PPAR ? is one of the three isoforms of peroxisome proliferator-activated receptors (PPARs) which are essential regulators of lipid storage and metabolism. PPAR ? primarily stimulats lipid metabolism and energy uncoupling in adipocytes and myocytes as well as involvs in the onset and development of many diseases. As the target of medicines, PPAR ? agonists may be powerful drugs for epidermal wound and metabolic syndrome X.

Peroxisome proliferator-activated receptors (PPARs)are ligand-activated nuclear tran-scription factors,playing an important role in the regulation of glucose and lipids metabolism,inflamma-tion response,proliferation and differentiation.Some drugs targeted on PPARs,such as lipid-lowering and antidiabetic drugs have been developed.Some PPAR agonists were found carcinogenic in animal experi ments,including PPAR αagonist fibrates,PPARγagonist thiazolidinediones,PPARα/γdual ago-nist compounds,and PPARδagonist compounds for clinical development.PPARαagonist carcinogenicity is associated with PPAR receptor activation that regulates lipid metabolis m,and leads to lipids abnormali-ties and increase by peroxisome oxidase in reactive oxygen species (ROS),causing DNA damage. Kupffer cells can generate ROS by NAD PH oxidase that pro motes hepatocyte proliferation and inhibition of apoptosis.PPARγagonist carcinogenicity is generally caused by bladder stone.The carcinogenicity of PPAR agonists to humans has not been confirmed,but the carcinogenic potential of these drugs can-not be ignored.

, 15min),the clearance of reticuloendothelial system (RES) of mice on iv charcoal particles were decreased apparently; serum hemolysin concentration were diminished notably; delayed type hypersensitivity (DTH) reaction induced by sheep red blood cell (SRBC) were inhibited obviously. Ginseng root saponins (GRS) 50, 100 mg ??? kg-1ip at 15min before the heat-stressprotected the immunity of mice from inhibitory effects induced by the heat-stressor. The suppression of the clearance of RES on charcoal particles,serum hemolysin concentration as well as DTH reaction induced by SRBC were all abolished by GRS.

Objective To study the antidepressant effect of total timosaponin(TT)and its mechanism.Methods The antidepressant effect of TT was examined by mice forced swimming test(FST),learned helplessness(LH)experiment,chronic mild stress(CMS)model,yohimbine induced lethality test and 5-HTP induced head-twitches test.Results TT(25 or 50 mg?kg-1,ig,qd?14 d)markedly shortened the immobility time in the FST,but didn't affect the autonomic activity.TT(12.5,25 or 50 mg?kg-1,ig,qd?14 d)significantly decreased the number of escape deficits in the LH mice.TT(25 or 50 mg?kg-1,ig,qd?21 d)markedly enhanced the locomotor activity and increased consumption of sucrose solution in CMS mice.TT(50 mg?kg-1,ig,qd?14 d)enhanced the mortality of mice after administration of yohimbine for 4 h,and distinctly increased the head-twitch number in the 5-HTP induced head-twitches test.Conclusion TT has antidepressant effects in various depression mouse models.Its mechanism may be related to the reinforcement of NE and 5-HT nerves system.

Aim To study the mechanisms of N-demethyl-clarithromycin-induced apoptosis in human cervical cancer cell line HeLa. Methods MTT, photomicroscopical observation, DNA agarose gel electrophoresis, LDH release and Western blot were used for apoptosis assay. Results N-demethyl-clarithromycin inhibited growth of HeLa in a time-dependent manner. Apoptotic bodies were found with Hoechst 33258 staining after treatment with 60 ?mol?L-1 N-demethyl-clarithromycin. DNA fragmentation was observed in N-demethyl-clarithromycin treated HeLa cells. The Akt inhibitor and the ERK inhibitor (PD98059) increased cell death. The expression of anti-apoptotic protein Akt, phosphorylated-Akt, ERK and phosphorylated-ERK decreased. Conclusion N-demethyl-clarithromycin induces HeLa apoptosis through Akt and ERK expression and phosphorylation.

The peripheral blood T- lymphocyte percentage, lympocyte percentage in white blood cell (WBC) of mice in heat environment (45C, 15 min) were diminished, and serum corticosterone increased. Ginseng root saponins (GRS) 50, 100 mg/kg were administered ip at 15 min before the heat-stress, the suppression of peripheral blood T-lymphocyte percentage were prevented, but could not inhibit the increase ofserum corticosterone. GRS 50mg?kg-1ip could inhibit the redution of peripheral lymphocyte percentage. GRS 50mg?kg-1 ,reserpine 0.5mg? kg-1or physostigmine salicylate 0.3 mg?kg-1ip abolished the inhibiting effect of heat-stress on DTH reaction in mice.

Objective:Clonidine,by activating peripheral α-sbrenoceptors, produces transient pressor response after i.v.injection in anesthetized animals.Moxonidine, with at least 40-fold higher affinity to I1-imidazoline receptors than to α2-adrenoceptors,produces also a transient pressor response. This work was designed to investigate whether I1-imidazoline receptors are involved in this pressor effect of moxonidine. Methods:Female spontaneously hypertensive rats(SHRs,aged 14-16 weeks)were anesthetized with urethane.To observe the transient pressor responses,moxonidine 0.1,0.3,1.0mg/kg(intravenous,i.v),2.0μg(intracerebroventricular,i.c.v.)and 1.0,10.0mg/kg(intragastric,i.g.)were administrated in different groups of rats.To evaluate the roles of α1-adrenoceptors,α2-adrenoceptors and I1-imidazoline receptors in the transient pressor responses to moxonidine, prazosin(10.0μg/kg),yohimbine(2.0mg/kg),phentolamine(0.2mg/kg),idazoxan(1.0mg/kg)or yohimbine+idazoxan(2.0mg/kg+1.0mg/kg)were intravenously given to the animals before moxonidine 0.3mg/kg (i.v.).Results:It was found that i.v.moxonidine produced a greater pressor response than clonidine when producing a similar reduction of blood pressure.This effect of moxonidine was not influenced by prazosin, but was partly inhibited by yohimbine, phentolamine or idazoxan,and completely blocked by the combination of yohimbine and idzaxon.Neither i.c.v.injection nor i.g. administration of moxonidine induced transient pressor responses.Conclusion:The transient pressor response of i.v. moxonidine is mediated by both peripheral I1-imidazoline receptors and α2-adrenoceptors.

Objective To evaluate the repeated dose toxicity of MNT-016 in SD rats and to provide reference for toxicity evaluation.Methods MNT-016 was administered to rats at 5, 20 and 80 mg/kg for 90 days.The toxic effects on the animals were evaluated by observing the clinical signs and measuring the body weight, hematology and blood biochemistry as well as histopathological examination.NOAEL and benchmark dose lower confidence limit(BMDL) were observed by the end point of toxicity.Results Compared with the control group, the AST, TBIL, DBIL and Crea of male rats were increased in a dose-dependent manner, while TG and CHOL decreased.The body mass(before anatomy), heart, liver, thymus, epididymis of male rats in 80 mg/kg group were significantly decreased (P<0.05), while absolute organ mass of the heart and lung was increased.The body mass (before anatomy) and thymus of female rats in 80 mg/kg group were significantly decreased (P<0.05), while absolute organ mass of lungs was increased.Vacuolation of hepatocytes was observed in groups each dose, tubule atrophy was found in the kidneys of 20 and 5 mg/kg groups, and tubule basophilia was observed in 80 mg/kg group.The incidence of the above lesions was higher in male animals than in female ones.Conclusion The NOAEL of MNT-016 is lower than 5 mg/kg in male rats and 5 mg/kg in female rats.BMDL value is 2.65 mg/kg in male animals and more accurate than NOAEL, and is 9.04 mg/kg in female animals,which is slightly larger than the corresponding NOAEL.

Objective To investigate the effect of noninvasive positive pressure ventilation treatment on patients with acute left heart failure and hyoxemia.Methods Sixty-two patients with acute left heart failure and hyoxemia were divided into control group (31 cases) and treatment group (31 cases).All patients were treated with a conventional therapy plan and patients in treatment were received noninvasive positive pressure ventilation beside conventional therapy.Blood gas analysis,plasma B-type natriuretic peptide (BNP) and clinical manifestation before and after treatment were monitored.Results The time of clinical manifestation al0leviation in treatment group was (33.7 ±7.9) min,shorter than that of control group ((55.9 ± 12.1) min,t =8.554,P ＜0.01).Compared with pre-treatment,heart rate (HR),respiratory rate(RR),mean arterial pressure(MAP),pH,oxygen saturation of blood (SaO2),arterial partial pressure of oxygen (PaO2),arterial partial pressure of carbon dioxide(PaCO2) and BNP in treatment group were improved significantly(HR:(133.89 ± 5.45) beat/ min vs.(87.27 ± 5.74) beat/min,t =32.794,P ＜ 0.01 ; RR:(34.25 ± 5.67) beat/min vs.(20.15 ± 2.54) beat/min,t =12.636,P ＜ 0.01 ; MAP:(104.52 ± 7.25) mmHg vs.(76.57 ± 3.76) mmHg,t =19.055,P ＜0.01; pH:(7.29±0.06) vs.(7.40 ±0.06),t=7.218,P＜0.01;SaO2:(81.52 ±5.01)％ vs.(97.16±1.27) ％,t =16.848,P ＜ 0.01 ; PaO2:(55.30 ± 7.14) mmHg vs.(92.80 ± 6.24) mmHg,t =22.019,P ＜0.01;PaCO2:(46.23 ±10.30) mmHg vs.(40.56 ±5.19) mmHg,t =2.737,P＜0.05;BNP:(831.59 ±292.65) ng/L vs.(265.52 ±65.39) ng/L,t =10.511,P ＜0.01).And after treatment,HR,RR,MAP,SaO2,PaO2,BNP in control group were improved compared with that before treatment (HR:(132.13 ± 5.31) beat/min vs.(92.15 ± 4.28) beat/min,t =32.638,P ＜ 0.01 ;RR:(34.96 ± 4.78) beat/min vs.(23.91 ± 3.27) beat/min,t=l0.634,P＜0.01;MAP:(102.56 ±7.14) mmHg vs.(82.83±3.52) mmHg,t =13.800,P＜0.01;SaO2:(82.15 ± 5.24) ％ vs.(93.16 ± 2.59) ％,t =10.488,P ＜ 0.01 ; PaO2:(54.56 ± 6.27) mmHg vs.(75.19 ±3.52) mmHg,t =15.974,P ＜0.01 ;BNP:(823.15 ±277.26) ng/L vs.(371.15 ±87.55) ng/L,t =8.656,P ＜0.01).Statistical differences of pH and PaCO2 were not found in the control group before and after treatment(pH:7.32 ± 0.05,t =1.426,P =0.159 ;PaCO2:(43.78 ± 6.74) mmHg,t =0.253,P =0.801).HR,RR,MAP,pH,SaO2,PaO2,PaCO2 and BNP in treatment group were more significantly improved than that of control group(t =3.795,5.056,6.767,5.703,7.721,13.686,2.107 respectively,P ＜ 0.01or P ＜ 0.05).Conclusion The therapy plan of noninvasive positive pressure ventilation on patients with acute left heart failure and hyoxemia can improve cardiac function and oxygenation quickly,and decrease the plasma BNP level.