1.Experimental study on the treatment of postmenopausal osteoporosis with low-frequency pulsed electromagnetic fields.
Zidong AN ; Liqiang WANG ; Yi WU ; Yongjie PANG ; Keming CHEN ; Yuhai GAO
Journal of Biomedical Engineering 2025;42(5):1054-1061
This study aims to investigate the therapeutic efficacy of 50 Hz-0.6 mT low-frequency pulsed electromagnetic field (PEMF) on postmenopausal osteoporosis in ovariectomized rats. Thirty 3-month-old female SD rats were selected and divided into a sham operation group (Sham), an ovariectomized model group (OVX), and a low-frequency pulsed electromagnetic field (PEMF) treatment group, with 10 rats in each group. After 8 weeks, the whole-body bone mineral density (BMD) of each group of rats was measured. The treatment group began to receive PEMF stimulation for 90 minutes daily, while the OVX group only received a simulated placement without electricity. After 6 weeks of intervention, all rats were sacrificed and tested for in vitro BMD, micro-CT, biomechanics, serum biochemical indicators, and bone tissue-related proteins. The results showed that the BMD of the OVX group was significantly lower than that of the Sham group 8 weeks after surgery, indicating successful modeling. After 6 weeks of treatment, compared with the OVX group, the PEMF group exhibited significantly increased BMD in the whole body, femur, and vertebral bodies. Micro-CT analysis results showed improved bone microstructure, significantly increased maximum load and bending strength of the femur, elevated levels of serum bone formation markers, and increased expression of osteogenic-related proteins. In conclusion, this study demonstrates that daily 90-minute exposure to 50 Hz-0.6 mT PEMF effectively enhances BMD, improves bone biomechanical properties, optimizes bone microstructure, stimulates bone formation, and inhibits bone resorption in ovariectomized rats, highlighting its therapeutic potential for postmenopausal osteoporosis.
Female
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Animals
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Rats, Sprague-Dawley
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Osteoporosis, Postmenopausal/therapy*
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Rats
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Bone Density
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Ovariectomy
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Magnetic Field Therapy/methods*
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Electromagnetic Fields
2.Curcumin Induces Cycle Arrest of Colon Cancer HCT116 Cells via JAK1/STAT1/p21 Pathway
Tianshuo LI ; Zuowu XI ; Wenjie DONG ; Denghui SHI ; Yunrong LIU ; Zidong LIN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):74-82
ObjectiveTo investigate the effect of curcumin on the cycle arrest of human colon cancer HCT116 cells and decipher the possible molecular mechanism. MethodThe methyl thiazolyl tetrazolium (MTT) method was employed to examine the effects of curcumin (0, 12.5, 25, 50, 75, 100 μmol·L-1) and 5-fluorouracil (5-FU, 600 μmol·L-1) on the proliferation of HCT116 cells at different time points (24, 48, 72 h). Flow cytometry was employed to examine the cycle of HCT116 cells treated with curcumin (0, 25, 50, 75 μmol·L-1) and 5-FU. Western blot was employed to determine the expression of proteins in the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 1 (STAT1) /cyclin-dependent kinase inhibitor 1A (p21) pathway in HCT116 cells. The binding of STAT1 to p21 promoter region was detected by chromatin immunoprecipitation (ChIP). Small interfering RNA (siRNA) was employed to measure the role of STAT1 in regulating the expression of p21 and that of JAK1 in regulating the activation of STAT1 by Western blot and cellular immunofluorescence, respectively. ResultCompared with the blank group, the HCT-116 cells treated with curcumin and 5-FU showed decreased viability (P<0.05), increased proportions of cells in the G0/G1 phase (P<0.05), decreased proportions of cells in the S phase and G2/M phase (P<0.05), down-regulated protein level of phosphorylated p21 (P<0.05), and up-regulated protein level of p21 (P<0.05). Compared with the curcumin group, the p21 siRNA+ curcumin group presented decreased proportion of cells in G0/G1 phase (P<0.05). Compared with the blank group, curcumin elevated the level of phosphorylated STAT1 (p-STAT1) (P<0.05). Compared with the curcumin group, the curcumin + STAT1 siRNA group showcased up-regulated protein level of p21 in HCT116 cells (P<0.05). The mechanism study showed that curcumin treatment enhanced the enrichment of STAT1 in the p21 promoter region (P<0.05) compared with the blank group. Compared with the blank group, curcumin up-regulated the level of phosphorylated JAK1 (p-JAK1) (P <0.05). Compared with the curcumin group, the curcumin + STAT1 siRNA group demonstrated up-regulated protein levels of p-STAT1 and p21 in HCT116 cells (P<0.05). ConclusionCurcumin may induce the cycle arrest of human colon cancer HCT116 cells by activating the JAK1/STAT1/p21 signaling pathway.
3.Comparison of clinical medicine proficiency tests of China and Japan and the enlightenment
Kan LIU ; Fei YU ; Zhenyu WANG ; Zidong LIU ; Tian TIAN ; Shuyuan ZHENG
Chinese Journal of Medical Education Research 2024;23(2):280-284
The Clinical Medicine Proficiency Test developed by the National Medical Examination Center of China in 2020 aims to assess whether clinical medical students possess the necessary medical humanities and basic medical theoretical knowledge and skills required for clinical internships. Since 2002, Japan has implemented the pre-clinical clerkship objective structured clinical examination and computer-based testing, which share similarities with China's proficiency test in terms of examination objectives, content, format, and score evaluation. Through comparing the examinations of China and Japan, this article concludes that it is necessary to learn from Japan's experience to expedite the process of promoting the Clinical Medicine Proficiency Test as an industry admission examination in China. We suggest that medical schools should keep tracking the development of the proficiency test and fully leverage its role in urging students to pay more attention to clinical internships. We also urge medical schools to establish a three-level examination system based on post competency criteria in line with the standards of the National Medical Licensing Examination to improve the quality of medical education.
4.Effects of acupuncture on serotonin, histamine, substance P, and tryptase levels at sensitized points in model rats with knee osteoarthritis
Jiayi Yang ; Zidong Wang ; Jing Jiang ; Huiling Tian ; Shun Wang ; Yizhi Liu ; Zumao Cao ; Changqing Joseph Yang ; Zhigang Li
Journal of Traditional Chinese Medical Sciences 2024;11(4):500-512
Objective:
To elucidate the differences in manual acupuncture effectiveness at sensitized points by investigating the mechanisms of local skin action at different sensitization points in rats with knee osteoarthritis (KOA).
Methods:
Forty Sprague–Dawley rats were equally divided into control, model (1 mg of monoiodoacetate into the right knee joint cavity), sham operation, manual acupuncture at right Tianjing acupoint (MAR-SJ 10), and left SJ 10 groups. Safranine-O and fast green staining were used to assess the modeling. The morphological and functional changes in mast cells (MCs) were assessed during acupoint sensitization using toluidine blue and immunofluorescence staining. The levels of serotonin, histamine, substance P (SP), and tryptase at skin acupoints and serum levels of IL-β, IL-6, and TNF-α were detected using ELISA.
Results:
After 14 days of treatment, the number of MCs and their degranulation rates were statistically higher in the model group than in the control group (both P < .001). After applying acupuncture, the levels of 5-HT, HA, and SP at skin acupoints were lower than those in the model group (all P < .05), and tryptase level was higher (both P < .05). Tryptase level was higher on the skin at the MAL-SJ 10 acupoint than that on the MAR-SJ 10 acupoint (P = .004). Compared with the model group, the serum levels of IL-1β, IL-6, and TNF-α in the MAR-SJ 10 and MAL-SJ 10 groups were lower (all P < .05).
Conclusion
Acupuncture at KOA-sensitized acupoints mitigates joint injury in KOA rats and may bidirectionally regulate local MCs of these acupoints. This finding not only enhances the reference value of sensitizing points in clinical diagnosis and treatment, but also contributes to the understanding of the biological mechanisms underlying acupuncture intervention at sensitizing points.
5.Comparison of Wild and Cultivated Codonopsis pilosula Based onTraditional Quality Evaluation
Xiaoyan LAN ; Chunfang TIAN ; Zhilai ZHAN ; Li ZHOU ; Xiang LI ; Zidong QIU ; Tiegui NAN ; Qili YUAN ; Xiaoliang LIN ; Congkui TIAN ; Meilan CHEN ; Liping KANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):156-164
ObjectiveTo conduct a systematic comparative study on wild and cultivated Codonopsis pilosula(CP) from three aspects, including characters, microscopy, and contents of primary and secondary metabolites. MethodWild and cultivated CP samples were collected, their characters were measured using vernier caliper, tape measure and balance, the paraffin sections were stained with safranin-fixed green dyeing, and their microstructure were observed under the optical microscope. The content of alcohol-soluble extracts in wild and cultivated CP was determined according to the method for determination of extract under CP in the 2020 edition of Chinese Pharmacopoeia, the starch content was determined by anthrone colorimetry, the content of total polysaccharides was determined by kit method, Fiber analyzer was used to determine the content of fiber components, and ultra performance liquid chromatography(UPLC) was used to determine the content of monosaccharides, disaccharides and some secondary metabolites. Multivariate statistical analysis methods such as principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to screen key differential components between wild and cultivated CP on the basis of variable importance in the projection(VIP) value>1 and P<0.05. ResultIn terms of morphological characteristics, the "lion's head-like" shape, longitudinal wrinkles, and circumferential wrinkles below the root cap of wild CP were more pronounced in wild CP compared to the cultivated ones. Regarding transverse sectional features, wild CP had more fissures on the outer side of the cortex and a larger duramen. Under microscopic examination, wild CP had more stone cells, a larger proportion of xylem, and the presence of cork cells arranged in rings in the xylem, while cultivated CP has a larger proportion of phloem, smaller vessel diameters, and a more loosely arranged vascular system. In terms of primary metabolites, the contents of 45% ethanol-soluble extract and total polysaccharides in cultivated CP were significantly higher than those in the wild ones(P<0.05), the contents of lignin, hemicellulose, cellulose, fructose and glucose in wild CP were significantly higher than those in the cultivated ones(P<0.05), while sucrose content in the cultivated CP was significantly higher than that in the wild ones(P<0.05). Concerning secondary metabolites, the contents of tryptophan and tangshenoside Ⅰ in cultivated CP were significantly higher than those in the wild ones(P<0.05), whereas the contents of lobetyolinin, lobetyol and atractylenolide Ⅲ in wild CP were significantly higher than those in the cultivated ones(P<0.05). ConclusionThere are significant differences between wild and cultivated CP in terms of morphological characteristics, microscopic features and chemical composition. Glucose, fructose, sucrose, tangshenoside Ⅰ, tryptophan and cellulose components are the key differential components between wild and cultivated CP. Wild CP contains more polyacetylenes and fructose, whereas cultivated CP has higher levels of tangshenoside Ⅰ and sucrose, with noticeably lower cellulose content. These distinctions may be related to their growth conditions, growth years and cultivation techniques. Based on the results of this study, it is recommended to increase polyacetylenes and the content ratio of fructose to sucrose as an indicators to characterize different production methods of CP, in order to guide the high-quality production of CP.
6.Comparison of Wild and Cultivated Paeoniae Radix Rubra Based on Traditional Quality Evaluation
Chunfang TIAN ; Qiannan HU ; Zhilai ZHAN ; Xiaoyan LAN ; Xiang LI ; Li ZHOU ; Tiegui NAN ; Zidong QIU ; Liping KANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):165-174
ObjectiveTo compare wild and cultivated Paeoniae Radix Rubra(PRR) in three aspects, including character, microscope, determination of primary and secondary metabolites. MethodSeventeen batches of wild and nine batches of cultivated PRR were collected,their character data were measured by vernier caliper and scales, and their paraffin sections were made by safranin-fixed green dyeing for the observation of microscopic features. The content of ethanol-soluble extracts and total tannin from wild and cultivated PRR was determined by the method of general principle 2201 and 2202 in the 2020 edition of Chinese Pharmacopoeia, the content of polysaccharides was determined by phenol-sulfuric acid method. Anthrone colorimetry was used to determine the content of starch, and Van Soest method of washing fiber was used to determine the content of fiber. The contents of fructose, glucose and sucrose in wild and cultivated PRR were determined by ultra-high performance liquid chromatography evaporative light scattering detection(UPLC-ELSD), and the secondary metabolites(gallic acid, methyl gallate, catechin, oxypaeoniflorin, albiflorin, paeoniflorin, ellagic acid, 1,3,4,6-tetragalloylglucose, galloylpaeoniflorin, 1,2,3,4,6-O-pentagalloylglucose, naringenin, benzoylpaeoniflorin and benzoylalbiflorin) were determined by UPLC. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to analyze the data of wild and cultivated PRR, the contribution of different factors to the difference was determined according to the variable importance in the projection(VIP) value>1 and P<0.05. ResultIn term of characters, wild PRR showed the traditional characteristic of Zaopi Fencha, its outer skin was loose and easy to fall off, its surface had longitudinal furrow and wrinkle, but the outer skin of cultivated PRR was not easy to fall off, and its surface was relatively smooth. The radial texture of xylem of wild PRR cross-section was more obvious, showing radial striations, vacuoles and more cracks, while the radial texture of xylem of cultivated PRR cross-section was not obvious, dense and some had cracks. Microscopically, the number of radial vessels arranged in the xylem of wild PRR was more than that of cultivated PRR, the number of calcium oxalate clusters in the phloem and xylem of wild PRR was more than that of cultivated PRR, while the number of starch grains was significantly higher in cultivated PRR. In terms of the content of primary chemical constituents, the contents of polysaccharides and starch of cultivated PRR were significantly higher than those of wild PRR(P<0.05), while the contents of cellulose, lignin, fructose and glucose of wild PRR were significantly higher than those of cultivated PRR(P<0.05). The results of determination of 13 secondary metabolites showed that the contents of paeoniflorin, methyl gallate, catechin and oxypaeoniflorin in wild PRR were significantly higher than those in cultivated PRR(P<0.05), while the contents of albiflorin, gallic acid, ellagic acid, naringenin, benzoylpaeoniflorin and benzoylalbiflorin were significantly lower than those of cultivated PRR(P<0.05). A total of 10 variables contributing to the differentiation between wild and cultivated PRR were screened, including albiflorin, cellulose, benzoylpaeoniflorin, oxypaeoniflorin, naringenin, ellagic acid, starch, lignin, paeoniflorin and total tannins. ConclusionThere are significant differences between wild and cultivated PRR in characters, microscopic characteristics, contents of primary and secondary metabolites. It is suggested that the content ratio of paeoniflorin and albiflorin, the contents of oxypaeoniflorin and cellulose can be used as indicators to characterize production methods of PRR so as to improve the quality standard of PRR. This study can provide reference for the improvement of quality standard of PRR and the guidance of high quality production of PRR.
7.The effective connection of default mode network changes in patients with type 2 diabetes mellitus
Liying ZHANG ; Zhizhong SUN ; Limin GE ; Zidong CAO ; Weiye LU ; Wenbin QIU ; Yuna CHEN ; Shijun QIU
Chinese Journal of Diabetes 2024;32(2):91-96
Objective To investigate the influence of type 2 diabetes mellitus(T2DM)on cognitive function and the effective connectivity with in the default mode network(DMN)in the brain.Methods A total of 93 hospitalized patients diagnosed with T2DM were enrolled in this study as T2DM group from The First Affiliated Hospital of Guangzhou University of Chinese Medicine during September 2021 to December 2022.Simultaneously,108 healthy individuals were recruited from the community as normal control(NC)group.The cognitive functions were evaluated in the two groups.A random dynamic causal modeling approach was employed to analyze the effective connectivity within DMN in both groups.Additionally,Pearson correlation analysis was performed to examine the association between differential connectivity,clinical indicators,and cognitive scores in both groups.Results In comparison to the NC group,T2DM individuals exhibited statistically significant reductions in scores in the auditory verbal learning test(AVLT)for immediate recall and the digit symbol substitution test(DSST)(P<0.05).Additionally,they displayed a notable decrease in effective connectivity from the left lateral parietal cortex(LLPC)to the posterior cingulate cortex(PCC),as well as from the LLPC to the right lateral parietal cortex(RLPC)within the DMN(P<0.05).Pearson correlation analysis unveiled a negative association between HbA1c levels and the strength of effective connectivity from LLPC to PCC.Conversely,a positive correlation was observed between AVLT(immediate)scores and the strength of effective connectivity from LLPC to PCC and LLPC to RLPC.Additionally,DSST scores displayed a positive correlation with the strength of effective connectivity from LLPC to PCC(P<0.05).Conclusion Patients with T2DM display compromised effective connectivity from LLPC to PCC and LLPC to RLPC within the DMN network,and this alteration may associated with cognitive impairment.
8.Mechanism of LINC01410 promoting proliferation and migration in esophageal squamous cell carcinoma
Fei CAO ; Wenhao YU ; Xiaonan TANG ; Zidong MA ; Tingmin CHANG ; Yabin GONG ; Mingjuan LIAO ; Xiaohong KANG
China Oncology 2024;34(8):753-762
Background and purpose:Long non-coding RNA(lncRNA)LINC01410,with a length of 647 bp,participates in a variety of tumor biological processes.However,the role and mechanism of LINC01410 involved in esophageal squamous cell carcinoma(ESCC)remain unclear.This study aimed to explore the potential mechanism of LINC01410 promoting ESCC proliferation and invasion,to provide a potential prognostic indicator and therapeutic target for individuals with ESCC.Methods:Gene Expression Profiling Interactive Analysis 2(GEPIA2)databases were used to analyze the expression of LINC01410 and overall survival in esophageal squamous cell carcinoma data set in the Cancer Genome Atlas(TCGA).Gene Set Enrichment Analysis(GSEA)was performed to identify the underlying signaling pathways involved in the biological effects of LINC01410 in ESCC.A total of 62 pairs of ESCC tissues and paracancerous tissues from ESCC patients who underwent radical surgery in the Department of Thoracic Surgery at the First Affiliated Hospital of Xinxiang Medical College and the First People's Hospital of Pingdingshan City from January 2020 to December 2021 were collected.This project has been approved by the Hospital Ethics Committee(First Affiliated Hospital of Xinxiang Medical College,No.2018036;First People's Hospital of Pingdingshan City,No.2019-018).The expression of LINC01410 in ESCC tissues was detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).We transfected EC109 cells with LV-NC or LV-over/LINC01410 and EC9706 cells with shRNA-NC or shRNA-LINC01410.Stable transfected cells(EC109/NC,EC109/OE,EC9706/NC and EC9706/KD)were selected in primary cell culture medium containing puromycin.The expression of LINC01410 was detected by RTFQ-PCR.The impact of LINC01410 on ESCC cell proliferation was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and colony formation assays.The effect of LINC01410 on ESCC cell invasion was detected by transwell migration assay.T cell factor/lymphoid enhancer factor 1(TCF/LEF1)luciferase reporter assay was performed to validate the effect of LINC01410 on the activity of canonical Wnt/β-catenin signaling pathway.The expressions of Wnt/β-catenin and epithelial-mesenchymal transition(EMT)signal pathway related proteins in ESCC cells were detected by Western blot.Results:By analyzing the LINC01410 expression from ESCC samples in TCGA by GEPIA2,we found LINC01410 was consistently increased in ESCC tumors compared with normal tissues(P<0.05),and high LINC01410 expression was associated with poorer overall survival(OS).RTFQ-PCR assay showed that expressions of LINC01410 were higher in esophageal cancer tissues and esophageal cancer cells(EC109 and EC9706)than in precancerous tissues and HEEC cells(P<0.05).The expression level of LINC01410 was significantly correlated with invasion range,lymph node metastasis and TNM stage in ESCC patients(P<0.01).LINC01410 expression was also upregulated in EC109/OE,however the expression of LINC01410 in EC9706/KD was decreased(P<0.01).MTT assay showed overexpression of LINC01410 increased the viability of EC109 cells,while knockdown of LINC01410 decreased the viability of EC9706 cells(P<0.01).Colony formation assay indicated that overexpression of LINC01410 enhanced the clonogenic ability of ESCC cells,while knockdown of LINC01410 reduced colony formation(P<0.01).Transwell migration assay showed that LINC01410 overexpression drastically increased the number of migratory cells,while silencing of LINC01410 suppressed the migration in EC9706 cells(P<0.01).GSEA revealed that Wnt/β-catenin and EMT pathways were significantly enriched in ESCC samples with a high level of LINC01410.TCF/LEF1 luciferase reporter assay showed higher levels of Wnt-dependent activities were observed in EC109/OE cells,whereas silenced LINC01410 in EC9706 cells led to contrary results(P<0.01).Western blot analysis showed that overexpression of LINC01410 in EC109 cell significantly increased the expression levels of N-cadherin,β-catenin,cyclin D1,c-Myc and decreased E-cadherin expression,while knockdown LINC01410 resulted in opposite results.Conclusion:LINC01410 promotes proliferation and metastasis of ESCC,which might be caused by activation of Wnt/β-catenin and EMT signaling pathways.
9.Research on a distance-adaptive visual function self-examination system based on a tablet computer
Mingqin WANG ; Zidong CHEN ; Yuning ZHANG ; Xiaoyuan SHEN ; Yanmei FAN ; Minbin YU
Space Medicine & Medical Engineering 2024;35(3):166-172
Objective Aiming to develop a distance-adaptive visual function self-examination system based on tablet computers and evaluate its accuracy.Methods Utilizing ArUco technology on a tablet device equipped with the camera,a system was developed to assess visual functions by identifying QR codes within a 2-meters range for real-time ranging.This system integrates various visual function tests,including visual acuity test(conventional visual acuity test and high-pass visual acuity test with varying contrasts),accommodative amplitude test,and visual field test at the foveal(5°).A total of 22 healthy subjects(44 eyes)participated in visual function assessments,with 6 subjects undergoing visual acuity tests at varying distances(1 m,1.25 m,1.6 m,2 m)and accommodative amplitude tests under both refractive correction and simulated undercorrection of-3.00D.The program distance and actual distance were compared,the consistency of visual acuity outcomes for identical optotype at different distances were assessed,the accommodative amplitude under refractive correction and undercorrection were analyzed,the repeatability of accommodative amplitude outcomes was evaluated using Intraclass Correlation Coefficient(ICC),and the contrast threshold and efficacy of visual field test outcomes were analyzed.Results The program distance and actual distance showed good agreement.High-pass visual acuity tests with the same contrast showed no significant differences at different distances(P?>?0.05),while conventional visual acuity tests showed significant differences at distances of 0.9 to 1.1 meters compared to other distances(P?0.001).ICC of accommodative amplitude tests was 0.861(P?0.001).The accommodative amplitude was lower in the undercorrected state compared to refractive correction,with a statistically significant difference(P?0.05).The average extreme outlier of contrast threshold for binocular visual field was 16.92,and the program correctly identified visual field defects.Conclusion Based on a tablet computer,this study developed a distance-adaptive visual function self-examination system capable of precisely measuring distances up to 2 meters in real-time.It automatically adjusts the initial size of optotypes according to the distance to ensure accurate presentation.The system facilitates tests on visual acuity,accommodative amplitude,and central 5° visual field,offering flexibility of tests in various distance and enhanced test power,making it suitable for visual function tests in constrained environments like space stations where fixed distances are impractica.
10.Research Progress on the Application of SAMP8 Mice in Anti-Dementia of Traditional Chinese Medicine
Guoqing WU ; Yushan GAO ; Zidong WANG ; Zhigang LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(4):886-894
The senescence accelerate mouse prone are a model of early learning and memory impairment,because they exhibit most of the characteristics of the pathogenesis of Alzheimer's disease,including abnormal expression of anti-aging factors,excessive increase of inflammatory factors,amyloid deposition,tau protein hyperphosphorylation,mitochondrial autophagy,the central mechanism of blood-brain barrier damage,and pathological damage of multiple systems and organs.Therefore,it has been widely used as an ideal model for Alzheimer's disease research.With the deepening of the experimental research on the mechanism of AD,it was found that SAMP8 mice showed obvious changes in behavior,histopathology and biochemical parameters compared with SAMR1,which were similar to human diseases.Therefore,this paper reviews the research progress of SAMP8 mice in recent years,in order to provide useful guidance and help for the application of SAMP8 mouse model in a variety of aging diseases.


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