, Pharmacological and physiological effects of the four subtypes potassium channels are reviewed.

The functions of vascular endothelial cells (VEC) are closely related with the etiology of cardiovascular diseases. The present paper reviews the bioactive substances secreted from endothelial cells and their regulatory effects on the tone of blood vessel wall, on the functions of platelet adhesion and aggregation, on the hemostatic and fibrinolytic systems.

ATP sensitive potassium (K ATP ) channels widely expressed in many tissue and cell types including neurons are heteromultimers of sulfonylurea receptor (SUR) and inward rectifier K + channel (Kir6) subunits associated with 1∶1 stoichiometry as a tetramer (SUR/Kir6) 4. The activity of K ATP channels is modulated by intracellular ATP concentrations. Neuronal K ATP channels are involved in the mediation of glucose sensing and metabolic stress. Under physiological condition, they also possess important pathophysiological functions in acute brain ischemic and chronic neurodegenerative diseases.

Objective To investigate the preventive effect of iptakalim hydrochloride(Ipt) on brain edema in rats after exposure to simulated high altitude and the mechanisms involved.Method Adult Wistar rats were randomly divided into normoxic control group,simulated plateau acute hypoxia group simulated 8 000 m for 8 h and three Ipt taking groups which were pretreated with 2, 4 and 8 mg(kg?d) of Ipt respectively for 7d before exposure to hypoxia.Water content was determined by the wet-dry method;Na~+,K~+,Ca~(2+) and Mg~(2+) content in the cortex was detected with all atomic absorption spectrophotometer;inorganic phosphorus standardization was applied to decide the activities of Na~+/K~+-ATPase,Ca~(2+)-ATPase and Mg~(2+)-ATPase;Occludin and AQP4 gene expression were determined by RT-PCR.Result The water content was increased and the concentration of Na~+ and Ca~(2+),the activities of Na~+/K~+-ATPase,Ca~(2+)-ATPase and Mg~(2+)-ATPase and the gene expression of the Occludin and AQP4 were all down-regulated in acute hypoxia group compared with normoxic control group.And these changes could be significantly relieved by pretreatment with Ipt.Conclusion Ipt can prevent the occurrence of brain edema caused by acute hypobaric hypoxia possibly related to the effect on water content,electrolytes concentration,ATPase activity and gene expressions of aquaporin and tight junction proteins.

ATP sensitive potassium channels (K ATP ) have been thought to be a mediator of cardioprotection. Recent pharmacologic and molecular biology studies show the protective effects of K ATP openers are not dependent of action potential shortening and cardiodepressant effects, but mediated by preservation of mitochondrial function, which suggests a role for intracellular mitochondrial K ATP (mito K ATP ). The mechanism by opening mito K ATP produces cardioprotection is less clearer, however, it is thought that a beneficial effect may occur as the result of K + entry and intramitochondrial depolarization. This effect would reduce mitochondrial calcium overload and cause matrix swelling, which are shown to enhance ATP synthesis and stimulate mitochondrial respiration.

AIM To investigate the protective effects of iptakalim hydrochloride (Ipt) against glutamate induced neurotoxity. METHODS Neurotoxity injury was induced by with glutamic acid in PC12 cells. The cell viability was measured by MTT assay. RESULTS Ipt at the concentrations of 1 ? 1(T-10 - 1 ? 1(T4 mol ? L-1 markedly mitigated glutamate-induced neurotoxicity. The protec- live effect was nullified by glibenclamide, an ATP-sensitive potassium channel antagnist. CONCLUSION Ipt provides neuroprotection on glutamate-induced cytotoxixity in cultured PC12 cells and this effect may be related with ATP-sensitive potassium channels.