Basic framework of science and technology system in the field of forensic medicine / 中国法医学杂志

Forensic medicine serves as a vital branch of medical science dedicated to aiding national and societal functions.Its longstanding application in practice and the role it plays in national governance make it evident that forensic medicine principally serves judicial and administrative bodies,earning it the moniker"State medicine".As a first-class discipline within the realm of medical sciences,forensic medicine is also a crucial part of evidential law,embodying both natural and social scientific characteristics.Over nearly a century of development,modern forensic medicine has evolved into an independent technological science discipline.Its comprehensive system encompasses forensic medicine knowledge system,academic system,disciplinary system,as well as technological system.The science and technology system of forensic medicine is inherently open,continuously interacting with other domains such as the knowledge of medicine,information science,mathematics,physics,and chemistry,which fosters a continuous influx of new insights and the adoption of interdisciplinary methods,effectively broadening the scope and depth of forensic science.Moreover,this system is characterized by its dynamism,propelled forward by the unyielding research and practical engagement of all the forensic experts.

Role of circTmeff-1 in morphine addiction memory of mice / 中国药理学与毒理学杂志

In addition to the essential pharmacologi-cal effects of opioids,situational cues associated with drug addiction memory are key triggers for drug seeking.CircRNAs,an emerging hotspot regulator in crown genet-ics-play an important role in central nervous system-relat-ed diseases.However,the internal mediating mechanism of circRNA in the field of drug reward and addiction mem-ory remains unknown.Here,we trained mice on a condi-tional place preference(CPP)model and collected nucle-us accumbens(NAc)tissues from day 1(T0)and day 8(T1)for high-throughput RNA sequencing.qRT-PCR revealed that circTmeff-1 was highly expressed in the NAc core but not in the NAc shell,suggesting that it plays a role in addiction memory formation.Meanwhile,the reverse regulation of circTmeff-1 by adeno-associated viruses could both inhibit the formation of addiction mem-ory in the NAc core or shell.Subsequently,the GO and KEGG analyses indicated 21 that circTmeff-1 might regu-late the addiction memory via the MAPK and AMPK path-ways.These findings suggest that circTmeff-1 in NAc plays a crucial role in morphine-dependent memory for-mation.

Antrodia cinnamomea exerts an anti-hepatoma effect by targeting PI3K/AKT-mediated cell cycle progression in vitro and in vivo

Antrodia cinnamomea is extensively used as a traditional medicine to prevention and treatment of liver cancer. However, its comprehensive chemical fingerprint is uncertain, and the mechanisms, especially the potential therapeutic target for anti-hepatocellular carcinoma (HCC) are still unclear. Using UPLC‒Q-TOF/MS, 139 chemical components were identified in A. cinnamomea dropping pills (ACDPs). Based on these chemical components, network pharmacology demonstrated that the targets of active components were significantly enriched in the pathways in cancer, which were closely related with cell proliferation regulation. Next, HCC data was downloaded from Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) and DisGeNET were analyzed by bioinformatics, and 79 biomarkers were obtained. Furtherly, nine targets of ACDP active components were revealed, and they were significantly enriched in PI3K/AKT and cell cycle signaling pathways. The affinity between these targets and their corresponding active ingredients was predicted by molecular docking. Finally, in vivo and in vitro experiments showed that ACDPs could reduce the activity of PI3K/AKT signaling pathway and downregulate the expression of cell cycle-related proteins, contributing to the decreased growth of liver cancer. Altogether, PI3K/AKT-cell cycle appears as the significant central node in anti-liver cancer of A. Cinnamomea.

Review and Prospect of Diagnosis of Drowning Deaths in Water / 法医学杂志

Drowning is the death caused by asphyxiation due to fluid blocking the airway. In the practice of forensic medicine, it is the key to determine whether the corpse was drowned or entered the water after death. At the same time, the drowning site inference and postmortem submersion interval (PMSI) play an important role in the investigating the identity of the deceased, narrowing the investigation scope, and solving the case. Based on diatoms testing, molecular biology, imaging and artificial intelligence and other technologies, domestic and foreign forensic scientists have done relative research in the identification of the cause of death, drowning site inference and PMSI, and achieved certain results in forensic medicine application. In order to provide a reference for future study of bodies in the water, this paper summarizes the above research contents.

Research Progress and Forensic Application of Postmortem Genetic Testing in Hereditary Cardiac Diseases / 法医学杂志

Hereditary cardiac disease accounts for a large proportion of sudden cardiac death (SCD) in young adults. Hereditary cardiac disease can be divided into hereditary structural heart disease and channelopathies. Hereditary structural heart disease mainly includes hereditary cardiomyopathy, which results in arhythmia, heart failure and SCD. The autopsy and histopathological examinations of SCD caused by channelopathies lack characteristic morphological manifestations. Therefore, how to determine the cause of death in the process of examination has become one of the urgent problems to be solved in forensic identification. Based on the review of recent domestic and foreign research results on channelopathies and hereditary cardiomyopathy, this paper systematically reviews the pathogenesis and molecular genetics of channelopathies and hereditary cardiomyopathy, and discusses the application of postmortem genetic testing in forensic identification, to provide reference for forensic pathology research and identification of SCD.

Effects of Chronic Restraint Stress on Apoptosis of Amygdala Cells in Rats / 法医学杂志

OBJECTIVES@#To explore the damage effects of chronic restraint stress (CRS) on amygdala cells through the rat CRS model.@*METHODS@#The rat CRS model was established, and the changes in body weight and adrenal mass in control group and CRS group were monitored at 1 d, 7 d, 14 d and 21 d. The behavior changes were evaluated by the percentage of retention time of open arms and open arm entries using the elevated plus maze (EPM). ELISA was used to detect the concentrations of rat's corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol. The changes of expression of glucocorticoid receptor (GR) and glial fibrillary acidic protein (GFAP) in amygdala were determined by immunohistochemistry and Western blotting. Ultrastructure changes of glial cell were observed by transmission electron microscopy. The apoptosis rate of amygdala was measured by flow cytometry.@*RESULTS@#Compared with the control group at the same time points, body weight of CRS 1 d, 7 d, 14 d and 21 d groups increased slowly, but adrenal mass increased significantly; the serum level of CRH, cortisol and ACTH increased significantly at 7 d, 14 d and 21 d respectively; the expression of GR in amygdala was increased while that of GFAP was decreased; EPM test suggested that the percentage of retention time of open arms and open arm entries decreased significantly after 14 d. The CRS group showed different degrees of glial cell damage in amygdala, and the apoptosis rate of glial cell was significantly increased in 21 d group.@*CONCLUSIONS@#This study successfully established a CRS model in rats, and anxiety-like behavioral changes in model rats may be caused by apoptosis of amygdala astrocytes.

The Role of Forensic Medicine in Responding to Emergencies and New Major Epidemics / 法医学杂志

In recent years, human beings are constantly facing the threat of emerging infectious diseases. Forensic technology plays a unique role in responding to the emergencies and new epidemics. In epidemic prevention and control, forensic partitioners can provide important clues for the identification of vector animal species and the traceability of pathogen regions based on non-human DNA testing technology. In epidemic-related judicial practice, forensic partitioners bear more and more evidence responsibilities in dealing with biosafety laws-related issues, such as improper handling of epidemics and vaccine safety issues, which require forensic evidence. In terms of pathogen tracing, forensic physical evidence examinations identify species and individuals through biological materials extracted from the scene of death and autopsy of infectious diseases, are expected to provide informative clues for epidemiological investigations and point out the direction for pathogen tracing. In addition, forensic pathological examination can provide an important pathophysiological basis for determining the cause of death and the mechanism of death through autopsy, also offer necessary scientific evidence for clarifying the epidemiological characteristics of the epidemic and predicting the development trend of the epidemic.

Epidemiological Characteristics of Sedative-Hypnotics and Opioid Painkillers at High-Frequency Exposure / 法医学杂志

Drug poisoning has a high incidence and serious consequences in medical institutions; its epidemiological characteristics also directly affect the changes in national laws and policies and the implementation of local management policies. Chinese statistics on drug-related abnormal death cases generally come from judicial appraisal centers and medical units. However, due to differences in work content and professional restrictions, there are differences in information management forms, which makes it difficult for appraisers to conduct a professional and systematic analysis of drug-related cases. This article focuses on the analysis of epidemiological characteristics of sedative-hypnotics and opioid painkillers and their exposure patterns in cases of poisoning death by analyzing the annual report of the American Association of Poison Control Center, combined with the characteristics of drug exposure in China.

Inhibitory Effect of CCK-8 on Methamphetamine-Induced Apoptosis / 法医学杂志

OBJECTIVES@#To investigate the inhibitory effect of cholecystokinin octapeptide (CCK-8) binding to cholecystokinin 2 receptor (CCK2R) on methamphetamine (METH)-induced neuronal apoptosis, and to explore the signal transduction mechanism of β-arrestin 2 in CCK-8 inhibiting METH-induced neuronal apoptosis.@*METHODS@#SH-SY5Y cell line was cultured, and HEK293-CCK1R and HEK293-CCK2R cell line were constructed by lentivirus transfection. Small interfering RNA (siRNA) was used to knockdown the expression of β-arrestin 2. Annexin Ⅴ-FITC/PI staining and flow cytometry were used to detect the apoptotic rate of cells, and Western blotting was used to detect the expression of apoptosis-related proteins.@*RESULTS@#The apoptosis of SH-SY5Y cells was induced by 1 mmol/L and 2 mmol/L METH treatment, the number of nuclear fragmentation and pyknotic cells was significantly increased, and the expression of apoptosis-related proteins Bax and cleaved caspase-3 were increased. CCK-8 pre-treatment at the dose of 0.1 mmol/L and 1 mmol/L significantly reversed METH-induced apoptosis in SH-SY5Y cells, and inhibited cell nuclear fragmentation, pyknosis and the changes of apoptosis-related proteins induced by METH. In lentivirus transfected HEK293-CCK1R and HEK293-CCK2R cells, the results revealed that CCK-8 had no significant effect on METH-induced changes of apoptosis-related proteins in HEK293-CCK1R cells, but it could inhibit the expression level of apoptosis-related proteins in HEK293-CCK2R cells induced by METH. The inhibitory effect of CCK-8 on METH-induced apoptosis was blocked by the knockdown of β-arrestin 2 expression in SH-SY5Y cells.@*CONCLUSIONS@#CCK-8 can bind to CCK2R and exert an inhibitory effect on METH-induced apoptosis by activating the β-arrestin 2 signal.

Research Progress on Forensic Genetics of Facial Morphological Depiction / 法医学杂志

Forensic DNA phenotyping （FDP） analysis uses DNA from biological samples left in crime scenes to predict individual phenotypic traits, such as geographical origin of ethnic group, height, weight, skin color, hair color and shape, iris color, male baldness, facial morphology, age, etc., thereby providing clues for case investigations. Among these traits, features of facial morphology are relatively more complicated. This paper makes an overall analysis of the measurement and collection of facial morphology, research on facial morphology related genes, forensic application and establishment of facial morphology depiction model, ethical issues, etc., then summarizes the latest research progress on features of facial morphology.

The Lymphatic Drainage Pattern of Internal Mammary Sentinel Lymph Node Identified by Small Particle Radiotracer ((99m)Tc-Dextran 40) in Breast / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to detect the lymphatic drainage pattern of internal mammary area and verify the concept of internal mammary sentinel lymph node (IM-SLN) in breast. MATERIALS AND METHODS: A small particle radiotracer ((99m)Tc-Dextran 40) was prepared and tested. (99m)Tc-Dextran 40 was injected into intraparenchyma at the sound breast by a modified radiotracer injection technique. Subsequently, dynamic single-photon emission computed tomography (SPECT), computed tomography (CT), and SPECT/CT combination images were performed to identify the radioactive lymph vessels and internal mammary lymph nodes (IMLNs). The direction of lymph drainage and the location of the IMLNs were identified in the SPECT/CT imaging. RESULTS: The radiochemical purity of (99m)Tc-Dextran 40 was > 95%. (99m)Tc-Dextran 40 could drainage into first, second, and third lymph node and the radioactive lymph node could be detected by the γ detector in the animal experiment. After (99m)Tc-Dextran 40 injecting into intraparenchyma, 50.0% cases (15/30) were identified the drainage lymphatic vessels and radioactive IMLNs by SPECT. The drainage lymphatic vessel was found from injection point to the first IMLN (IM-SLN) after 10.5±0.35 minutes radiotracer injection, and then (99m)Tc-Dextran 40 was accumulated into the IM-SLN. The combination imaging of SPECT/CT showed the second IMLN received the lymph drainage from the IM-SLN. The lymphatic drainage was step by step in the internal mammary area. CONCLUSION: The lymph was identified to drain from different regions of the breast to IM-SLN, and then outward from IM-SLN to other IMLN consecutively. It demonstrated the concept of the IM-SLN and provided more evidences for the application of internal mammary sentinel lymph node biopsy.

Effect of CCK-8 on expression of MMPs/TIMP-1 in TNF-α-induced RSC-364 / 中国药理学通报

Aim To observe the influence of CCK-8 on expression of MMPs/TIMP-1 in TNF-α-induced rat fibroblast-like synovial cell line RSC-364.Methods The secretion levels of MMP-1, MMP-3, MMP-9 and TIMP-1 were determined using ELISA;MMP-3 and MMP-9 mRNA expressions were detected by RT-PCR.Results MMP-3 and MMP-9 could not be examined in RSC-364 incubated with CCK-8 and unstimulated RSC-364, which was able to product a little MMP-1, TIMP-1 and express even less MMP-3,-9 mRNA.CCK-8 inhibited the increase in MMP-1, MMP-3, MMP-9 secretion and MMP-3,-9 mRNA expression in TNF-α-induced RSC-364.TIMP-1 production was also increased in TNF-α-induced RSC-364.CCK-8 had no effect on TIMP-1 production in TNF-α-induced RSC-364, but was able to reduce the ratios of MMP-1, MMP-3, MMP-9 to TIMP-1.Conclusion The inhibitory effect of CCK-8 on MMPs activity may be related to the decrease of MMPs mRNA expression, MMPs secretion and the ratios of MMPs to TIMP-1 in TNF-α-induced RSC-364, which indicates that CCK-8 might be a possible regulator in the pathogenesis of rheumatoid arthritis.

Study on the toxicokinetics of cymermethrin and its metabolites in dog bile / 中国法医学杂志

Objective To study the toxicokinetics of Cymermethrin and its metabolites in dog bile and provide evidence for forensic cases of identification of Cymermethrin poisoning. Methods 1/4LD50 doses of Cymermethrin were given to 6 male dogs by oral perfusion after the gallbladder fistula surgery on them,and their bile were collected at different time, in which Cymermethrin and its metabolites were extracted by Liquid-liquid extraction with dichloromethane and detected by HPLC-MS-MS. The qualitative analysis was based on retention time and MRM ions. The quantitative analysis was based on an internal standard method and calibration curve. Toxicokinetics equations of Cymermethrin and its metabolites in the bile were established from the c-t curves which were fitted by the WinNonlin toxicokinetics software meanwhie toxicokinetics parameters were obtained. Results The toxicokinetics of Cymermethrin met first-order dynamic equation. The Tmax of Cymermethrin(CYM), 3-phenoxybenzoic acid (3-PBA), 3-(2,2-Dichloroethenyl)-2,2-dimethyl-cyclopropanecarboxylate (DCVA) respectively were 1.52±0.30,1.29±0.04,0.93±0.41 h ; The Cmax of CYM, 3-PBA, DCVA respectively were 0.38±0.03,7.9±1.32,30.9±16.24 μg/mL ; The T1/2 of CYM, 3-PBA, DCVA respectively were3.93±0.71,1.36±0.11,4.49±2.81 h; Conclusion The toxicokinetics of Cymermethrin in dog bile met first-order dynamic equation ; The toxicokinetics model and parameters of Cymermethrin can provide evidence for forensic identification of Cymermethrin poisoning cases.

Mutation analysis of autosomal and X chromosomal STR in gynecologic and breast cancer / 中国法医学杂志

Objective To explore the mutation types and disciplines of STR commonly used in forensic in gynecologic and breast cancerand investigate the application of microdissection in forensic practice involving tumor tissue. Methods DNA of tumor tissues, adjacent normal tissues and peripheral blood from 62 patients with breast cancer, 62 patients with gynecologic cancer and 10 patients with benign gynecologic tumor were amplified by PowerPlex 21 System kit and Argus X-12 kit. Capillary electrophoresis of PCR products was carried out on an ABI 3130 Genetic Analyzer to obtain genotypes. Some tumor tissues with STR variation were microdissected. Results The genotype of peripheral blood in cancer patient was consistent with that of corresponding normal tissue. 4 types of STR variations were found in 46.77% gynecologic cancer tissues, compared with that in benign tumor tissues and breast cancer, the difference of STR variation was significant(P<0.01,P=0.009). The genotype of stromal cells separated by microdissection was consistent with that of corresponding adjacent normal tissue. Conclusion The STR loci detected in the study with poor stability are not suitable for forensic cases involving gynecologic cancer tissues. The genotype of stromal cells separated accurately from tumor tissues by microdissection could represent the normal DNA genotype of the individual with cancer. Microdissection is an effective solution in forensic cases with tumor tissues.

Glucocorticoid-induced rat primary amygdaloid neuron apoptosis / 中国药理学通报

Aim To investigate the role of GC in indu-cing apoptosis of amygdaloid neurons.Methods Cul-turing primary neurons of amygdala,the neurons were identified by immunefluorescence techniques with anti-body against microtubule associated protein-2 (MAP2 ) and antibody against GC receptor.Using flow cytome-try to detect the effects of different concentrations of dexamethasone on the amygdala neuron apoptosis. Then the experiment was divided into four groups:CON ,DEX ,DEX +MIF and MIF .The rate of apopto-sis of the four groups was detected by TUNEL tech-nique and the expressions of BAX mRNA of four groups by Real-time PCR technique.Results (1 )Compared with the control group, the percentage of apoptotic cells increased significantly with DEX(10 -8 mol·L-1~10 -6 mol · L-1 )treatment in a concentration-de-pendent manner.(2)the TUNEL test showed that the percentage of apoptotic cells of DEX group increased significantly,compared with control group.While it decreased significantly in DEX+MIF group,compared with DEX group.There was no difference between MIF group and control group.(3 )Compared with control group,the expressions of BAX mRNA of DEX group increased significantly.While the expressions of BAX mRNA of DEX +MIF group decreased significantly, compared with the DEX group.There was no difference between MIF group and control group.Conclusion GC can independently induce the apoptosis of primary cultured neurons in the amygdala by combining with GC receptor.

Cardiac Ultrastructure and Changes of HSP70 and HIF-1α Expression in Electric Shock Death Rats / 法医学杂志

Objective T o observe cardiac ultrastructure and the expression of heat shock protein 70 (H SP70) and hypoxia inducible factor-1α (H IF-1α) in electric shock death rats and to explore the application of these indexes as the basis of m edical identification in electric shock death. Methods Seventy-tw o SD rats w ere random ly divided into electric shock death group, postm ortem electric shock group and the control group. T he changes of m yocardial ultrastructure w ere observed by transm ission electron m icro-scope, and the expressions of m yocardial H SP70 and H IF-1α w ere observed by im m unohistochem ical technology. Results M yocardial m yofibril fracture, m itochondrial cristae and m em brane dissolution, and disordered arrangem ent of Z lines and M lines w ere observed in electric shock rats. H SP70 and H IF-1αw ere strong positive expressions in the electric shock death group, significantly com pared w ith the con-trol and postm ortem electric shock groups (P<0.05). Conclusion T he expressions of H SP70 and H IF-1αw ere obviously increased in electric shock death group, w hich m ay be used as the diagnostic indicator of electric shock death.

Cardiac Ultrastructure and Changes of HSP70 and HIF-1α Expression in Electric Shock Death Rats / 法医学杂志

OBJECTIVE@#To observe cardiac ultrastructure and the expression of heat shock protein 70 (HSP70) and hypoxia inducible factor-lα (HIF-lα) in electric shock death rats and to explore the application of these indexes as the basis of medical identification in electric shock death.@*METHODS@#Seventy-two SD rats were randomly divided into electric shock death group, postmortem electric shock group and the control group. The changes of myocardial ultrastructure were observed by transmission electron microscope, and the expressions of myocardial HSP70 and HIF-1α were observed by immunohistochemical technology.@*RESULTS@#Myocardial myofibril fracture, mitochondrial cristae and membrane dissolution, and disordered arrangement of Z lines and M lines were observed in electric shock rats. HSP70 and HIF-lα were strong positive expressions in the electric shock death group, significantly compared with the control and postmortem electric shock groups (P < 0.05).@*CONCLUSION@#The expressions of HSP70 and HIF-lα were obviously increased in electric shock death group, which may be used as the diagnostic indicator of electric shock death.

Study of genetic polymorphisms of 12 short tandem repeats on X chromosome in ethnic Han population from Hebei Province / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate genetic polymorphisms of 12 X chromosome short tandem repeat (X-STR) loci in ethnic Hebei Han population using an Investigator Argus X-12 amplification kit.</p><p><b>METHODS</b>DNA was extracted for 198 unrelated individuals (96 males and 102 females) and amplified with a fluorescence labeled multiplex PCR system. PCR products were separated and genotyped with capillary array electrophoresis.</p><p><b>RESULTS</b>Only DXS10103 and DXS10101 showed significant linkage disequilibrium at the 12 X-STR loci. One hundred and forty-eight alleles, including 22 off-ladder (OL) alleles, were observed at the 12 X-STR loci in the population. The heterozygosity and polymorphic information content (PIC) were 0.5074-0.9143 and 0.4377-0.9079, respectively. The power of discrimination (PD) was 0.5074-0.9143 in males and 0.6876-0.9863 in females. The mean exclusion chance was 0.4377-0.9079 in the trios cases and 0.2984-0.8373 in the duo cases, respectively.</p><p><b>CONCLUSION</b>The Investigator Argus X12 amplification system is highly polymorphic in ethnic Han population from Hebei and is useful for personal identification and paternity testing.</p>

Prostaglandin E2 receptors signaling on the differentiation of regulatory T cells and Th17 cells / 中华风湿病学杂志

Objective To study the receptors signaling of prostaglandin E2 on the differentiation of regulatory T (Treg) cells and Th17 cells.Methods The expression of prostaglandin E2 receptors (EP1/EP2/EP3/EP4) on the MACS-purified CD4+CD62L+ T (Th0) cells was analyzed by flow cytometry and reverse transcription polymerase chain reaction (RT-PCR).The quantity of CD25+Foxp3+ cells was examined by flow cytometry,the expression of FoxP3 mRNA and RORγt mRNA were detected using real-time RT-PCR,the level of IL-17 in the culture supernatants was detected by enzyme-linked immunosorbent assay (ELISA).ANOVA,LSD-t,Dunnett T3 were used for statistical analysis.Results EP1,EP2,EP3,EP4 were expressed on Th0 cells at different levels,and EP2 [(89.7±9.1)％] had the strongest expression.PGE2 [(3.0± 2.2) ％],EP2 agonist [(4.5± 1.0) ％] and EP4 agonist [(8.8 ±2.5) ％] decreased the quantity of CD25 +Foxp3 + cells compared with the control group [(28.6±6.8)％] (t=7.156,P=0.021; t=6.958,P=0.032; t=5.359,P=0.044).PGE2(0.210±0.020),EP1 agonist (0.833±0.045),EP2 agonist (0.227±0.025) and EP4 agonist (0.450±0.060) decreased the expression of Foxp3 mRNA compared with the control group (1.000) (t=23.817,t=5.026,t=23.313,t=16.581; all P=0.000).PGE2 [(22±6)pg/ml],EP2 agonist [(24±5)pg/ml]and EP4 agonist [(207±19) pg/ml] decreased the secretion of IL-17 compared with the control group [(678±87) pg/ml] (t=14.925,P=0.004; t=14.873,P=0.004; t=10.480,P=0.008).PGE2 (0.141±0.027),EP1 agonist (0.869±0.033),EP2 agonist (0.176±0.029) and EP4 agonist(0.371±0.042) decreased the expression of RORγt mRNA compared with the control group (1.000) (t=34.046,t=5.184,t=32.673,t=24.962,all P=0.000).Conclusion EP1,EP2,EP3,EP4 receptors are expressed on CD4+CD62L+ T (Th0) cells at different levels.Prostaglandin E2 inhibits the differentiation of Treg cells and Th17 cells via the EP2 and EP4 receptors signaling.

Effects of CCK-8 and its receptor antagonists on expression of CREB and pCREB in prefrontal cortex and hippocampus of morphine withdrawal rats / 中国病理生理杂志

AIM:To observe the effects of cholecystokinin octapeptide (CCK-8) and its receptor antagonists on cAMP response element binding protein ( CREB) and phosphorylated CREB ( pCREB) expression in frontal cortex and hippocampus of morphine withdrawal rats , which aim to explore the post-receptor mechanism through which CCK-8 regu-lates morphine withdrawal .METHODS: After the morphine dependence and naloxone-precipitated withdrawal animal models were established, the effects of CCK-8, L-364718 (CCK1 receptor antagonist) and LY-288513 (CCK2 receptor an-tagonist) pretreatment on CREB and pCREB expression in frontal cortex and hippocampus were observed by Western blot -ting and immunohistochemistry .RESULTS:In rat frontal cortex neuron , CREB was expressed in both cytoplasm and nu-cleus, but pCREB was only highly expressed in the nucleus .In the pyramidal cell layer of hippocampal CA 1 region, CREB showed high expression in the cytoplasm and low expression in the nucleus , while pCREB was only expressed in the nu-cleus.No obvious change of CREB was observed after either chronic morphine treatment or naloxone withdrawal .The pCREB expression was increased after chronic morphine treatment and further increased after naloxone withdrawal .Com-pared with the withdrawal group , chronic pretreatment with CCK-8, L-364718 and LY-288513 had no effect on CREB expression in the frontal cortex , but obviously decreased the pCREB expression .In the hippocampus , pretreatment with L-364718 and LY-288513 decreased CREB and pCREB expression , but only the pCREB expression was decreased after CCK-8 treatment.CONCLUSION:CCK-8 and CCK receptor antagonists may alleviate morphine withdrawal symptoms by regulating CREB , with specificity in different brain regions .