1.Changes of Plasma Orphanin in Patients with Postpartum Depression
Dian HU ; Hang GU ; Xinru HONG
Chinese Mental Health Journal 1988;0(06):-
Objective:To study the changes of plasma orphanin (OFQ) level in post-partum depression (PPD). Methods:The level of plasma OFQ of 24 patients with post-partum depression (PPD group) and 25 healthy lying-in women (control group) were measured by radioimmunoassay.Results:The level of plasma OFQ in PPD group was 27.39?6.04 ng/L , and that of control group was 10.37?3.65 ng/L,the difference was statistically significant(P
2.Change of orphanin content in hypothalamus and peripheral blood of fetal rats with ischemia and hypoxia
Hang GU ; Dian HU ; Xinru HONG ; Yong LIANG
Chinese Journal of Tissue Engineering Research 2006;10(46):216-217
BACKGROUND: Orphanin (OFQ) is associated with ischemia/hypoxia,which may play an important role in the production and development of fetal distress and neonatal asphyxia.OBJECTIVE: To observe the change of OFQ content in hypothalamus and peripheral blood of intrauterine ischemia/hypoxia fetal rats and analyze the role of OFQ in the perinatal ischemia/hypoxia.DESIGN: Randomized controlled animal trial.SETTING: Department of Obstetrics and Gynecology, Changhai Hospital of the Second Military Medical University of Chinese PLA.MATERIALS: The experiment was performed at the Department of Obstetrics and Gynecology, Changhai Hospital of the Secon d Military Medical University of Chinese PLA from May 2002 to September 2003. A total of 12 Wistar female rats, with the mean body mass of 260 g were selected and fed routinely [provided by the experiment animal center of this university, number of certificate scxk(Hu)2002/0006].METHODS: The 12 female rats were randomized into three groups: control group, ischemia/hypoxia for 10 minutes group, ischemia/hypoxia for 20 minutes group with 4 rats in each group. Female rats in each group were pregnant. On day 21 of pregnancy, female rats in each group were cut the belly open, and the uterine vessels were incarcerated for 10 minutes in the ischemia/hypoxia for 10 minutes group with 21 fetal rats and 20 minutes in the ischemia/hypoxia for 20 minutes group with 17 fetal rats, respectively. Fetal rats were directly obtained from control group with 19 ones. None of fetal rats died. All the fetal rats received Apgar score and decapitation. The blood of trunk was collected and the whole brain was obtained. OFQ content in hypothalamus and peripheral blood was measured with radioimmunoassay.MAIN OUTCOME MEASURES: OFQ content in hypothalamus and peripheral blood of fetal rats in each group.RESULTS: Totally 57 rats were involved in the result analysis. ①The levels ofOFQ in hypothalamus and peripheral blood were (71±14) pg/g and (31±7) ng/L in ischemia/hypoxia for 10 minutes group, (114±21) pg/g and (58±11) ng/L in ischemia/hypoxia for 20 minutes group, (48±9) pg/g and (19±4) ng/L in the control group. Compared with the control group, the levels of OFQ in hypothalamus and peripheralblood increased in the ischemia/hypoxia for 10 minutes group and ischemia/hypoxia for 20 minutes group (P< 0.05, P < 0.01), and it in ischemia/hypoxia for 10 minutes group was significantly higher than that in ischemia/hypoxia for 20 minutes group (P < 0.05). ②The score of Apgar was lower in the two groups than in the control group (P < 0.01 ), of which it was lower in the ischemia/hypoxia for 20minutes group than in the ischemia/hypoxia for 10 minutes group (P < 0.05).CONCLUSION: The perinatal ischemia and hypoxia can induce the increase of OFQ content in hypothalamus and peripheral blood.
3.Relationship between fetal distress and endogenous opioid peptides levels of the venous blood and the umbilical blood in pregnant women
Dian HU ; Hang GU ; Xinru HONG ; Ningxia SUN ; Chenghai WANG
Chinese Journal of Tissue Engineering Research 2005;9(19):203-205
BACKGROUND: Endogenous opioid peptide is an important medium and regulator that participate in many physical and pathologic processes of the body. Its relationship with fetal encephalopathy has attracted much attraction.OBJECTIVE: To evaluate the role of endogenous opioid peptides (EOP) in fetal distress.DESIGN: A case-control observatory study based on healthy pregnant women.SETTING: Wards of the Department of Obstetrics and Gynecology of Changzheng Hospital Affiliated to Second Military Medical University of Chinese PLA.PARTICIPANTS: Eighty-three healthy women who were hospitalised in Changzheng Hospital and Changhai Hospital affiliated to the Second Military Medical University of Chinese PLA and met the inclusion criteria. Among them, 40 were normal healthy pregnant women(the control group) and 43 were healthy pregnant women with fetal distress(the fetal distress group).METHODS: Radioimmunoassay was used to measure the levels of blood EOP(β-endorphin, dynorphin A1- 13 and leu-enkephalin) of the venous blood of the pregnant women in fetal distress group and the control group and the EOP level in the umbilical blood of the newborns. Also, blood gas analysis of the blood from the umbilical artery was conducted.MAIN OUTCOME MEASURES: The levels of EOP in the venous blood of two groups of pregnant women and the umbilical blood of newborns and the correlation of EOP level with fetal distress.RESULTS: The levels of the umbilical artery blood EOP(β-endorphin,dynorphin A1-13 and leu-enkephalin) in the fetal distress group[(453± 68 ) ng/L, (242 ± 33)ng/L, and(498 ± 68)ng/L respectively] were significantly higher than those in the control group[ (251 ± 39) ng/L, (103± 22 )ng / L and(322 ± 40 )ng / L respectively ( t = 2. 713,2. 762, P< 0.01; t = 2. 132, P < 0.05 ) ]. The umbilical artery blood gas analysis;pH was (7.0 ± 0. 1 ) , PO2 was ( 1.7 ± 0.6) kPa, PCO2 was (8.9 ± 0. 7) kPa.The levels of β-endorphin were negatively correlated with pH and PO2 of the umbilical artery blood(r= -0.418 and -0.437, P < 0.01), but they were positively correlated with PCO2( r = 0. 442, P < 0. 05) . The level of dynorphin A1-13 was negatively correlated with pH and PO2( r = -0. 337,-0.383, P < 0.05), but it was positively correlated with PCO2(r= 0. 346, P < 0. 05). There was no significant difference among the three kinds of blood EOP of the two groups( P > 0.05).CONCLUSION: EOP participates in the pathological progress of the fetal distress and was closely correlated with the occurrence and development of the fetal distress. This finding has a reference value for early rehabilitation and intervention after the fetal was born that can be tested quantitatively.
4.Correlation of plasm orphanin level and monoamine neurotransmitters in patients with postpartum depression
Dian HU ; Hang GU ; Xinru HONG ; Zhijun JIN ; Yong LIANG ; Ying XIONG
Chinese Journal of Tissue Engineering Research 2007;11(30):6103-6105
BACKGROUND: Orphanin, which was found in recent years, is an important bioactive polypeptide. Its extensive distribution in the central nervous system and peripheral tissue suggests a function of adjusting global behaviors.OBJECTIVE: To explore the correlation of plasm orphanin level and monoamine neurotransmitters in patients with postpartum depression by determining the levels of orphanin and monoamine neurotransmitters such as 5-hydroxytryptamine (5-HT) and dopamine(DA) in patients.DESIGN: Case-control experiment taking diagnosis as evidence.SETTING: Departments of Obstetrics and Gynecology, Changzheng Hospital and Changhai Hospital, Second Military Medical University of Chinese PLA.PARTICIPANTS: Twenty-five healthy women and seventeen women patients with postpartum depression after delivery who came in the Department of Obstetrics and Gynecology, Changzheng Hospital and Changhai Hospital, Second Military Medical University of Chinese PLA for further consultation during February 2002 to October 2004 were enrolled in this study, and served as control group and postpartum depression group, respectively. All the enrolled women, aged 21 to 43 years, with fair education levels, and voluntarily participated in this study. Women patients of 15 to 25 days after delivery suffered from the incipient postpartum depression with total scores of Edingburgh Postnatal Depression Scale (EPDS) above 13. Informed consents were obtained from all the subjects.METHODS: The levels of orphanin and monoamine neurotransmitters in venous blood from 25 healthy women and 17 women patients with postpartum depression were determined. ① Sample collecting: Blood was taken from women in the postpartum depression group 2 weeks after onset, while from control group 35 days after delivery. ② Assay method:The level of orphanin was determined with radioimmunoassay (RIA). The reagent kit was provided by phoenix company (USA) and the procedure was strictly performed according to the instructions on the reagent kit. The levels of 5-HT and DA were measured with high-performance liquid chromatography or electrochemical detection method.MAIN OUTCOME MEASURES: ① Changes in the levels of orphanin as well as 5-HT and DA in postpartum depression group and control group. ② Correlation of the total scores of EPDS and the levels of orphanin in postpartum depression group.RESULTS: Twenty-five healthy women and seventeen women patients with postpartum depression after delivery all participated in the result analysis. ① The level of orphanin in the postpartum depression group[(27.39±6.04) ng/L] was significantly higher than that in the control group [(10.37±3.65) ng/L](P < 0.01),the levels of 5-HT in the postpartum depression group [(0.93±0.21) μmol/L] was remarkably lower than that in the control group[(1.43±0.36) μmol/L](P <0.05) ,and the levels of DA in postpartum depression group[(2.15±0.41) μmol/L] was obviously lower than that in the control group [(3.64±0.72) μmol/L]( P < 0.01). ②The level of orphanin was negatively correlated with those of 5-HT and DA in postpartum depression group(r = -0.601 , -0.593,P < 0.05). ③ The total scores of EPDS were significantly positively correlated with the level of orphanin (r = 0.512, P < 0.05), and negatively correlated with the levels of 5-HT and DA (r = -0.571,-0.526, P< 0.05).CONCLUSION: The level of orphanin in patients with postpartum depression is increased and is negatively correlated with the levels of 5-HT and DA, but positively correlated with the total scores of EPDS.
5.Experimental study of endogenous opioid peptides participating in the fetal distress
Dian HU ; Hang GU ; Xinru HONG ; Yihong LI ; Chenghai WANG ; Liping CAO ; Ping LI
Chinese Journal of Tissue Engineering Research 2005;9(7):246-248
BACKGROUND: Endogenous opioid peptides are mainly mediated by μ receptor and produce inhibitory effect on breathing and heartbeat, and because of this, fetal distress happens and develops. Therefore, μ receptor mediation is the most important way that endogenous opioid peptides participate in the fetal distress and the pathological process of suffocation. Β-FNA (β-Funaltrexamine, μ-receptor antagonist) and ICI174864(δ-receptor antagonist) are helpful to reduce the happening of fetal distress.OBJECTIVE: To explore the roles of μ and δ receptors in the fetal distress based on the point of view that opioid peptides are involved.DESIGN: Completely randomized allocation and randomized and controlled trial using experimental animals as the subjects.MATERIALS: Twenty healthy white New Zealand purebred rabbits were randomly divided into 5 groups, and among them 16 rabbits were pregnant for 30 days and were put to death with the method of suffocation. The fetal rabbits were taken out immediately after cesarean section, with 6 - 8 fetal rabbits in each den. The fetal rabbits were classified into the following groups: untreated fetal distress group, (fetal distress group, 29 fetal rabbits), normal saline rabbits group(Normal saline group, 25 rabbits), rabbit distress β-FNA group(β-Funaltrexamine ) (FNA group, 28 rabbits), fetal rabbits ICI174864 treatment group(ICI174864 group, 31 rabbits).INTERVENTIONS: Pregnant rabbits in the saline group, FNA group , ICI group were intravenously given a bolus of normal saline or the opiate antagonist β-FNA or ICI174864 and were then asphyxiated. Another 4 rabbits that were pregnant for 30 days were put to death with the cut on the neck, and 28 fetal rabbits were taken out as the control group. After being delivered by cesarean section, all rabbit fetuses in the above five groups were assessed by Apgar scoring for respiration, heartbeat, skin color, muscle tension, and response to stimulation at 1, 5, 10, 15 and 30 minutes of age.MAIN OUTCOME MEASURES: Apgar scoring for respiration, heartbeat,skin color, muscle tension, and response to stimulation at 1, 5, 10, 15 and 30 minutes of age was made.RESULTS: The total Apgar score for respiration, heartbeat, skin color, muscle tension in the control group was the highest (8. 8 ± 1.1 ). And that of FNA group was 6. 8 ± 1.7, obviously higherthan that of the fetal distress group (2.1 ±1.0) and the saline-treated pups(2.5±1. 1) and(t=2.832 and 2. 795, P < 0.01 ). That of group ICI was 4.9 ± 0.7, markedly higher than that of the saline-treated pups and the fetal distress group( t = 2. 232 and 2. 195, P < 0.05) . There was no marked difference between the saline group and the distress group ( P > 0.05 ) and between the FNA group and the control group(P < 0.05) . The total Apgar scores of the ICI group,saline group, and distress group were significantly lower than that of the control group ( t = 2.913,2. 893, P < 0.01 and t = 2. 174, P < 0.05).CONCLUSION: Endogenous opioid peptides participates in the process of the happening and development of fetal rabbit distress that is mediated by opioid peptides receptor, the effect of μ receptor was much more than that of δ receptor. This study provides a basis for the evaluation of fetal distress and intervening at an earlier stage to enhance prognostic function.
6.Mechanism of Congrong Zonggan Capsules in Improving Neuroinflammation and Cognitive Impairment in 5×FAD Mice Based on NF-κB/NLRP3 Signaling Pathway
Yanru ZHOU ; Xinru GU ; Yuru LIU ; Shun ZHANG ; Yaozhong LYU ; Zhenzhong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):130-138
ObjectiveTo investigate the effects of Congrong Zonggan capsules (CRZG) on cognitive impairment in the Alzheimer's disease (AD) model of mice and its related mechanisms. MethodsSPF grade 4-week-old 5×FAD mice were divided into a model group, low-dose CRZG (0.819 g·kg-1) and high-dose CRZG (1.638 g·kg-1) groups, and Donepezilepezil hydrochloride group (2 mg·kg-1), with eight mice in each group. Eight C57 mice with the same background were set as the normal group. After one week of adaptive feeding, mice were orally administered continuously for six months. On the 5th month of drug administration, Y maze, new object recognition, and Morris water maze tests were conducted separately. After administration, mouse brain tissue was taken, and the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in brain tissue were detected by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence (IF) was used to detect the expression of small glial cell markers Iba1, astrocyte markers GFAP, and amyloid protein 1-42 (Aβ1-42) in the hippocampus of the brain tissue. The hematoxylin-eosin (HE) staining was used to detect pathological changes in the hippocampus of brain tissue. Western blot was used to detect the expression of nuclear factor-κB (NF-κB) p65, NOD-like receptor protein 3 (NLRP3), cleaved Caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), and other proteins in the brain tissue. ResultsCompared with those in the normal group, the mice in the model group had obvious cognitive impairment. The spontaneous alternation rate of the Y maze was decreased, and the discrimination index of novel object recognition was decreased significantly (P<0.01). The escape latency in the water maze was shortened significantly (P<0.01). The contents of IL-6 and TNF-α in brain tissue were increased. The fluorescence levels of Iba1 and Aβ1-42 in the hippocampus were significantly increased (P<0.01). There was a significant increase in neuronal lesions, neuronal atrophy, loose arrangement of tissue structure, and abnormal erythrocyte aggregation in the hippocampus. The protein expressions of p-NF-κB p65/NF-κB p65, cleaved Caspase-1, ASC, IL-6, and IL-1β were significantly increased (P<0.05, P<0.01). Compared with the model group, the spontaneous alternation rate and discrimination index of the high-dose CRZG group were increased significantly (P<0.01), and the escape latency was shortened significantly (P<0.05, P<0.01). The content of IL-6 decreased in the brain, and that of TNF-α dropped significantly (P<0.01). The expression of Iba1 protein and Aβ1-42 in the hippocampus decreased significantly (P<0.05, P<0.01). The hippocampal neurons were densely arranged, and the pyramidal nuclei were clear and centered. The abnormal aggregation of red blood cells was alleviated. The value of p-NF-κB/NF-κB proteins and the expression of ASC, cleaved Caspase-1, IL-6, and IL-1β were significantly decreased (P<0.05, P<0.01). ConclusionCRZG can effectively improve cognitive impairment in 5×FAD mice with Alzheimer's disease, and its mechanism may be related to the regulation of the NF-κB/NLRP3 pathway to reduce the abnormal activation of microglia and inhibit neuroinflammation.