The abnormal expression of gastrins and their receptors have close relationship with the occurrenceand the development of some colorectal neoplasms.The high expression of gastrins and their receptors promote colorectal neoplasms cell proliferation and inhibit apoptosis.The biological behavior is mainly rely on the abnormal expression of protein.Using differential proteomics can screen differential expression protein of high expression of gastrin-based colorectal neoplasms in the occurrence and development process,and then with the regulation of specific proteins to achieve the prevention and treatment of colorectal neoplasms purposes.

Aim To investigate the effect of dehydroepiandrosterone(DHEA)on the levels of NR2B and GBR1 expressed in primary cultured rat cerebral cortical neurons.Methods Primary cultured rat cerebral cortical neurons were treated with DHEA of different concentrations (1,10,100 μmol·L~(-1))and the expression of amino acids receptor subunit NR2B and GBR1 were detected by immunocytochemistry.Results Compared with control group,the expression intensity of NR2B increased by 15.6%,19.9% and 49.4% after DHEA-L,DHEA-M and DHEA-H treatment(P<0.05 or P<0.01);the expression intensity of GBR1 increased by 14.5% and 58.5% after DHEA-M and DHEA-H treatment(P<0.05 or P<0.01).Conclusion DHEA can enhance the expression of neuron receptor subunit NR2B and GBR1.

Objective To investigate the effects of morphine dependence and withdrawal on neurosteroids and amino acid transmitters of rat amygdala. Methods Morphine dependence was induced by pretreatment with increasing doses of morphine for 7 days. Withdrawal was precipitated by naloxone (2mg/kg). Withdrawal syndromes were observed and scored. After decapitation, amygdala was dissected out. Nomadic and conjugated neurosteroids were extracted using liquid-liquid extraction and solid phase extraction. Concentrations of neurosteroids including dehydroepiandrosterone (DHEA), pregnenolone (PREG), allopregnanolone (AP), dehydroepiandrosterone sulfate (DHEAS) and pregnenolone sulfate (PREGS) were detected with HPLC-MS. Concentrations of glycine (GLY), glutamate (GLU) and gamma-aminobutyric acid (GABA) were quantitated by HPLC-ECD with pre-column OPA derivatization. Results Compared with saline control, the DHEA level in rat amygdala of morphine dependent group decreased by 33% (P＜0.01). Compared with naloxone control, the PREG and AP levels in rat amygdala of morphine withdrawal group increased by 45% (P＜0.05) and 42% (P＜0.05) respectively; the GABA level decreased by 18% (P＜0.01). Compared with morphine dependent group, the PREG and PREGS levels in rat amygdala of morphine withdrawal group increased by 60% and 40% respectively (P＜0.05); the glycine level decreased by 14% (P＜0.05). Conclusion The DHEA in rat amygdala may play a role in the development of morphine dependence but not involved in the manifestation of withdrawal symptoms. Other neurosteroids (including PREG, AP and PREGS) in rat amygdala seem to be involved in withdrawal but not in dependence. The synthesis and release of inhibitory amino acids in amygdala were depressed when withdrawal was precipitated by naloxone. The results suggest that different changes of neurosteroids and amino acids exist in stages of morphine dependence and withdrawal.

Objective: To investigate the effect of morphine dependence and withdrawal on the levels of neurosteroids in hippocampus of male rat.Methods: Rats were given (ip) increasing doses of morphine to form morphine physical dependence, withdrawal syndromes were precipitated by naloxone. The conditioned place preference (CPP) was used to establish morphine psychological dependence. The concentrations of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), pregnenolone (PREG), pregnenolone sulfate (PREGS), and allopregnanolone (AP) in rat hippocampus and plasma were quantified by liquid chromatography-mass spectrometry. Results:The rat model of morphine physical and psychological dependence were successfully established by ip increasing doses of morphine for 7 days and 5mg?kg~ -1 morphine for 10 days respectively. Compared with saline control group, morphine physical dependence increased DHEA and PREG contents in rat hippocampus (0.88?0.19/0.67?0.17,t=2.52,10.94?2.02/7.53?2.64,t=3.24,P

Aim To investigate the effects of progesterone on morphine rewarding effect and levels of endogenous opioid peptides in hypothalamus of rat brain. Methods Conditioned place preference(CPP)test was used to investigate the morphine rewarding effect, and radioimmunoassay (RIA) was established to deter-mine levels of ?-endorphin(?-EP), leu-enkephalin(L-EK) and dynorphin A(DynA) in hypothalamus of rat brain.Results Compared with NS control group, 5 mg?kg-1 morphine successfully induced the formation of CPP(P

Aim To investigate the effect of progesterone on the levels of glutamate and ?-aminobutyric acid released from primary cultured rat cerebral cortical neurons.Methods Primary cultured rat cerebral cortical neurons were treated with PROG(10 ?mol?L-1) and the concentrations of amino acid in cell culture media at different time(0.5,1,1.5,2,24,36,48,72 h) were measured by OPA-mercaptoethanol precolumn derivatization technique and HPLC-FLD.Results Compared with control group,PROG treatment significantly reduced the levels of GLU at the time of 1,1.5,2,24,36,48,72 h(P

Aim To detect the effect of morphine dependence and withdrawal on the levels of neurosteroids and amino acid neurotransmitters in nucleus accumbens in rat morphine dependent model. Methods Nucleus accumbens was dissected out from morphine dependent and naloxone precipitated withdrawal rats. The contents of neurosteroids including dehydroepiandrosterone, pregnenolone, allopregnanolone, dehydroepiandrosterone sulfate and pregnenolone sulfate were detected with liquid chromatography-negative atmospheric pressure with ionization mass spectrometry(LC-MS). The contents of glycine, glutamate and ?-aminobutyric acid were quantitated by HPLC-ECD with precolumn derivatization. Results Compared with saline group,in nucleus accumbens of morphine withdrawal rats, the level of dehydroepiandrosterone sulfate (P

AIM To investigate if morphine addiction and relapse to morphine-seeking is related to the change in neurosteroid levels in the brain of rats. METHODS Rats were injected ip morphine (5 mg·kg-1·d-1, 18:00-20:00) and trained in conditioned place preference (CPP) box, once daily for 10 d. CPP test was performed 24 h after the last training. After discontinuation of training for 7 d for CPP extinction, then intermittent and inescapable foot-shock (FS, 0.5 mA, 0.5 s on, 40 s off, 15 min) was applied to rats as the priming stimuli for relapse. CPP test was performed 2 h after FS. When CPP test finished, rats were decapitated and the levels of neurosteroids were analyzed using gas chromatography/mass spectrometry. RESULTS CPP was established when rats were injected morphine and trained for 10 d. At the same time, the levels of pregnenolone and allopregnanolone in the brain tissues of rats were significantly increased. When CPP was reinstated in morphine-treated rats by FS-stress after 7 d CPP extinction, the levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate were significantly increased. CONCLUSIONThe development of morphine addiction and relapse may be related to endogenous neurosteroids in rat brain tissues.

Aim To investigate the protective effect of naringenin on isoniazid and rifampicin induced hepatotoxicity and the role of CYP 3A4.Methods Isoniazid and rifampicin were added to culture media for QSG-7701 cells and cultured for 48 hours. Narringenin, 1,5 and 25 mg·L~(-1) in final concentration,was added concomitant with isoniazid and rifampicin. The culture media and cells were collected and the activities of lactate dehydrogenase were detected with chromatometry. The ratio of extra/intracellular lactate dehydrogenase was calculated as the release rate of lactate dehydrogenase. Cells were incubated with midazolam for 2 hours after treatment with durgs and the concentration of midazolam in the incubation media was determined with HPLC-MS.Results Compared with control group, isoniazid and rifampicin treatment increased lactate dehydrogenase release and CYP 3A4 activity significantly. Naringenin attenuated the effect of isoniazid and rifampicin on lactate dehydrogenase and CYP 3A4 activity.Conclusion Naringenin can attenuate the hepatotoxicity of isoniazid and rifampicin through inhibiting the activity of CYP 3A4 in cultured hepatocytes.

Objective To investigate the mechanisms of the protective effects of dexmedetomidine against the propofol-induced neuroapoptosis in primary cultured cortical neurons.Methods The neurons were cultured 7days and then divided into four groups: vehicle-control group (treated with equal volume of intralipid), propofoltreated group (treated with 500 μmol/L propofol), propofol plus dexmedetomidine treated group (treated with 500 μmol/L propofol and 0.1 μmol/L dexmedetomidine), and LY294002 pretreated group (treated with 500 μmol/L propofol ,0.1 μ mol/L dexmedetomidine and 10 μmol/L LY294002).12 hours after different treatments, neuron viability was measured by MTT assay,neuroapoptosis was detected by Hoechst33258 staining, and the levels of pAkt and Bcl-2 protein were detected by Western blot.Results Compared with the vehicle-reduced group,propofol reduced neuron viability greatly((53.4±4.2)％ vs (99.9±6.3)％;P＜0.01), but increased neuroapoptosis greatly((44.6±4.3)％ vs (5.8±0.4)％;P＜0.01).The levels of pAkt((0.41±0.03) vs (0.86±0.07))and Bcl-2 ((0.15±0.02) vs (0.72±0.03)) were decreased greatly (both P＜0.01).Compared with propofol treatment group, the neuron viability of propofol plus dexmedetomidine group were increased greatly((86.4±5.3) ％ , P＜0.01) ,the neu roapoptosis was decreased greatly ((23.1 ± 3.5) ％, P＜ 0.01), and the levels of pA kt (0.8 ± 0.03) and Bc1-2 (0.52 ±0.05) were increased greatly (both P＜0.01).Compared with propofol plus dexmedetomidine treated group,LY294002 inhibited the protective effects of dexmedetomidine, decreased neuron viability greatly ((64.3±5.1) ％ ,P＜0.01), increased the number of apoptotic neurons((38.8±4.9) ％, P＜0.01), and reduced the levels of pAkt (0.52±0.04) and Bcl-2(0.31±0.02) significantly (P＜0.01).Conclusion Dexmedetomidine exerts the neuroprotective effects against propofol-induced neuroapoptosis by activating the PI3K-Akt-Bcl-2 signalling pathway.