Objective To observe the behavior changes and connexin 32(CX32),connexin 43(CX43)expressions in hippocampus and the effect of carbenoxolone on their expression in epileptic immature rats induced by lithium-pilocarpine.Methods Seventy-two SD immature rats of 21 d were randomly divided into control group(n=24),lithium-pilocarpine kindled group(n=24)and carbenoxolone treated group(n=24),each group by 24 h,3 d,7 d and 30 d were subdivided into 4 groups(n=6).Immuno-histochemisty was used to observe the expressions of CX32 and CX43 in hippocampus areas of immature rats,and to observe their behavior changes.Results The scores of the severe elileptiform seizures(Racine Ⅳ/Ⅴlevel)in lithium-pilocarpine group were significantly higher than those in carbenoxolone treated group;The latency in carbenoxolone treated group was prolonged significantly(P

Adult ; Aminosalicylic Acid ; therapeutic use ; Female ; Humans ; Manganese Poisoning ; drug therapy

OBJECTIVE: To study the pharmacokinetics of hot-melt spray-dried andrographolide granules and compare it with andrographolide bulk drug. METHODS: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for determination of the concentration of andrographolide in plasma of rats which were respectively given micronized andrographolide and hot-melt spray-dried andrographolide granules, then the pharmacokinetic parameters were calculated. RESULTS: The pharmacokinetic parameters of andrographolide after a single dose administration of micronized andrographolide and hot-melt andrographolide were as following: t1/2 were (347.33 ± 9.32) and (390.82 ± 8.78) min, tmax were (30.00 ± 5.94) and (60.00 ± 3.48) min, ρmax were (1 940.14 ± 21.21) and (1 818.22 ± 23.64) ng·mL-1, AUC0-t were (427 515.71 ± 37 350.03) and (426 406.31 ± 20 577.75) ng·min·mL-1, AUC0-inf were (545 423.14 ± 47 969.18) and (593 569.87 ± 30 247.35) ng·min·mL-1, Vz/F were (43.48 ±4.75) and (44.96 ± 3.81) kg · L-1, CL/F were (86.78 ± 3.35) and (79.74 ± 2.89) kg · L-1 · min-1, respectively. CONCLUSION: Compared with the bulk drug, the hot-melt spray-dried andrographolide granules have a longer t1/2, lower ρmax and delayed tmax in rats.

Objective To investigate the effects of electrical stimulation on vascular endothelial growth factor(VEGF) and its receptor expressions of neonatal rat brain with hypoxic-ischemic brain damage(HIBD).Methods Seventy-five 7-day-old newborn health SD rats were randomly divided into sham operation group(control group,n=25),hypoxia-ischemia group(model group,n=25) and the electrical sti-mulation group(intervention group,n=25).To bulid HIBD animal model of neonatal rats,the left common carotid artery was ligated and nitrogen-oxygen gas mixture was inhaled 2 hours.Fastigial nucleus stimulation was given 12 hours after the operation in intervention group,30 min?time-1,1 time?d-1,the time length was 1 d,3 d,7 d,14 d or 21 d,respectively.There was no electrical stimulation in model group and control group.The rats in these groups were captured at the corresponding time.Five rats in each group were killed at the corresponding pe-riods after electrical stimulation,the expression of VEGF and its receptor fam-like tyrosine kinase receptor(flt-1 / VEGFR1),fetal liver kinase receptor(flk-1/KDR/VEGFR2) in hippocampus were observed by immunohistochemistry.SPSS 15.0 software was used to analyze the data.Results The expression of VEGF,VEGFR1,VEGFR2 at every time point in electrical stimulation group were higher significantly than those in model group and control group(Pa0.05).Conclusion Electrical stimulation can promote the expression of VEGF and its receptors VEGFR1,VEGFR2.

Objective To explore the protective effect and the mechanism of fastigial nucleus electric stimulation on brain of rats with hypoxic-ischemic brain damage(HIBD).Methods Ninety rats were randomly divided into 3 groups:sham operated group(n=30),model group(n=30)and electric stimulation group(n=30),every group was divided into group A(n=10),group B(n=10)and group C(n=10)again.The models of perinatal HIBD rats were prepared by ligation of left common carotid artery with a temporary systemic hypoxia(N2O2 was 928)for 2 hours.Electric stimulation group was used electric stimulation for 20 minutes,2 times everyday after surgery.The sham operated group and model group was not used electric stimulation but catched to fix in corresponding period.All of the group A would be injected bromodeoxyuridine(BrdU)to enterocoelia before 8 hours when the rats would be killed and the group B would be not injected it.The rats of the group A and B would be killed and got the brain tissue after cardiac perfusion 7 days later,then,consecutively coronal slice.The changes of BrdU and nestin levels in brain were observed by immunohistochemistry staining assay.And the study and memory ability of all the group C would be tested by maze test after 28 days.The brain tissue would be tested by hematoxylin and eosin stain at the same time.All of the data would be described and analyzed by SPSS 13.0.More than a few means would be compared by One-Way analysis of variance and the t-test between 2 groups would be used.Results The BrdU and nestin levels of the model group were lower than the sham operated group(Pa

Objective To explore the influence of electrical stimulation on prefrontal cortical neurons and synaptic ultramicrostructure of hypoxic-ischemic brain damage(HIBD)in neonatal rats.Methods The sixty 7-day-old newborn healthy SD rats were randomly divided into hypoxic-ischemic group(model group),electrical stimulation(intervention)group and sham operation group(control group),which 20 for each group.The models of perinatal HIBD rats were prepared by ligation of left common carotid artery with a temporary systemic hypoxia for 2 hours.Intervention group was subject to electric stimulation for 30 minutes,once everyday after surgery.Control group and model group were not subject to electric stimulation but caught to fix in corresponding period.Fastigial nucleus electric stimulations were performed for 3 d,14 d and 21 d.Five rats were killed in each group after the application of electron microscope to observe the brain cortex neurons and synaptic ultrastructure changes.Results In model group,the neuronal shrinkage,the amount of organelles dacrease,ob-vious edema of cytoplasm,obvious swellen mitochondria,and synapse quantity decrease,synaptic space fusion,obvious synaptic vesicle were observed.Intervention group different times,mitochondria hydrops gradually alleviated,synaptic space gradually cleared,synaptic vesicle increased,pathological changes obviously lessened compared to model group at the same time,and there was no apparent abnormality compared with control group on the 21st d.Conclusion Electric stimulation can promote the ultramicrostructures recovery of HIBD rats.

Yinchenzhufu decoction (YCZFD) is a classic formula for treating Yin Huang syndrome, which can improve liver injury caused by cholestasis. However, the mechanism of action of YCZFD still remains unclear. This article used network pharmacology, molecular docking, animal experiments, and molecular biology methods to explore the mechanism of YCZFD in treating liver injury caused by cholestasis. A mouse model of acute cholestasis induced by lithocholic acid was used to investigate the effects of YCZFD on liver injury. The experimental procedures described in this paper were reviewed and approved by the Ethical Committee at the Shanghai University of Traditional Chinese Medicine (approval NO. PZSHUTCM190823002). The results showed that YCZFD could reduce the levels of blood biochemical indicators and improve hepatocyte damage of cholestatic mice. Then, multiple databases were used to predict the corresponding targets of YCZFD active components on cholestatic liver injury. An intersection target protein-protein interaction (PPI) networks based on String database and Cytoscape software was used to demonstrate the possible core targets of YCZFD against cholestatic liver injury. The results indicated that core targets of YCZFD include tumor necrosis factor, interleukin-1β, non-receptor tyrosine kinase Src, interleukin-6, etc. GO (gene ontology) and KEGG (kyoto encyclopedia of genes and genomes) enrichment analysis indicated that YCZFD may regulate the tumor necrosis factor signaling pathway, nuclear factor-κB signaling pathway, bile secretion, and other related factors to ameliorate the cholestatic liver injury. AutoDockTools software was used to perform molecular docking verification on the core targets and components of YCZFD. To verify the results of network pharmacology, UPLC-MS/MS method was used to determine the effect of YCZFD on levels of bile acid profiles in mouse liver tissues. It was found that treatment with YCZFD significantly reduced the content of free bile acids, taurine bound bile acids, and total bile acids in the liver tissues of cholestatic mice. Then, results from real time PCR and Western blot also found that YCZFD can upregulate the expression of hepatic nuclear receptor farnesoid X receptor, metabolizing enzyme (UDP glucuronidase transferase 1a1), and efflux transporters (bile salt export pump, multidrug resistance-associated protein 2, multidrug resistance-associated protein 3, etc) in cholestasis mice, promote bile acid metabolism and excretion, and improve bile acid homeostasis. Moreover, YCZFD can also inhibit pyroptosis and inflammation by regulating NOD-like receptors 3 pathway, thereby inhibiting cholestatic liver injury.

Bilirubin ; blood ; Child Development ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Neuropsychological Tests

Background Light-induced retinal damage models vary as many influence factors,herein the modeling method is difficult to copy.It is necessary to establish the grading standardization of retinal damage after retinal light exposure.Objective This study was to improve the modeling method and establish a grading standardization for light-induced retinal damage in rat.Methods Twenty-four SPF 8-10 week-old male SD rats were randomly divided into 4 groups and 6 eyes for each group.The rats were exposed to light intense of 5000 lx for 1,2,3 hours respectively in 3 groups,and other 6 rats served as the normal group.Full-field light exposure experiment was performed for each individual rat separately,and an annular illumination box was used tO ensure the experimental rat moving in a single direction and exposing the right eye in 5000 lx light surrounding during experimental duration.Ganzfeid electroretinogram(ERG)was recorded from the experimental rats at the fifth day after light exposure,and the animals were then sacrificed for histopathology observation to evaluate the retinal thickness change.All procedures which involved animals adhered to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.Results After exposing to intensity light for 1,2,3 hours,the b-wave amplitudes of rod response,maximal mixed response,oscillatory potential in scotopic ERG as well as cone response,20 Hz flicker response of photopic ERG were significant declined as lapse of light exposure time(F=71.690,P=0.000；F=56.250,P=0.000；F=23.610,P=0.000：F=27.130,P=0.000；F=27.030,P=0.000)and lowed by 26.2％,52.5％,70.7％,24.4％,39.3％,58.1％respectively at the end of experiment.Meanwhile,the b-wave latencies of rod response,maximal mixed response in scotopic ERG as well as cone response of photopic ERG were evidently different among different groups (F=1.370,P=0.282；F：0.800,P=0.508；F=11.840,P=0.000；F=2.080,P=0.136).Light induced retinal damage located mainly at the temporal retina area.After intensity light exposure for 1,2,3 hours,the thickness of outer nuclear layer at the superior temporal retina attenuated by 11.3％,25.6％and 72.5％,respectively(P<0.05).A significant difference was seen in mean thickness of outer nuclear layer at superior temporal retina among different groups(F=410.27,P=0.000). Conclusion A standardized grading method for light-induced retinal damage is recommended.The continuous illumination in a intensity of 5000 Ix for 1,2,3 hours can induce the mild,moderate or severe retinal damage respectively at temporal retina.

Objective The aim of this study was to investigate the characteristic of regional cerebral glucose metabolism in patients with Wilson's disease (WD) using 18F-fluorodeoxyglucose (FDG) PET.Methods Thirteen WD patients and 12 normal controls were studied by brain 18F-FDG PET, and the data were analyzed by visual analysis, semi-quantification and statistical parametric mapping (SPM). The radioactivity ratios of lenticular nuclei, caudate, thalamus and cerebellum to cerebral cortex and the ratio of lenticular nuclei to caudate were calculated, respectively. SPSS 11.0 software for statistics was also used to analyze the data. Results In WD patients, radioactivity of lenticular nuclei and candate was significantly decreased compared with controls. The radioactivity ratios of lenticular nuclei and caudate to cerebral cortex in WD patients were both significantly lower than that in normal controls (0.95±0.05 vs 1.26±0.05, t =15, P < 0.05 ; 1.02±0.06 vs 1.17±0.05, t = 8, P < 0.05), and the ratio of lenticular nuclei to caudate in WD patients was significantly higher than that in normal controls (0.93±0.06 vs 1.09±0.06, t =9, P< 0.05). Conclusion As compared with normal controls, patients with WD had significantly decreased glucose utilization in the basal ganglia, especially in the lenticullar nuclei.