AIM To investigate the expression of pep-tide transporter (PEPT)2 mRNA in the lungs of ratswith lipopolysaccharide(LPS)-induced acute lung inju-ry. METHODS Health male Sprague-Dawley rats were divided randomly into 5 groups: normal control,cheally) given groups. Lung histopathological changes were observed under light microscope. Lung wet-to-dry weight (W/D) ratios, total protein concentration in bronchoalveolar lavage fluid (BALF) and lung my-eloperoxidase(MPO) activity were measured. The ex-pression levels of PEPT2 mRNA were evaluated by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS Typical pathological inflammation changes in the lungs, including alveolar congestion, hemorrhage, edema, infiltration of neutro-phils in the air space or vessel wall, thickness of the alveolar wall, and hyaline membrane formation, were observed in LPS groups. The lung W/D ratios in LPS 2, 4 and 8 h groups (4.72±0.18, 5.06±0. 17 and 5.12±0.16) were significantly higher than those innormal control and saline groups (4.12±0. 15 and 4.14±0.11). Compared with normal control and sa-g-1 wet tissue], MPO activity increased obviously in LPS2,4 and 8 h groups[(1.96±0.15), (2.23±protein concentration in BALF in LPS 2, 4 and 8 hgroups [ (36.6±2.9), ( 86.9±3.5 ) and (92.2±There was no statistical difference in PEPT2 mRNA levels in the lungs of rats among all groups. CON-CLUSION PEPT2 mRNA level does not change sig-nificantly in the acute injured lung tissue induced by LPS.

AIM To identify differentially expressed proteins in the plasma that may be used as biomarkers for heroin addiction through a two-dimensional (2-D)gel electrophoresis/mass spectrometry approach. METHODS Following removal of albumin and IgG,the plasma from 5 heroin abusers and 5 normal controls was separated by 2-D gel electrophoresis using immobi-lized pH gradients 4 -7 drystrip and PAGE. Gel ima-ges were analyzed using ImageMaster Elit 5.0. Differ-ential proteins were selected and analyzed through tan-dem mass spectrometry. RESULTS Average number for samples was 350±21 protein spots. In them there were 5 spots that differed by more than 1.5 fold be-tween the two groups obtained through image analysis.Through tandem mass spectrometry above spots were identified as fibrinogen γ (increased by 5 fold), hu-man α1-B-glycoprotein (decreased to 1/1.8 of control group), uncleaved α1-antitrypsin (increased by 2.5 fold), chain of transthyretin (decreased to 1/2 of con-trol group ) and ccruloplasmin (increased by 6.6 fold ). CONCLUSION There are differences between heroin abusers and normal controls in the blood plasma proteome. Some proteins may have a role in the damage to central nervous system through heroin abuse. Such proteins may provide novel biomarkers for diagnosis and therapeutic targeting, as well as clues forunderstanding the mechanism of heroin abuse.

AIM To investigate the tissue distribution of exendin-4 after administration in healthy rats. METHODS Exendin-4 was radioiodinated by the Iodo-GenTMmethod. Tissue distribution of [125I]exendin-4 was investigated after sc administration of [125I]exendin-4 at 3 μg·kg-1 in rats. Both total radioactivity and trichloroacetic acid (TCA) precipitated radioactivity were used to calculate the levels of [125I]exendin-4 in rats plasma and tissue samples after sc administration. RESULTS The tissue distribution of [125I]exendin-4 after sc injection showed substantial disposition in kidneys, lungs, bladder and pancreas. The rank order of normalized tissue distribution was kidneys＞lungs＞bladder＞pancreas＞intestine＞plasma＞adrenals>jejunum＞lymph＞liver＞spleen＞heart＞marrow＞thymus＞testicles＞brain＞muscle＞adipose. CONCLUSION [125I]Exendin-4 underwent a rapid and wide distribution in the tissues throughout the whole body within the time course examined. TCA precipitated radioactivity in kidneys was the highest, however, only trace amounts of [125I]exendin-4 was detected in the brain.

AIM The effects of GW501516, a peroxisome proliferator-activated receptor β (PPARβ) agonist, in long term diet induced obesity (DIO, high fat and maltose diet for 4 months) mice were evaluated, and the efficacy of GW501516 against insulin resistance and the involved mechanism was investigated. METHODSMice were divided into 3 groups: normal control, DIO model and DIO model+GW501516. GW501516 (10 mg·kg-1·d-1) was administered by ig once a day for 14 d. During the treatment, body weight and food intake were monitored every other day. The oral glucose tolerance test, and the serum biochemical parameters including the serum triglyceride, total cholesterol and high density lipoprotein cholesterol (HDL-C) levels were measured according to the specifications. To confirm the GW501516-mediated PPARβ activation, the mRNA levels of downstream genes related to glucose, lipid metabolism and energy expenditure was measured. RESULTS GW501516 treatment effectively improved the glucose intolerance, increased the area under the glucose curves[DIO model, (32.4±4.6) mmol·h·L-1 compared with DIO model+GW501516, (23.4±2.5) mmol·h·L-1, n=7-8, P<0.05], normalized the fasted blood glucose, and increased serum HDL-C level, besides, histological analysis revealed the decreased hepatic lipid accumulation and hypertrophy of hepatocyte in DIO mice. Moreover, RT-PCR results indicated that carnitine palmitoyltransferase 1b, uncoupling protein 2, uncoupling protein 3 and glucose transport protein 4 were all upregulated. CONCLUSIONGW501516 significantly ameliorates glucose intolerance, decreases fasted blood glucose and hepatic steatosis, which might be related to ① the enhancement of fatty acid oxidation and energy uncoupling in muscle, and ②the improvement of insulin-stimulated glucose transportation in skeletal muscle in the long term DIO mice.

AIM To investigate cyclin dependent kinase 9(Cdk9) and cyclin T1 protein expressions in diabetic rat kidney and the effect of berberine on them. METHODS Type 2 diabetes mellitus (T2DM) rats were induced by injection (ip) with diet for 16 weeks. From week 17 to 32, diabetic rats were given berberine 75, respectively. The kidney tissue structure was observed with hematoxylin/eosin (HE) staining, kidney to body weight ratio was calculated, and Cdk9 and cyclin T1 expressions were examined by immunohistochemistry. RESULTS Compared with control rats, the volume of diabetic model rat glomerulus accreted, some intercapillary cells proliferated and mesangial region expanded, both glomerular basement membrane and renal tubular basement membrane thickened. Treatment with diabetic nephropathy symptom. The diabetic kidney to body weight ratio protein expressions in diabetic kidney to near control level. CONCLUSION Berberine regulates Cdk9 and cyclin T1 protein expressions in diabetic kidney which may partly contribute to ameliorate nephropathy complication induced by STZ and the high-carbohydrate/high-fat diet.

AIM To study whether chronic administration of methylamine may induce elevation of semicarbazide-sensitive amine oxidase (SSAO) activity and initiate the injury of cardiovascular endothelium. METHODS New Zealand rabbits were treated with methylamine hydrochloride (100 mg·kg-1) by ig, once a day for 6 months. The rabbits were weighed every other week and the dosage was adjusted according to the body weight. The number of circulating endothelial cells (CEC) in the arterial blood, nitric oxide (NO) concentration in the serum and ultrastructure of endothelial cells of aorta were assessed. The plasma SSAO activity and formaldehyde concentration were assessed by liquid chromatography. RESULTS The number of CEC, NO concentration, levels of SSAO activity and formaldehyde concentration in the methylamine group were increased significantly, compared with the control group. Ultrastructure of endothelial cells in the methylamine group showed inordinate morphological changes (multiple intranuclear inclusions, karyopyknosis and karyorrhexis). CONCLUSIONChronic administration of methylamine can induce the elevation of SSAO activity and initiate the injury of cardiovascular endothelium.

AIM To investigate whether ginsenoside Rg1 can reverse chronic lead-induced impairment of long-term potentiation (LTP) in the CA1 region of rat hippocampus. METHODS Neonatal Wistar rats were exposed to lead from parturition to weaning via milk of dams whose drinking water (20 mL per day) contained 0.2% lead acetate. Field excitatory postsynaptic potentials (fEPSP) were recorded and LTP was induced in the CA1 region in rat hippocampal slices on postnatal 20-25 d. RESULTS In hippocampal slices from both control and lead-exposed rats, perfusion with ginsenoside Rg1 50 μmol·L-1 for 20 min induced enhancement of fEPSP (LTP), while the amplitude of LTP in lead-exposed rats was lower than that of controls. In hippocampal slices from chronic lead-exposed rats, LTP induced by high-frequency stimulation (HFS, 1s, 100 Hz) was significantly reduced, while perfusing with ginsenoside Rg1 (50 μmol·L-1) for 20 min increased the amplitudes of LTP induced by HFS by 47.1%. CONCLUSION Rg1 can increase basic synaptic transmission and partially reverse chronic lead-induced impairment of HFS-LTP.

AIM To investigate the role of serine/threonine protein phosphatases 1 and 2A (PP1/2A) in regulation of cell signal transduction involved in the tolerance of human umbilical vein endothelial cells (HUVEC) to hypoxia. METHODS HUVEC tolerance was established by hypoxic preconditioning. The tolerance of HUVEC was evaluated by the cell survival rate, lactic dehydrogenase (LDH) releasing and total antagonistic-oxidative capability (T-AOC). Subcellular localization of nuclear factor E2-related factor 2 (Nrf2) was determined by immunocytochemistry combined with Western blot. The expression of stress protein of heme oxygenase-1 (HO-1) was measured by Western blot. RESULTS Hypoxia 90 min decreased the survival rate and T-AOC of HUVEC significantly, increased the release of LDH in cultured HUVEC. Compared with the hypoxic group, hypoxic preconditioning (4, 8 and 24 h after hypoxia 10 min) up-regulated the tolerance against hypoxia in HUVEC, the survival rate of HUVEC and T-AOC increased and the release of LDH down-regulated when insulted with hypoxia (90 min) in HUVEC. Hypoxic preconditioning established the translocation of Nrf2 from cytoplasm to nucleus and up-regulated the expression of downstream protein HO-1. Pretreatment with okadaic acid (40 nmol·L-1), a powerful inhibitor of PP1/2A, for 10 min in hypoxic preconditioning HUVEC partly inhibited the translocation of Nrf2 from cytoplasm to nucleus and the expression of HO-1, abolished the tolerance of HUVEC established by hypoxic preconditioning. CONCLUSION PP1/2A at least partly take part in Regulation of translocation of Nrf2 and expression of HO-1, with is associated with the tolerance of HUVEC established by hypoxic preconditioning.

AIM Xiaobuxin-Tang (XBXT) is a traditional Chinese herbal decoction which is composed of Haematitum, Flos Inulae, Folium Phyllostachydis Henonis and Semen Sojae Preparatum. The present study was to investigate if the total flavonoids extracted from XBXT (XBXT-2) had antidepressant effect. METHODS Forced swimming tests in mice and rats, and learned helplessness (LH) model of rats were adopted to affirm the antidepressant effect of XBXT-2 with the test on spontaneous motor activity. Plasma corticosterone level in the LH rats was measured with ELISA. RESULTS Single administraton of XBXT-2 at the doses of 50 and 100 mg·kg-1 (ig) significantly decreased the duration of immobility time in the forced swimming tests in mice and rats. Researches on LH model of rats indicated that XBXT-2 at doses of 50 and 25 mg·kg-1 markedly reduced the number of escape failure in shuttle box. Meanwhile, the plasma corticosterone level of the LH rats was significantly decreased. XBXT-2 50-200 mg·kg-1 had no effects on spontaneous motor activity in mice. CONCLUSION XBXT-2 possesses significant antidepressant-like effect. The mechanism may involve the inhibition of the hyperaction of the hypothalamic-pituitary-adrenal axis.

AIM To evaluate the value of arsenic trioxide (ATO) in the treatment of systemic lupus erythematosus and to investigate its mechanism. METHODS① Thirty four BXSB lupus mice were averagely and randomly divided into ATO treated group and control group. The mice of ATO treated group were given (ip) ATO 0.4 mg·kg-1 every other day until d 105 and the observation was ended on d 210. The survival rate of mice was recorded, and the levels of serum IgG and anti-dsDNA antibody were measured with enzyme-linked immunosorbent assay. ② Other 20 BXSB lupus mice were also divided into 2 groups and treated as above and sacrificed on d 90. The spleen and kidneys of each mouse were removed and total RNA was extracted. The levels of interferon-γ (IFN-γ) mRNA in renal and spleen tissues were measured by using reverse transcription polymerase chain reaction. RESULTSUp to d 210, 8 mice died in ATO treated group and 13 died in control group. On d 90 and d 105, the average levels of serum anti-dsDNA antibody (A450 nm) were (0.335±0.011) and (0.223±0.017) in ATO treated group, and (0.688±0.016) and (0.683 ±0.014) in control group. On d 90, the expressions of IFN-γ mRNA in spleen and renal tissues of ATO treated group were significantly lower than that of control group. On d 105, the serum level of IgG was much lower in ATO treated group than that in control group, which were (4.9±1.3) and (6.9±1.0)g·L-1, respectively. CONCLUSION ATO elevates the survival rate, lowers the serum levels of IgG and anti-dsDNA antibody, and depresses the expression of IFN-γ mRNA in spleen and kidney tissues of BXSB mice.