1.Hydrogen sulfide ameliorates hypoxic pulmonary hypertension in rats by inhibiting aerobic glycolysis-pyroptosis.
Yuan CHENG ; Yun-Na TIAN ; Man HUANG ; Jun-Peng XU ; Wen-Jie CAO ; Xu-Guang JIA ; Li-Yi YOU ; Wan-Tie WANG
Acta Physiologica Sinica 2025;77(3):465-471
The present study aimed to explore whether hydrogen sulfide (H2S) improved hypoxic pulmonary hypertension (HPH) in rats by inhibiting aerobic glycolysis-pyroptosis. Male Sprague-Dawley (SD) rats were randomly divided into normal group, normal+NaHS group, hypoxia group, and hypoxia+NaHS group, with 6 rats in each group. The control group rats were placed in a normoxic (21% O2) environment and received daily intraperitoneal injections of an equal volume of normal saline. The normal+NaHS group rats were placed in a normoxic environment and intraperitoneally injected with 14 μmol/kg NaHS daily. The hypoxia group rats were placed in a hypoxia chamber, and the oxygen controller inside the chamber maintained the oxygen concentration at 9% to 10% by controlling the N2 flow rate. An equal volume of normal saline was injected intraperitoneally every day. The hypoxia+NaHS group rats were also placed in an hypoxia chamber and intraperitoneally injected with 14 μmol/kg NaHS daily. After the completion of the four-week modeling, the mean pulmonary artery pressure (mPAP) of each group was measured using right heart catheterization technique, and the right ventricular hypertrophy index (RVHI) was weighed and calculated. HE staining was used to observe pathological changes in lung tissue, Masson staining was used to observe fibrosis of lung tissue, and Western blot was used to detect protein expression levels of hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate kinase isozyme type M2 (PKM2), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), GSDMD-N-terminal domain (GSDMD-N), Caspase-1, interleukin-1β (IL-1β) and IL-18 in lung tissue. ELISA was used to detect contents of IL-1β and IL-18 in lung tissue. The results showed that, compared with the normal control group, there were no significant changes in all indexes in the normal+NaHS group, while the hypoxia group exhibited significantly increased mPAP and RVHI, thickened pulmonary vascular wall, narrowed lumen, increased collagen fibers, up-regulated expression levels of aerobic glycolysis-related proteins (HK2 and PKM2), up-regulated expression levels of pyroptosis-related proteins (NLRP3, GSDMD-N, Caspase-1, IL-1β, and IL-18), and increased contents of IL-1β and IL-18. These changes of the above indexes in the hypoxia group were significantly reversed by NaHS. These results suggest that H2S can improve rat HPH by inhibiting aerobic glycolysis-pyroptosis.
Animals
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Rats, Sprague-Dawley
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Male
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Hypertension, Pulmonary/metabolism*
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Glycolysis/drug effects*
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Hydrogen Sulfide/therapeutic use*
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Hypoxia/complications*
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Rats
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Pyroptosis/drug effects*
2.Medication rules of Astragali Radix in ancient Chinese medical books based on "disease-medicine-dose" pattern.
Jia-Lei CAO ; Lü-Yuan LIANG ; Yi-Hang LIU ; Zi-Ming XU ; Xuan WANG ; Wen-Xi WEI ; He-Jia WAN ; Xing-Hang LYU ; Wei-Xiao LI ; Yu-Xin ZHANG ; Bing-Qi WEI ; Xian-Qing REN
China Journal of Chinese Materia Medica 2025;50(3):798-811
This study employed the "disease-medicine-dose" pattern to mine the medication rules of traditional Chinese medicine(TCM) prescriptions containing Astragali Radix in ancient Chinese medical books, aiming to provide a scientific basis for the clinical application of Astragali Radix and the development of new medicines. The TCM prescriptions containing Astragali Radix were retrieved from databases such as Chinese Medical Dictionary and imported into Excel 2020 to construct the prescription library. Statical analysis were performed for the prescriptions regarding the indications, syndromes, medicine use frequency, herb effects, nature and taste, meridian tropism, dosage forms, and dose. SPSS statistics 26.0 and IBM SPSS Modeler 18.0 were used for association rules analysis and cluster analysis. A total of 2 297 prescriptions containing Astragali Radix were collected, involving 233 indications, among which sore and ulcer, consumptive disease, sweating disorder, and apoplexy had high frequency(>25), and their syndromes were mainly Qi and blood deficiency, Qi and blood deficiency, Yin and Yang deficiency, and Qi deficiency and collateral obstruction, respectively. In the prescriptions, 98 medicines were used with the frequency >25 and they mainly included Qi-tonifying medicines and blood-tonifying medicines. Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Citri Reticulatae Pericarpium were frequently used. The medicines with high frequency mainly have warm or cold nature, and sweet, pungent, or bitter taste, with tropism to spleen, lung, heart, liver, and kidney meridians. In the treatment of sore and ulcer, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to promote granulation and heal up sores. In the treatment of consumptive disease, Astragali Radix was mainly used with the dose of 37.30 g and combined with Ginseng Radix et Rhizoma to tonify deficiency and replenish Qi. In the treatment of sweating disorder, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to consolidate exterior and stop sweating. In the treatment of apoplexy, Astragali Radix was mainly used with the dose of 7.46 g and combined with Glycyrrhizae Radix et Rhizoma to dispell wind and stop convulsions. Astragali Radix can be used in the treatment of multiple system diseases, with the effects of tonifying Qi and ascending Yang, consolidating exterior and stopping sweating, and expressing toxin and promoting granulation. According to the manifestations of different diseases, when combined with other medicines, Astragali Radix was endowed with the effects of promoting granulation and healing up sores, tonifying deficiency and Qi, consolidating exterior and stopping sweating, and dispelling wind and replenishing Qi. The findings provide a theoretical reference and a scientific basis for the clinical application of Astragali Radix and the development of new medicines.
Drugs, Chinese Herbal/history*
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Humans
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Medicine, Chinese Traditional/history*
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History, Ancient
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Astragalus Plant/chemistry*
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China
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Astragalus propinquus
3.Alleviation of hypoxia/reoxygenation injury in HL-1 cells by ginsenoside Rg_1 via regulating mitochondrial fusion based on Notch1 signaling pathway.
Hui-Yu ZHANG ; Xiao-Shan CUI ; Yuan-Yuan CHEN ; Gao-Jie XIN ; Ce CAO ; Zi-Xin LIU ; Shu-Juan XU ; Jia-Ming GAO ; Hao GUO ; Jian-Hua FU
China Journal of Chinese Materia Medica 2025;50(10):2711-2718
This paper explored the specific mechanism of ginsenoside Rg_1 in regulating mitochondrial fusion through the neurogenic gene Notch homologous protein 1(Notch1) pathway to alleviate hypoxia/reoxygenation(H/R) injury in HL-1 cells. The relative viability of HL-1 cells after six hours of hypoxia and two hours of reoxygenation was detected by cell counting kit-8(CCK-8). The lactate dehydrogenase(LDH) activity in the cell supernatant was detected by the lactate substrate method. The content of adenosine triphosphate(ATP) was detected by the luciferin method. Fluorescence probes were used to detect intracellular reactive oxygen species(Cyto-ROS) levels and mitochondrial membrane potential(ΔΨ_m). Mito-Tracker and Actin were co-imaged to detect the number of mitochondria in cells. Fluorescence quantitative polymerase chain reaction and Western blot were used to detect the mRNA and protein expression levels of Notch1, mitochondrial fusion protein 2(Mfn2), and mitochondrial fusion protein 1(Mfn1). The results showed that compared with that of the control group, the cell activity of the model group decreased, and the LDH released into the cell culture supernatant increased. The level of Cyto-ROS increased, and the content of ATP decreased. Compared with that of the model group, the cell activity of the ginsenoside Rg_1 group increased, and the LDH released into the cell culture supernatant decreased. The level of Cyto-ROS decreased, and the ATP content increased. Ginsenoside Rg_1 elevated ΔΨ_m and increased mitochondrial quantity in HL-1 cells with H/R injury and had good protection for mitochondria. After H/R injury, the mRNA and protein expression levels of Notch1 and Mfn1 decreased, while the mRNA and protein expression levels of Mfn2 increased. Ginsenoside Rg_1 increased the mRNA and protein levels of Notch1 and Mfn1, and decreased the mRNA and protein levels of Mfn2. Silencing Notch1 inhibited the action of ginsenoside Rg_1, decreased the mRNA and protein levels of Notch1 and Mfn1, and increased the mRNA and protein levels of Mfn2. In summary, ginsenoside Rg_1 regulated mitochondrial fusion through the Notch1 pathway to alleviate H/R injury in HL-1 cells.
Ginsenosides/pharmacology*
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Receptor, Notch1/genetics*
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Signal Transduction/drug effects*
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Mice
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Animals
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Mitochondrial Dynamics/drug effects*
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Mitochondria/metabolism*
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Cell Line
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Reactive Oxygen Species/metabolism*
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Oxygen/metabolism*
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Cell Hypoxia/drug effects*
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Cell Survival/drug effects*
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Membrane Potential, Mitochondrial/drug effects*
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Humans
4.Comparative Study of the Positive Psychological Resources Network of Adolescents With Non-Suicidal Self-Injury
Yuge JIA ; Xiao LIAO ; Yuan FENG ; Ting ZHU ; Xuan CAO ; Wei ZHANG
Journal of Sichuan University (Medical Sciences) 2025;56(3):864-872
Objective To explore the differences in positive psychological resources among elementary and secondary school students with and without non-suicidal self-injury(NSSI)behaviors.Methods Between September and October 2023,the assessment data of 56 870 students aged 9 to 18 years in Chengdu,Sichuan Province were collected.The R software package was used to evaluate the network structure and symptom centrality,and the global strength and structural differences of the networks of students with and without NSSI behaviors in elementary,junior high,and senior high schools were compared.Results The prevalence of NSSI among elementary and secondary school students stands at 12.21%.Specifically,it peaks in junior high school students,reaching 14.22%,followed by that in senior middle school students at 13.66%,and is lowest in elementary school students at 10.17%.Regarding the network structure in elementary school students,irrespective of the presence or absence of NSSI behavior,subjective support exhibits the strongest network strength,and family functioning demonstrates the highest closeness centrality.Among junior high school students without NSSI behaviors,the strongest network strength was observed in subjective support,whereas for those with NSSI behaviors,self-esteem showed the strongest network strength.In addition,subjective support exhibited the highest closeness centrality in both groups.In senior high school students,self-esteem was the factor with the strongest network strength for students with or without NSSI behaviors.For senior high school students without NSSI,subjective support had the highest closeness centrality,while for those with NSSI,expressive suppression showed the highest closeness centrality.The edge weights differed significantly among elementary school students in family functioning-self-esteem(E=0.093)and family functioning-objective support(E=0.087).For junior high school students,significant differences were found in objective support-subjective support(E=0.131)and family functioning-impulse control(E=0.109).Among senior high school students,significant differences were observed in impulse control-family function(E=0.133)and subjective support-utilization of support(E=0.130)(P<0.05).Conclusion Excessive family involvement in elementary school students and expressive suppression in senior high school students may be important influencing factors for NSSI behaviors.The lack of social support has a greater impact on junior and senior high school students.The strength of the connection among subjective support,objective support,and utilization of support is an important indicator.
5.PRELIMINARY INVESTIGATION OF EHRLICHIA AND NEOEHRLICHIA IN RODENTS AT THE IMPORTANT PORTS ALONG THE"BELT AND ROAD"
Xiao-Long ZHANG ; Jia XU ; Shi-Liang MA ; Pi-Zheng WANG ; Juan PAN ; Jia-Yuan CAO ; Zhi-Wen SUN ; Hui-Lin GUO ; Li-Li XIAO
Acta Parasitologica et Medica Entomologica Sinica 2025;32(3):160-166
Objective This study aimed to investigate natural infection of rodents with Ehrlichia and Neoehrlichia at major Chinese land-border ports along the"Belt and Road".Methods In 2022,rodents were monitored in 10 ports in northern and southern China and identified based on diagnostic morphological characteristics.The 16S rRNA genes of Ehrlichia and Neoehrlichia were detected by PCR using universal primers from rodent samples and phylogenetic analysis was performed based on the sequences of the detected positive pathogens.Results A total of 356 rodents were sampled,including 2 orders,5 families,15 genera,and 20 species.Predominantly,73,61,56,and 58 were Meriones unguiculatus(20.51%),Rattus norvegicus(17.13%),Apodemus agrarius(15.73%),and Microtus gregalis(16.29%).Only one Microtus fortis from Suifenghe Port was infected with Ehrlichia sp.Moreover,12 rodents were infected with Neoehrlichia spp.(overall positivity rate:3.37%).Conclusions Natural infections with Ehrlichia spp.and Neoehrlichia spp.were demonstrated in rodents at important Chinese land-border ports.The positivity rate of Neoehrlichia spp.was high in some ports,indicating that surveillance for ticks and their prevention and control measures should be intensified in these regions.
6.Discussion on the Scientific Connotation of Fortifying Spleen, Resolving Phlegm and Dispelling Stasis in the Treatment of Coronary Heart Disease under the Guidance of Dysfunctional High-Density Lipoprotein
Lianqun JIA ; Qige WANG ; Guoyuan SUI ; Nan SONG ; Huimin CAO ; Liang KONG ; Meijun LV ; Yuan CAO ; Ning YU ; Siyuan DING ; Guanlin YANG
Journal of Traditional Chinese Medicine 2024;65(2):128-133
The key pathogenesis of coronary heart disease (CHD) is spleen deficiency and phlegm stasis, and dysfunctional high-density lipoprotein (dys-HDL) may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein (HDL), it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL; and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways, namely, mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells, thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency, and spleen deficiency makes foundation for the production of dys-HDL; dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen, resolving phlegm, and dispelling stasis, is proposed as an important principle in the treatment of CHD by traditional Chinese medicine, which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL, thus revealing the scientific connotation of this method, and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.
7.Simultaneous GC-MS determination of sixteen pesticide residues and safety assessment for Lycii Fructus
Jia-Qi QIN ; Qiang-Qiang QI ; Ya-Jun ZHANG ; Yan WANG ; Si-Yuan ZHAO ; De-Yan CAO ; Mei-Lin ZHU
Chinese Traditional Patent Medicine 2024;46(1):143-149
AIM To establish a GC-MS method for the simultaneous content determination of sixteen pesticide residues in Lycii Fructus and perform safety assessment.METHODS The analysis was performed on DB-5MS chromatographic column(30 m×0.25 mm,0.25 μm)subjected to the programmed heating,with splitless injection of 1.0 μL dissolved sample at a flowing rate of 1.0 mL/min.Other parameters were as follows:injection port temperature of 250℃,electron impact ionization(EI),electron energy of 70 eV;ion source temperature of 230℃,multi-reaction monitoring mode,and collision gas.of high-purity N2.Pesticide residues with relatively high dietary risk were analyzed and discussed with regard to residue levels,dietary intake risk,risk ranking and cumulative exposure assessment.RESULTS Sixteen pesticides showed good linear relationships within their own ranges(r≥0.994 4),whose average recoveries were 70%-114%,with the RSDs of less than 2%.The highest average cyfluthrin residue of 0.999 2 mg/kg in Lycii Fructus of production regions and the highest average cypermethrin residue of 0.088 4 mg/kg in Lycii Fructus commodities were both detected.In Lycii Fructus of production regions with chronic hazard index(HI)value of 0.012 9 and acute HI value of 0.065 5 and their commodities with chronic HI of 0.001 2 and acute HI of 0.005 4,the pesticide residue of cypermethrin was the leading cause of chronic and acute dietary risk,and additionally,pyridaben within maximum residue limit(MRL)was the only detectectable highly toxic pesticide among the other most concerning pestcides of deltamethrin,pyridaben,chlorpyrifos,dichlorvos and methidathion.CONCLUSION There exist pesticide residues within MRL values in some samples of Lycii Fructus and the use of cypermethrin should be well-controlled.
8.Research on the clinical application effect of transcranial ultrasound patch probe
Bin ZHANG ; Changyang XING ; Wei HU ; Yang QU ; Jia WANG ; Xi ZHANG ; Yunyou DUAN ; Tiesheng CAO ; Lijun YUAN
Chinese Journal of Ultrasonography 2024;33(8):697-702
Objective:To evaluate the performance of the self-developed transcranial ultrasound patch probe as well as its stability and safety in clinical applications.Methods:This study was a cross-sectional study. Fifty healthy subjects in Tangdu Hospital from October to December 2023 were randomly and equally divided into two groups using a simple randomization method. The transcranial Doppler ultrasound (TCD) examinations were performed using the self-developed transcranial ultrasound patch probe and normal TCD probe alternatively in each group from squatting to sitting and then to standing posture. Two experienced sonographers (A, B) each completed one test for the same subject using the above two different probes. The differences of the ultrasound parameters of middle cerebral artery (MCA) blood flow measured by the self-developed transcranial ultrasound patch probe and the normal TCD probe in different postures (squatting, sitting, standing) were compared. At the same time, operator satisfaction with the use of the two probes was assessed in terms of time taken to obtain satisfactory images, operational comfort, and ease of handling. In addition, the subject's comfort during the examination was examined, and the signal acquisition stability of the two probes was comprehensively evaluated.Results:There was no significant difference in detection of various ultrasound parameters of MCA between using the transcranial patch probe and the normal TCD probe (all P>0.05). The overall satisfaction of transcranial ultrasound patch probe and normal TCD probe was quite similar. The transcranial ultrasound patch probe acquired favorable and stable signals. No subjects experienced adverse events/accidents during the examination of the subjects using the transcranial ultrasound patch probe as well as the normal TCD probe.Both probes had good and stable signal acquisition. Conclusions:TCD examinations could be well performed using the transcranial ultrasound patch probe, which might provide a potential new method for real-time monitoring and evaluating of cerebral blood flow of a moving subject.
9.Toxicity evaluation of alcohol extract of Polygonum multiflorum based on 3D hepatocyte ball model
Hua-Long SU ; Xiang-Cao YAO ; Jia-Min CHEN ; Bo-Hong CEN ; Ping WANG ; Zong-Zheng CHEN ; Zhong-Yuan XU
The Chinese Journal of Clinical Pharmacology 2024;40(9):1272-1276
Objective To explore the toxicity of Polygonum multiflorum alcohol extract on 3D hepatospheres.Methods Variations in culture conditions and cell ratios were implemented,followed by the assessment of cell sphere diameter,density,and roundness,aiming to explore the optimal culture conditions.The 3D hepatocyte spheres were divided into control group and experimental-L,-M,-H groups.The experimental-L,-M,-H groups were treated with 0.25,1.00 and 2.50 mg·mL-1 Polygounm multiforum alcohol extract,and the control group was given the same amount of culture medium.The cell viability of the cell spheroids was tested by CellTiter-Glo reagent,the expression level of liver function related genes was detected by fluorescent quantitative polymerase chain reaction(RT-qRCR).The toxicity of cell spheres was detected by double fluorescent staining of living and dead cells.Results The ideal culture condition of cell sphere was 500 cells per micropore,and the cell ratio was HepG2-Huvec-LX-2=8∶1∶1.It displayed the values of 0.91±0.07 for circularity,0.91±0.02 for firmness,1.12±0.14 for aspect ratio,and(170.97±14.79)μm for diameter.On the 3rd,7th,10th and 14th days,the expression levels of albumin(ALB)mRNA were 1.00±0.02,0.96±0.02,0.54±0.07,0.52±0.07,and the expression levels of cytochrome P450 1A2(CYP1A2)mRNA were 1.00±0.10,2.15±0.16,2.45±0.33,1.30±0.03,respectively.The expression levels of multidrug resistance protein 2(MPR2)in the control group and the experimental-L,-M,-H groups were 1.00±0.31,1.38±0.24,1.48±0.06 and 1.90±0.08,respectively;spheroid viability were(98.19±0.49)%,(88.53±0.90)%,(71.60±2.91)%and(56.65±5.41)%.There were statistically significant differences in the above indexes between the experimental-L,-M,-H groups and the control group(all P<0.05).Conclusion The established hepatocyte sphere co-culture model showed varying degrees of expression of phase Ⅰ/Ⅱ drug metabolism enzymes,transporters,and liver cell specific marker molecule albumin and can be used to evaluate the toxicity of multiflorum multiflorum,which provides further reference for the clinical application of multiflorum multiflorum.
10.Expression of brain-derived neurotrophic factor in hippocampal tissue of central obese mice induced by sodium glutamate
Peng-Juan CAO ; Jia-Yuan TANG ; Mei-Zi YANG ; Yuan-Yuan LI ; Li-Ting HUANG ; Wen-Wen MENG ; Yong-Jun JIN ; Jian-Xun MO
The Chinese Journal of Clinical Pharmacology 2024;40(15):2227-2230
Objective To explore whether the cognitive function of central obese mice is decreased by affecting the expression of brain-derived neurotrophic factor(BDNF)in hippocampus.Methods Healthy mice at the neonatal stage were divided into normal group and model group at random.To obtain the obese models,model group mice were injected at cervical subcutaneous with 10%L-monosodium glutamate(MSG;3 mg·g-1·d-1)for 5 days.The normal group was injected with the same dose of 0.9%NaCl.In addition,mice were removed according to the requirements.Finally,we got 8 mice in each group.The following parameters were compared:body weight,Lee's index and levels of the serum lipid.The BDNF expression levels in hippocampal tissue were measured using western blotting.Results At the 8th weekend,the body weight of the model and normal groups was(49.01±2.47)and(41.27±3.28)g;the Lee's indexes were(357.14±9.24)and(330.15±7.37)g1/3·cm-1;triglyceride levels were(1.37±0.52)and(0.73±0.31)mmol·L-1;total cholesterol levels were(2.98±0.18)and(1.98±0.30)mmol·L-1;low-density lipoprotein levels were(0.31±0.03)and(0.24±0.02)mmol·L-1;high-density lipoprotein levels were(2.70±0.15)and(1.98±0.40)mmol·L-1;the differences were statistically significant(P<0.05,P<0.01),which were consistent with the characteristics of the central obesity model.The BDNF protein expression levels in the hippocampus of the model and normal groups were 6.02 x 104±626.53 and 7.04 x 104±1 440.81,which has statistically significant(P<0.01).Conclusion The cognitive function of central obese mice may be decreased by down-regulating the expression of BDNF in hippocampus.

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