Production o f aromatics from lignin has attracted much attention. Because of the coexistence of C-O and C-C bonds and their complex combinations in the lignin macromolecular network, a plausible roadmap for de...Production o f aromatics from lignin has attracted much attention. Because of the coexistence of C-O and C-C bonds and their complex combinations in the lignin macromolecular network, a plausible roadmap for developing a lignin catalytic decomposition process could be developed by exploring the transformation mechanisms of various model compounds. Herein, decomposition of a lignin model compound, 2-phenoxyacetophenone (2-PAP), was investigated over several ce-sium-exchanged polyoxometalate (Cs-POM) catalysts. Decomposition of 2-PAP can follow two dif-ferent mechanisms: an active hydrogen transfer mechanism or an oxonium cation mechanism. The mechanism for most reactions depends on the competition between the acidity and redox proper-ties of the catalysts. The catalysts of POMs perform the following functions: promoting active hy-drogen liberated from ethanol and causing formation of and then temporarily stabilizing oxonium cations from 2-PAP. The use of Cs-PMo, which with strong redox ability, enhances hydrogen libera-tion and promotes liberated hydrogen transfer to the reaction intermediates. As a consequence, complete conversion of 2-PAP (〉99%) with excellent selectivities to the desired products (98.6% for phenol and 91.1% for acetophenone) can be achieved.展开更多
TGF-β is a multifunctional cytokine that regulates many aspects of cellular function, including periosteal mesenchymal cell proliferation, differentiation. This experiment is to study its effects on bone defect repai...TGF-β is a multifunctional cytokine that regulates many aspects of cellular function, including periosteal mesenchymal cell proliferation, differentiation. This experiment is to study its effects on bone defect repair. A rabbit radial bone defect model was used to evaluate the effect of TGF-β, which was extracted and purified from bovine blood platelets, on the healing of a large segmental osteoperiosteal defect. A 1. 5-centimeter segmental defect was created in the mid-upper part of the radial shaft of adult rabbits. The defect was filled with implant containing TGF-β that consisted of carrier and bovine TGF-β. Limbs served as controls received carrier alone. The defectswere examined radiographically and histologically at 4, 8,12 , 16 and 20 weeks after implantation. The results showed that in TGF-β implant group . the defect areas at 12 weeks post operation were bridged by uniform new bone and the cut ends of cortex could not be seen;while in control group, the defects remained clear. Only a small amount of new bone formed as a cap on the cut bone ends. In the experimental group, new lamellar and woven bone formed in continuity with the cut ends of the cortex. An early medullar canal appears to be forming and contained normal-appearancing marrow elements; while the control group displayed entirely fibrous tissue within the defect site. Remnants of the cancellous bone carrier were observed in the control specimen. These data demonstrate that exogenous TGF-β initiate osteogenesis and stimulate the bone defects repair in animal model.展开更多
The mechanism of ester hydrolysis has been extensively studied; however, the precise function of active-site residues in promoting catalysis is nuclear. We describe here the structural models for the complex of a cata...The mechanism of ester hydrolysis has been extensively studied; however, the precise function of active-site residues in promoting catalysis is nuclear. We describe here the structural models for the complex of a catalytic sntibody Fv fragment with a phosphonate transition -state analogue, constructed by using gene cloning, sequencing and molecular modeling, mainly based on a known X-ray structure of a catalytic atibody. Hydrophobic and electrostatic analyses of the Fv/analog and Fv/substrate interaction suggest the hydrolysis mechanism: In L91 and Tyr H97 play important roles to stabilize the β-naphthyl group of hapten through r-stack; His H35 donates a pair of free electrons at the atom NEZ to an active water and let it to be a partial hydroxide, which attacks the carbon atom of the carbonyl group of the substrate. Both His H35 and Arg L96 can form hydrogen bonds and stabilize the Anoinc tetrahedral intermediate formed during turnover. This mechanism emphasizes that an active water bridge may be formed during hydrolysis process.展开更多
With the continuous emergence and rapid spread of multidrug-resistant and extensively-drug-resistant Mycobacterium tuberculosis strains, it is imperative to develop novel therapies against this bacterium. The intrins...With the continuous emergence and rapid spread of multidrug-resistant and extensively-drug-resistant Mycobacterium tuberculosis strains, it is imperative to develop novel therapies against this bacterium. The intrinsic β-lactam resistance of M. tuberculosis is primarily due to the production of an Ambler class-A β-lactamase BlaC, which limits the application of β-lactam antibiotics in the treatment of tuberculosis. Therefore, the inhibitors of BlaC could be novel anti-tuberculosis drug synergistic agents to recover the sensibility of M. Tuberculosis to the β-lactam antibiotics. In the present study, BlaC of M. tuberculosis was expressed and purified to establish a screening model of the BlaC inhibitors. The screening conditions were determined, and the screening model was evaluated to fit for the high throughput screening. A total of 22 BlaC inhibitors were screened out from 26 400 compound samples with a positive rate of 0.083%. Taken together, our findings lay the foundation for the discovery of novel anti-tuberculosis drug synergistic agents in clinic.展开更多
OBJECTIVE: To explore the long-term effects and pain relief mechanism of acupotomy by observing changes in nitric oxide synthase (NOS) and beta-en- dorphin (~3-EP) in the hypothalamus, spinal cord, and peripheral...OBJECTIVE: To explore the long-term effects and pain relief mechanism of acupotomy by observing changes in nitric oxide synthase (NOS) and beta-en- dorphin (~3-EP) in the hypothalamus, spinal cord, and peripheral blood of rats with third lumbar ver- tebrae (L3) transverse process syndrome. METHODS: Twenty-eight SD rats were randomly as- signed to normal, model, electroacupuncture (EA), and acupotomy group. The last three groups were put through an operation to emulate L3 transverse process syndrome. Fourteen days after the simulation operation, EA and acupotomy treatments were applied to the respective groups. Fifty-six days afterthe simulation operation, biochemistry tests and enzyme-linked immunosorbent assay were used to measure NOS and 13-EP in the hypothalamus, spinal cord, and peripheral blood. RESULTS: Rats with the simulation operation showed significantly higher levels of NOS and II3-EP in the hypothalamus, spinal cord, and peripheral blood than those in the normal group. The EA and acupotomy groups had significantly lower levels of NOS and β-EP than those in the model group. There was no statistical difference between the EA and acupotomy groups. CONCLUSION: EA and acupotomy treatments significantly lowered NOS and β-EP levels in the hypothalamus, spinal cord, and peripheral blood and alleviated L3 transverse process syndrome.展开更多
β-decay properties of N=18-22,Z=10-14 nuclei are analyzed with a new shell-model Hamiltonian using the Gogny densitydependent interaction.The Gogny force which has been widely and successfully used in mean-field theo...β-decay properties of N=18-22,Z=10-14 nuclei are analyzed with a new shell-model Hamiltonian using the Gogny densitydependent interaction.The Gogny force which has been widely and successfully used in mean-field theory can provide reasonable two-body matrix elements for cross-shell calculations.The log f t values andβ-decay level schemes are systematically studied using the D1S-Gogny interaction and compared with the SDPF-M results and experimental data.It is shown that the new Hamiltonian provides reliable results forβ-decay along with subtle level schemes for this region.Shell-model calculations with Gogny interaction can lead to a successful description of nuclei in and around the N=20 island of inversion and supplements experiment where sufficient data are not available.展开更多
OBJECTIVE: To investigate the effect of Bushenyisui Formula on cell apoptosis and positive B cell lym- phoma (Bcl-2) in the Brain of rat models of Alzheim- er's disease (AD) induced by beta-amyloid protein (All...OBJECTIVE: To investigate the effect of Bushenyisui Formula on cell apoptosis and positive B cell lym- phoma (Bcl-2) in the Brain of rat models of Alzheim- er's disease (AD) induced by beta-amyloid protein (All3) and the mechanism underlying the effect. METHODS: Total of 40 SD rats, 20 females and 20 males, were randomly assigned to 4 groups, con- trolled group (A), model group (B), conventional treatment group (C) and Bushenyisui Formula treat- ment (BYFT) group (D), 10 rats in each group. AI3 1-42 was injected into the bilateral hippocampus of the rats in group B, C and D to create the models of AD. Sham operation was performed on the rats of group A in the same way by injecting equal volume of 0.9% sodium chloride solution into their bilateral hippocampus. 5 days after operation, Bushenyisui Formula was intraperitoneally administered at a dose of 450 mg/kg to the rats of group D (QD) for 20 days. Equal volume of 0.9% sodium chloride solution was intraperitoneally injected into the rats of group B with the same procedure. C suspension (20 mg/mL) was intraperitoneally injected into the rats of group B with the same procedure. The number of apoptot- ic cells in Brain and the positive Bcl-2 were count- ed. The changes of learning and memory abilities were evaluated using Y-maze. RESULTS: Right after the establishment of the mod- els, group B, C and D compared to group A respec- tively, the outcomes of Y-maze were significantly different from that of group A, which suggested ob- vious learning and memory disorder in those groups (P〈0.01). After treatment, the times of elec- tronic shocks of group C and D were significantly less than that of group B (P〈0.05), and the numbers of apoptotic cells and positive Bcl-2 were signifi- cantly different from those of group B, apoptotic sells' number of group C and D smaller than that of group B and the number of positive Bcl-2 greater than that of group B. CONCLUSION: Bushenyisui Formula could increase the number of Bcl-2 in brain, which improved the function of nervous system pertaining to learning and memory abilities.展开更多
OBJECTIVE:To observe the effects of Compound Danshen Tablets(CDST) on spatial cognition and expression of brain b-amyloid precursor protein(β-APP) in a rat model of Alzheimer's disease.METHODS:The rat model of Al...OBJECTIVE:To observe the effects of Compound Danshen Tablets(CDST) on spatial cognition and expression of brain b-amyloid precursor protein(β-APP) in a rat model of Alzheimer's disease.METHODS:The rat model of Alzheimer's disease(AD) was established using D-galactose to cause subacute aging combined with Meynert nucleus damage.Rat behavior was monitored using the Morris water maze,and the expression of β-APP in rat brain tissue was detected via immunohistochemistry.RESULTS:CDST significantly improved spatial cognition and decreased β-APP expression in the cortex and hippocampus(P<0.05,P<0.01).CONCLUSIONS:CDST can significantly improve spatial cognition in a rat model of AD.This observation is possibly related to a reduction in β-APP ex-pression in the rat brain.展开更多
OBJECTIVE: To study the effect of Qilongtoutong granule (QLTT) on plasma calcitonin gene-related peptide (CGRP), beta-endorphin (I[3-EP), 5-HT, dopa- mine (DA), noradrenalin (NE), and blood viscosity in mig...OBJECTIVE: To study the effect of Qilongtoutong granule (QLTT) on plasma calcitonin gene-related peptide (CGRP), beta-endorphin (I[3-EP), 5-HT, dopa- mine (DA), noradrenalin (NE), and blood viscosity in migraine model rats and mice. METHODS: Both the acute blood stasis model group and nitroglycerin-induced migraine model group included 60 Sprague-Dawley rats. The reser- pine-reduced model group had 60 Kunming mice. Rats from each test were grouped into normal con- trol group, model group, Zhengtian pill (ZTP) group, and high, moderate, or low-dose QLTT groups. In the acute blood stasis model test, after gavage for 7 days, rats were given 0.8 mL/kg adren- aline hydrochloride subcutaneously twice, and kept in ice water for 5 min. After fasting for 12 h, rats were anesthetized and blood samples were collected for detection of blood viscosity. In the nitro- glycerin-induced migraine group, after gavage for 7 days, rats were intraperitoneally injected nitro- glycerin (10 mg/kg), and 4 h later, blood samples were collected from postcava for measuring the plasma CGRP and 13-EP levels. In the reserpine-re- duced model test, except the normal control group, mice were administered reserpine (0.25 mg/ kg, i.h.) for 9 days. Mice received intragastric admin- istration from the third day to the ninth day. One hour after the last gavage, blood and brain tissue samples were obtained. Then, blood clotting time and the contents of neurotransmitters were deter- mined. RESULTS: QLTT- (3.6, 1.8, and 0.9 g/kg) and ZTP-treated rats had lower blood viscosity than that in model rats under different shear rates (P〈 0.01). QLTT- (3.6, 1.8 g/kg) and ZTP-treated rats had significantly lower plasma CGRP levels and higher plasma 13-EP levels than those in model rats (P〈 0.01). QLTT treatment at dose of 0.9 g/kg had lower plasma CGRP levels as well (P〈0.05). QLTT- (5.2, 2.6 g/kg) and ZTP-treated mice had longer blood clotting time than that in model mice (P〈0.01). QLTT- (2.6 g/kg) and ZTP-treated mice had higher plasma serotonin (5-HT) levels than those in model mice (P〈0.05). CONCLUSION: QLTT-treated animals had lower plasma CGRP level, higher plasma 13-EP, 5-HT, high- er brain tissue 5-HT, NE, DA levels, and lower blood viscosity than those in the migraine model animals.展开更多
Objective The double transgenic mouse model (APPswe/PSldE9) of Alzheimer's disease (AD) has been widely used in experimental studies. β-Amyloid (Aβ) peptide is excessively produced in AD mouse brain, which af...Objective The double transgenic mouse model (APPswe/PSldE9) of Alzheimer's disease (AD) has been widely used in experimental studies. β-Amyloid (Aβ) peptide is excessively produced in AD mouse brain, which affects synaptic function and the development of central nervous system. However, little has been reported on characterization of this model. The present study aimed to characterize this mouse AD model and its wild-type counterparts by biochemical and functional approaches. Methods Blood samples were collected from the transgenic and the wild-type mice, and radial arm water maze behavioral test was conducted at the ages of 6 and 12 months. The mice were sacrificed at 12-month age. One hemisphere of the brain was frozen-sectioned for immunohistochemistry and the other hemisphere was dissected into 7 regions. The levels ofAβ1-40, Aβ1-42 and 8-hydroxydeoxyguanosine (8-OHdG) in blood or/and brain samples were analyzed by ELISA. Secretase activities in brain regions were analyzed by in vitro assays. Results The pre-mature death rate of transgenic mice was approximately 35% before 6-month age, and high levels of Aβ1-40 and Aβ1-42 were detected in these dead mice brains with a ratio of 1 : 1 0. The level of blood-borne Aβ at 6-month age was similar with that at 12-month age. Besides, Aβ1-40 level in the blood was significantly higher than Aβ1-42 level at the ages of 6 and 12 months (ratio 2.37:1). In contrast, the level of Aβ1-42 in the brain (160.6 ng/mg protein) was higher than that of Aβ1-40 (74 ng/mg protein) (ratio 2.17:1). In addition, the levels of Aβ1-40 and Aβ1-42 varied markedly among different brain regions. Aβ1-42 level was significantly higher than Aβ1-40 level in cerebellum, frontal and posterior cortex, and hippocampus. Secretase activity assays did not reveal major differences among different brain regions or between wild-type and transgenic mice, suggesting that the transgene PS1 did not lead to higher 7-secretase activity but was more efficient in producing Aβ1-42 peptides. 8-OHdG, the biomarker of DNA oxidative damage, showed a trend of increase in the blood of transgenic mice, but with no significant difference, as compared with the wild-type mice. Behavioral tests showed that transgenic mice had significant memory deficits at 6-month age compared to wild-type controls, and the deficits were exacerbated at 12-month age with more errors. Conclusion These results suggest that this mouse model mimics the early-onset human AD and may represent full-blown disease at as early as 6-month age for experimental studies.展开更多
基金supported by the National Key Basic Research Program of China(973 program,2013CB934101)National Natural Science Foundation of China(21433002,21573046)+1 种基金China Postdoctoral Science Foundation(2016M601492)International Science and Technology Cooperation Projects of Guangxi(15104001-5)~~
文摘Production o f aromatics from lignin has attracted much attention. Because of the coexistence of C-O and C-C bonds and their complex combinations in the lignin macromolecular network, a plausible roadmap for developing a lignin catalytic decomposition process could be developed by exploring the transformation mechanisms of various model compounds. Herein, decomposition of a lignin model compound, 2-phenoxyacetophenone (2-PAP), was investigated over several ce-sium-exchanged polyoxometalate (Cs-POM) catalysts. Decomposition of 2-PAP can follow two dif-ferent mechanisms: an active hydrogen transfer mechanism or an oxonium cation mechanism. The mechanism for most reactions depends on the competition between the acidity and redox proper-ties of the catalysts. The catalysts of POMs perform the following functions: promoting active hy-drogen liberated from ethanol and causing formation of and then temporarily stabilizing oxonium cations from 2-PAP. The use of Cs-PMo, which with strong redox ability, enhances hydrogen libera-tion and promotes liberated hydrogen transfer to the reaction intermediates. As a consequence, complete conversion of 2-PAP (〉99%) with excellent selectivities to the desired products (98.6% for phenol and 91.1% for acetophenone) can be achieved.
文摘TGF-β is a multifunctional cytokine that regulates many aspects of cellular function, including periosteal mesenchymal cell proliferation, differentiation. This experiment is to study its effects on bone defect repair. A rabbit radial bone defect model was used to evaluate the effect of TGF-β, which was extracted and purified from bovine blood platelets, on the healing of a large segmental osteoperiosteal defect. A 1. 5-centimeter segmental defect was created in the mid-upper part of the radial shaft of adult rabbits. The defect was filled with implant containing TGF-β that consisted of carrier and bovine TGF-β. Limbs served as controls received carrier alone. The defectswere examined radiographically and histologically at 4, 8,12 , 16 and 20 weeks after implantation. The results showed that in TGF-β implant group . the defect areas at 12 weeks post operation were bridged by uniform new bone and the cut ends of cortex could not be seen;while in control group, the defects remained clear. Only a small amount of new bone formed as a cap on the cut bone ends. In the experimental group, new lamellar and woven bone formed in continuity with the cut ends of the cortex. An early medullar canal appears to be forming and contained normal-appearancing marrow elements; while the control group displayed entirely fibrous tissue within the defect site. Remnants of the cancellous bone carrier were observed in the control specimen. These data demonstrate that exogenous TGF-β initiate osteogenesis and stimulate the bone defects repair in animal model.
文摘The mechanism of ester hydrolysis has been extensively studied; however, the precise function of active-site residues in promoting catalysis is nuclear. We describe here the structural models for the complex of a catalytic sntibody Fv fragment with a phosphonate transition -state analogue, constructed by using gene cloning, sequencing and molecular modeling, mainly based on a known X-ray structure of a catalytic atibody. Hydrophobic and electrostatic analyses of the Fv/analog and Fv/substrate interaction suggest the hydrolysis mechanism: In L91 and Tyr H97 play important roles to stabilize the β-naphthyl group of hapten through r-stack; His H35 donates a pair of free electrons at the atom NEZ to an active water and let it to be a partial hydroxide, which attacks the carbon atom of the carbonyl group of the substrate. Both His H35 and Arg L96 can form hydrogen bonds and stabilize the Anoinc tetrahedral intermediate formed during turnover. This mechanism emphasizes that an active water bridge may be formed during hydrolysis process.
基金Fundamental Research Funds for Central Public Welfare Research Institutes(Grant No.2015PT350001)National Major Scientific and Technological Special Project for “Significant New Drugs Development”(Grant No.2015ZX09102007-009)
文摘With the continuous emergence and rapid spread of multidrug-resistant and extensively-drug-resistant Mycobacterium tuberculosis strains, it is imperative to develop novel therapies against this bacterium. The intrinsic β-lactam resistance of M. tuberculosis is primarily due to the production of an Ambler class-A β-lactamase BlaC, which limits the application of β-lactam antibiotics in the treatment of tuberculosis. Therefore, the inhibitors of BlaC could be novel anti-tuberculosis drug synergistic agents to recover the sensibility of M. Tuberculosis to the β-lactam antibiotics. In the present study, BlaC of M. tuberculosis was expressed and purified to establish a screening model of the BlaC inhibitors. The screening conditions were determined, and the screening model was evaluated to fit for the high throughput screening. A total of 22 BlaC inhibitors were screened out from 26 400 compound samples with a positive rate of 0.083%. Taken together, our findings lay the foundation for the discovery of novel anti-tuberculosis drug synergistic agents in clinic.
基金Supported by a Grant from the National Basic Research Program of China (973 Program)(No.2006CB504508)
文摘OBJECTIVE: To explore the long-term effects and pain relief mechanism of acupotomy by observing changes in nitric oxide synthase (NOS) and beta-en- dorphin (~3-EP) in the hypothalamus, spinal cord, and peripheral blood of rats with third lumbar ver- tebrae (L3) transverse process syndrome. METHODS: Twenty-eight SD rats were randomly as- signed to normal, model, electroacupuncture (EA), and acupotomy group. The last three groups were put through an operation to emulate L3 transverse process syndrome. Fourteen days after the simulation operation, EA and acupotomy treatments were applied to the respective groups. Fifty-six days afterthe simulation operation, biochemistry tests and enzyme-linked immunosorbent assay were used to measure NOS and 13-EP in the hypothalamus, spinal cord, and peripheral blood. RESULTS: Rats with the simulation operation showed significantly higher levels of NOS and II3-EP in the hypothalamus, spinal cord, and peripheral blood than those in the normal group. The EA and acupotomy groups had significantly lower levels of NOS and β-EP than those in the model group. There was no statistical difference between the EA and acupotomy groups. CONCLUSION: EA and acupotomy treatments significantly lowered NOS and β-EP levels in the hypothalamus, spinal cord, and peripheral blood and alleviated L3 transverse process syndrome.
基金supported by the National Key Basic Research Program of China(Grant No.2013CB834402)the National Natural Science Foundation of China(Grant Nos.11235001,11320101004,and 11575007)the China-U.S.Theory Institute for Physics with Exotic Nuclei(CUSTIPEN)funded by the U.S.Department of Energy,Office of Science(Grant No.DESC0009971)
文摘β-decay properties of N=18-22,Z=10-14 nuclei are analyzed with a new shell-model Hamiltonian using the Gogny densitydependent interaction.The Gogny force which has been widely and successfully used in mean-field theory can provide reasonable two-body matrix elements for cross-shell calculations.The log f t values andβ-decay level schemes are systematically studied using the D1S-Gogny interaction and compared with the SDPF-M results and experimental data.It is shown that the new Hamiltonian provides reliable results forβ-decay along with subtle level schemes for this region.Shell-model calculations with Gogny interaction can lead to a successful description of nuclei in and around the N=20 island of inversion and supplements experiment where sufficient data are not available.
文摘OBJECTIVE: To investigate the effect of Bushenyisui Formula on cell apoptosis and positive B cell lym- phoma (Bcl-2) in the Brain of rat models of Alzheim- er's disease (AD) induced by beta-amyloid protein (All3) and the mechanism underlying the effect. METHODS: Total of 40 SD rats, 20 females and 20 males, were randomly assigned to 4 groups, con- trolled group (A), model group (B), conventional treatment group (C) and Bushenyisui Formula treat- ment (BYFT) group (D), 10 rats in each group. AI3 1-42 was injected into the bilateral hippocampus of the rats in group B, C and D to create the models of AD. Sham operation was performed on the rats of group A in the same way by injecting equal volume of 0.9% sodium chloride solution into their bilateral hippocampus. 5 days after operation, Bushenyisui Formula was intraperitoneally administered at a dose of 450 mg/kg to the rats of group D (QD) for 20 days. Equal volume of 0.9% sodium chloride solution was intraperitoneally injected into the rats of group B with the same procedure. C suspension (20 mg/mL) was intraperitoneally injected into the rats of group B with the same procedure. The number of apoptot- ic cells in Brain and the positive Bcl-2 were count- ed. The changes of learning and memory abilities were evaluated using Y-maze. RESULTS: Right after the establishment of the mod- els, group B, C and D compared to group A respec- tively, the outcomes of Y-maze were significantly different from that of group A, which suggested ob- vious learning and memory disorder in those groups (P〈0.01). After treatment, the times of elec- tronic shocks of group C and D were significantly less than that of group B (P〈0.05), and the numbers of apoptotic cells and positive Bcl-2 were signifi- cantly different from those of group B, apoptotic sells' number of group C and D smaller than that of group B and the number of positive Bcl-2 greater than that of group B. CONCLUSION: Bushenyisui Formula could increase the number of Bcl-2 in brain, which improved the function of nervous system pertaining to learning and memory abilities.
基金Supported by the National Science and Technology "12th Five-years" Major Special-purpose Foundation (No 2011ZX09201-201-01)
文摘OBJECTIVE:To observe the effects of Compound Danshen Tablets(CDST) on spatial cognition and expression of brain b-amyloid precursor protein(β-APP) in a rat model of Alzheimer's disease.METHODS:The rat model of Alzheimer's disease(AD) was established using D-galactose to cause subacute aging combined with Meynert nucleus damage.Rat behavior was monitored using the Morris water maze,and the expression of β-APP in rat brain tissue was detected via immunohistochemistry.RESULTS:CDST significantly improved spatial cognition and decreased β-APP expression in the cortex and hippocampus(P<0.05,P<0.01).CONCLUSIONS:CDST can significantly improve spatial cognition in a rat model of AD.This observation is possibly related to a reduction in β-APP ex-pression in the rat brain.
基金Supported by National Science-technology Support Plan Projects (No.2013BAH14F03)
文摘OBJECTIVE: To study the effect of Qilongtoutong granule (QLTT) on plasma calcitonin gene-related peptide (CGRP), beta-endorphin (I[3-EP), 5-HT, dopa- mine (DA), noradrenalin (NE), and blood viscosity in migraine model rats and mice. METHODS: Both the acute blood stasis model group and nitroglycerin-induced migraine model group included 60 Sprague-Dawley rats. The reser- pine-reduced model group had 60 Kunming mice. Rats from each test were grouped into normal con- trol group, model group, Zhengtian pill (ZTP) group, and high, moderate, or low-dose QLTT groups. In the acute blood stasis model test, after gavage for 7 days, rats were given 0.8 mL/kg adren- aline hydrochloride subcutaneously twice, and kept in ice water for 5 min. After fasting for 12 h, rats were anesthetized and blood samples were collected for detection of blood viscosity. In the nitro- glycerin-induced migraine group, after gavage for 7 days, rats were intraperitoneally injected nitro- glycerin (10 mg/kg), and 4 h later, blood samples were collected from postcava for measuring the plasma CGRP and 13-EP levels. In the reserpine-re- duced model test, except the normal control group, mice were administered reserpine (0.25 mg/ kg, i.h.) for 9 days. Mice received intragastric admin- istration from the third day to the ninth day. One hour after the last gavage, blood and brain tissue samples were obtained. Then, blood clotting time and the contents of neurotransmitters were deter- mined. RESULTS: QLTT- (3.6, 1.8, and 0.9 g/kg) and ZTP-treated rats had lower blood viscosity than that in model rats under different shear rates (P〈 0.01). QLTT- (3.6, 1.8 g/kg) and ZTP-treated rats had significantly lower plasma CGRP levels and higher plasma 13-EP levels than those in model rats (P〈 0.01). QLTT treatment at dose of 0.9 g/kg had lower plasma CGRP levels as well (P〈0.05). QLTT- (5.2, 2.6 g/kg) and ZTP-treated mice had longer blood clotting time than that in model mice (P〈0.01). QLTT- (2.6 g/kg) and ZTP-treated mice had higher plasma serotonin (5-HT) levels than those in model mice (P〈0.05). CONCLUSION: QLTT-treated animals had lower plasma CGRP level, higher plasma 13-EP, 5-HT, high- er brain tissue 5-HT, NE, DA levels, and lower blood viscosity than those in the migraine model animals.
基金supported by ApoPharma Inc.through a collaborative research project between NRC-IBS and ApoPharma Inc
文摘Objective The double transgenic mouse model (APPswe/PSldE9) of Alzheimer's disease (AD) has been widely used in experimental studies. β-Amyloid (Aβ) peptide is excessively produced in AD mouse brain, which affects synaptic function and the development of central nervous system. However, little has been reported on characterization of this model. The present study aimed to characterize this mouse AD model and its wild-type counterparts by biochemical and functional approaches. Methods Blood samples were collected from the transgenic and the wild-type mice, and radial arm water maze behavioral test was conducted at the ages of 6 and 12 months. The mice were sacrificed at 12-month age. One hemisphere of the brain was frozen-sectioned for immunohistochemistry and the other hemisphere was dissected into 7 regions. The levels ofAβ1-40, Aβ1-42 and 8-hydroxydeoxyguanosine (8-OHdG) in blood or/and brain samples were analyzed by ELISA. Secretase activities in brain regions were analyzed by in vitro assays. Results The pre-mature death rate of transgenic mice was approximately 35% before 6-month age, and high levels of Aβ1-40 and Aβ1-42 were detected in these dead mice brains with a ratio of 1 : 1 0. The level of blood-borne Aβ at 6-month age was similar with that at 12-month age. Besides, Aβ1-40 level in the blood was significantly higher than Aβ1-42 level at the ages of 6 and 12 months (ratio 2.37:1). In contrast, the level of Aβ1-42 in the brain (160.6 ng/mg protein) was higher than that of Aβ1-40 (74 ng/mg protein) (ratio 2.17:1). In addition, the levels of Aβ1-40 and Aβ1-42 varied markedly among different brain regions. Aβ1-42 level was significantly higher than Aβ1-40 level in cerebellum, frontal and posterior cortex, and hippocampus. Secretase activity assays did not reveal major differences among different brain regions or between wild-type and transgenic mice, suggesting that the transgene PS1 did not lead to higher 7-secretase activity but was more efficient in producing Aβ1-42 peptides. 8-OHdG, the biomarker of DNA oxidative damage, showed a trend of increase in the blood of transgenic mice, but with no significant difference, as compared with the wild-type mice. Behavioral tests showed that transgenic mice had significant memory deficits at 6-month age compared to wild-type controls, and the deficits were exacerbated at 12-month age with more errors. Conclusion These results suggest that this mouse model mimics the early-onset human AD and may represent full-blown disease at as early as 6-month age for experimental studies.