1.Adult zebrafish as a model organism for assessing the effects of hallucinogenic drugs on behaviors
Hui YAN ; Ruibin SU ; Zehui GONG
Chinese Pharmacological Bulletin 2014;(10):1464-1468
Aims To establish several behavioral paradigms to characterize the psychotropic effects of hallucinogens which ze-brafish was utilized as a model animal, and then to investigate the effects of potent hallucinogenic drugs on these models. Methods With the video record and track system, the behavior was recorded and quantified automatically. In the experiments, the bottom dwelling test, social behavior and mirror test were performed to test the hallucinogenic effects of drugs. Metham-phetamine (METH, 2 mg·L-1) and ketamine (20 mg·L-1) were selected as experimental challenges. The 30 min pre-treat-ment time was chosen based on our prior experience in zebrafish models. Results Compared to the normal group, in dwelling test, acute exposure of zebrafish to METH and ketamine de-creased transitions significantly, and in mirror reflection test, the drug-treated fish changed the preference for mirror zone, and ex-hibited aggressive for their mirror images. The pretreatment of METH and ketamine significantly reduced the contact durations, and the ketamine inhibited the contact frequency each other, the results indicated that the social interaction of zebrafish was im-paired. Conclusion The results confirm high sensitivity of ze-brafish models to hallucinogenic compounds with complex behav-ioral and physiological effects.
2.The function of C-terminal tail of opioid receptors and the proteins interaction with C-terminal tail of opioid receptors
Peilan ZHOU ; Lingdi YAN ; Zehui GONG
Chinese Pharmacological Bulletin 2003;0(08):-
The C-terminal tail of opioid receptor is important for opioid receptor phosphorylation,desensitization and internalization after opioid agonists treatment.The C-terminal point mutant and truncated mutant of amino acid residues of ?opioid receptors such as T394A,T383A,T357A,S355A affect the function of the opioid receptor obviously.The identical results could be seen in the C-terminal point mutant S363A of ?opioid receptor and S369A of ?opioid receptor.It is well known that opioid receptor requires interaction with other proteins for function,regulation and trafficking.Although proteins such as PPL,FilaminA,PLD2,PKCI,GASP and EBP50/NHERF have been identified to interact with C-terminals of opioid receptors,the role of interaction of these proteins with opioid receptor in the dependence,tolerance and addiction of opioids is dubious.Therefore,looking for the proteins specifically interacting with the C-terminals of opioid receptor may be important to understand the mechanism of opioids addiction.
3.Endothelins system and myocardial hypertrophy
Linglei KONG ; Lingdi YAN ; Zehui GONG
Chinese Pharmacological Bulletin 2003;0(09):-
Cardiac hypertrophy is a major adaptational mechanism in stresses such as pressure overload and neurohumoral stimulation.As powerful vasoconstrictor peptides in cardiovascular system,especially the vascular endothelium,smooth muscle cells and cardiocyte,ETs play important physiological roles in the regulation of normal cardiovascular function.Excessive generation of ETs in local cardiac muscle has been linked to myocardial hypertrophy.Endothelin-1(ET-1) in cardiac muscle exerts its actions in the development of myocardial hypertrophy through binding to specific receptors and interacting with other vasoactive substance of local tissues.ET-1 can induce the hypertrophy for cardiocytes and the proliferation for cardiac fibroblasts by ETA.ETB receptors are implicated both in initiating and maintaining myocardial hypertrophy.As a new target of drug,ET receptors have become the research focus,and great progress has been made on the development of the ET antagonists.
4.Expression of Cannabinoid receptor 2 in the CNS and pharmacology of its agonists
Suyan LI ; Lingdi YAN ; Zehui GONG
Chinese Pharmacological Bulletin 1987;0(01):-
Two types of cannabinoid receptors,named cannabinoid receptor 1(CB1) and cannabinoid receptor 2(CB2),have been cloned.CB2 receptors are expressed predominantly in the peripheral immune tissues,but accumulating evidence has revealed that CB2 receptors are also expressed in CNS.Previous studies showed that CB2 agonists can cure and suppress formation of inflammatory and neurophathic pain without central effects after chronic administration.Therefore,they will have good clinical applications in the treatment of pain and neurodegenerative diseases.In this paper,we will review the tissue distribution of CB2 in CNS and pharmacological characteristics of the CB2 agonists have been reviewed.
5.Current research progress in glutamate transporter subtype GLT-1 and its regulated drugs
Chengmin LI ; Hui YAN ; Zehui GONG
Chinese Pharmacological Bulletin 2003;0(10):-
The homeostasis of extracellular glutamate concentration is critically regulated by glutamate transporters(GTs).Malfunction or decreased expression of GTs has been implicated in the pathogenesis of various nervous system diseases.And among the GTs,glutamate transporter 1(GLT-1)plays a critical role as "glutamate pump".Recent research also finds some GLT-1 variants which alternate C-terminal splicings.Altered expression of proteins encoded by splice variants of GLT-1 has been noted in a number of disease states.Maintaining a physiological range of extracellular glutamate through regulating GTs expression or function may improve some pathological conditions.Many drugs are reported that can regulate GTs.For example,ceftriaxone,phencyclidine,citicoline,riluzole,AKT,thrombosin can up-regulate the expression or function of glutamate transporters;etomidate,clozapine,aspartic acid analogs,endothelin can down-regulate the expression or function of glutamate transporters.In this paper,the drugs which effect GTs will be summarized in order to provide a new insight into the drug design and clinical treatment of neurological diseases.
6.Clinical effects analyses of nedaplati or docetaxel combined with radiotherapy on patients with locally advanced uterine cervical cancer
Yan ZHANG ; Zehui SUN ; Zelin SUN
Clinical Medicine of China 2015;31(5):435-437
Objective To investigate the efficacy of nedaplati docetaxel combined with radiotherapy on patients with locally advanced cervical cancer.Methods The clinical data of 99 cases with pathologically diagnosed advanced cervical cancer from Jun.2013 to jul.2014 in the Matemal and Child Health Care Hospital of Tangshan were recorded.The patients were randomly divided into the control group (45 cases only with radiotherapy) and the observation group(54 cases with nedaplati and docetaxel beside radiotherapy).Results The effective rate in observation group was 90.74%,higher than control group (71.11%,x2 =6.358,P =0.017).There were significant incidence of bone marrow suppression renal dysfunction and gastrointestinal both in two groups,but can endure.There was no significant difference in term of side effect in two groups (P >0.05).Conclusion The therapy of nedaplati and docetaxel combined with radiotherapy has better effect for patients with advanced cervical cancer and without significantly increasing side effect.
7.Behavioral effects of early-life social isolation on adult rats
Shuling LI ; Hui YAN ; Zehui GONG
Military Medical Sciences 2014;(10):791-794,822
Objective To investigate rats reared in social isolation as a model of behavioral symptoms of neurodevelop-mental psychiatric disorders including schizophrenia.Methods Male rat pups were housed in individual cages from post-weaning to adulthood.Locomotor activity detection, Morris water maze test and social interaction test were performed. Results Compared with controls, the social isolation-reared rats got more body mass, showed locomotor hyperactivity and increased social interaction, but significant spatial learning changes were not observed in Morris water maze test.Conclu-sion Exposing rats to social isolation can profoundly affect behavior in adulthood, which can be used to build animal mod-els of neurodevelopmental psychiatric disorders including schizophrenia.
8.Establishment and application of a mouse model for drug-induced schizophrenia.
Hui YAN ; Shuling LI ; Ruibin SU ; Zehui GONG
Acta Pharmaceutica Sinica 2013;48(4):484-8
Schizophrenia, described as the worst disease affecting mankind, is a severe and disabling mental disorder. Schizophrenia is characterized by complicated symptoms and still lacks a diagnostic neuropathology, so developing schizophrenia animal models which have quantifiable measures tested in a similar fashion in both humans and animals will play a key role in new therapeutic approaches. According to the symptoms of cognitive impairment and emotional disorder, the N-methyl-d-aspartate (NMDA)-receptor antagonist MK-801 was applied to induce schizophrenia-like behavior in mice. Locomotor activity and prepulse inhibition (PPI) were selected as indices and the effect of clozapine was also investigated in this model. The results showed that compared with the normal group, MK-801-treated mice exhibited significantly increased locomotor activity and impaired PPI, and pre-exposure to clozapine could ameliorate the abnormality and make it back to normal level. These findings suggest that the model we established could be a useful tool for antipsychotic drug screening.
9.Effects of different kinds of opiate receptor on oxycodone-induced hyperlococomotor and analgesia in mice
Yanli LIU ; Lingdi YAN ; Chunfu WU ; Zehui GONG
Chinese Pharmacological Bulletin 2003;0(11):-
Aim To investage the effects of ?、?、?-receptor on hyperlocomotor and analgesia in mice.Methods Locomotor activity experiment and hot-plate pain experiment were measured.Results Oxycodone dose-dependently enhanced locomotor response in mice.Naloxone,a unselective opioid receptor antagonists and naltrindole(?-selective opioid receptor antagonist)could attenuate the increase of locomotor acitivity induced by oxycodone,but naloxonazine,a ?-receptor antagonist had no such effect.?-receptor antagonist nor-Binltorphimine increased hyperlocomotion induced by oxycodone.In antinociceptive experiment,naloxonazine and naltrindole could not attenuate the that of oxycodone,but nor-Binaltorphimine could attenuate the antinociceptive effects of oxycodone.Conclusion Oxycodone-hyperlocomotor is probably mediated by ? opioid receptor,and antinocieptive effects of oxycodone is probably mediated by ? opioid receptor.
10.Value of combined CA125, CT and MRI in diagnosing the ovarian thecoma
Yan ZHANG ; Xiaoyuan QI ; Lixia WANG ; Zehui SUN
Clinical Medicine of China 2015;31(8):759-762
Objective To discusses the value of combined CA125 and CT/MR/ in diagnosing the ovarian thecoma.Methods Forty cases of patients with ovarian thecoma were retrospectively analyzed.The results of CA125 and the appearance of CT and MRI were recorded,the value of CA125 changes and CT/MRI features was analysed in the diagnosis of ovarian thecoma.Results The value of CA125 elevated in 17 cases of ovarian thecoma,and showed statistical significance in the ratio((12/35 vs.5/5;x2=2.274,P=0.046) and the levels of the value of CA125 ((90.24 ± 18.56) U/ml vs.(243.35 ± 20.45) U/ml;t =7.780,P =0.002).Compared with 40 cases of control group,elevated CA125 level showed no obviously statistical significance (t =5.348,P=0.22).Forty patients in CT and MRI were all single lesion,30 cases were solid neoplasm,the rest were cystic-solidary lesions or priority of cystic component,75% lesions were more than 5 cm,9 cases of lesions contains calcification.In pre-enhanced CT and MR/scan the lesions showed iso-density or signal-intensity,mildly enhanced;Twenty-two patients with ascites and 11 cases with symptoms in the elevating of estrogen.Combined the results of CA125 and the apperaance of CT and MR/,the accuracy of the diagnosis in ovarian thecoma was 85%.Conclusion CT and MR/imaging combining with CA125 can improve the diagnosis accuracy of ovarian thecoma.which should be given priorities.