Research progress in etiology of acute gallstone pancreatitis / 中华肝胆外科杂志

Acute gallstone pancreatitis (AGP) is a kind of acute pancreatitis caused by gallstones. The etiology of AGP is complex, and the anatomic basis and initiating factors have a synergistic effect on its pathogenesis, which needs to be studied jointly. The way of the confluence of pancreaticobiliary ducts, dilated main pancreatic duct, the relatively narrow opening of duodenal papilla and small stones or microlithiasis may be involved in the pathogenesis of AGP, in which small stones are the most important. Etiological diagnosis and clinical treatment of AGP should be carried out simultaneously. The timely selection of treatment methods for different causes can alleviate the patient's condition to the greatest extent and reduce the cost of treatment. At present, it is difficult to unify the prediction indexes of AGP. Meanwhile, the pathogenesis and related prophylaxis and treatment also need to be studied. In this paper, the anatomic basis, initiation factors, pathogenesis and self-defense of AGP were analyzed to provide a new perspective for its treatment.

The coronary heart disease of phlegm-stasis cementation syndrome in mini-swine based on platelet proteomics / 药学学报

Based on the technology of platelet proteomics, the key regulatory proteins and pathogenesis of coronary heart disease with phlegm and blood stasis syndrome were explored and analyzed. Based on the previous laboratory research, the model of coronary heart disease in mini-swine with phlegm-stasis cementation syndrome was duplicated. The model was judged by the changes in blood lipid and myocardial tissue characteristics. Furthermore, the platelet proteins were studied by quantitative proteomics, and the differentially expressed proteins were screened. The critical regulatory proteins and biological pathways of coronary heart disease with phlegm-stasis cementation syndrome were analyzed by bioinformatics. After ten weeks of modeling, the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL-C), triglyceride (TG), creatine kinase (CK) and creatine kinase-MB (CK-MB) in the model group were significantly increased, reflecting the pathological changes such as increased blood lipid, abnormal coagulation function and myocardial ischemia in the model group. In addition, compared with the sham group, there were 26 up-regulated proteins and 8 down-regulated proteins in the platelets of the model group. Combined with bioinformatics analysis, it was found that differential proteins mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction. Among them, lactate dehydrogenase B (LDHB), alcohol dehydrogenase 5 (ADH5), neuroblastoma ratsarcoma viral oncogene homolog (NRAS) and Kirsten ratsarcoma viral oncogene homolog (KRAS) play a central role when interacting with other proteins and simultaneously participate in multiple action pathways. The results showed that LDHB, ADH5, NRAS, and KRAS may be the marker proteins in CHD with phlegm-stasis cementation syndrome by regulating glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction and other biological processes.

Effect of asiaticoside on OGD/R induced injury of H9C2 cardiomyocytes based on PI3K/Akt/Beclin-1 signaling pathway / 药学学报

In order to investigate the effects of asiaticoside (Ass) on H9C2 cardiomyocytes, the present study examined the potential intervention of Ass on the proliferation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/Bcl-2 homology domain protein (Beclin-1) signaling pathway in H9C2 cardiomyocytes following oxygen and glucose deprivation/reperfusion (OGD/R) injury. H9C2 cardiomyocytes were selected as the research objects, and the activity of H9C2 was detected by cell counting kit-8 (CCK-8). H9C2 cells were divided into control group, OGD/R group, Ass low concentration group (10 μmol·L-1), Ass high concentration group (80 μmol·L-1) and Ass high concentration + chloroquine group (80 μmol·L-1 + 50 μmol·L-1). The control group was cultured under normal conditions, and the other groups were treated with oxygen and glucose deprivation for 4 h and reperfusion for 2 h. The activity and content of aspartic aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) in the supernatant of H9C2 cardiomyocytes were detected by enzyme-linked immunosorbent assay. Autophagy staining assay kit with monodansylcadaverine (MDC) method to observe cellular autophagy; molecular docking technique to identify the molecular targets of Ass. Immunofluorescence was used to observe the effect of the drug on cell number. The expression levels of PI3K, Akt, selective autophagy adaptor protein (P62) and Beclin-1 were detected by Western blot. Compared with OGD/R group, Ass group had a protective effect from 10-80 μmol·L-1, and the activities and contents of AST, LDH and CK were decreased. The protein expression levels of PI3K, Akt, P62 and Beclin-1 were decreased. Compared with the administration group, the activities and contents of AST, LDH and CK in Ass high-concentration + chloroquine group were significantly decreased, and the protein expression levels of PI3K, Akt, Beclin-1 and P62 were significantly decreased. Immunofluorescence showed that the inhibitor group and each administration group had different degrees of protective effect compared with the model group. Asiaticoside can reduce the injury of H9C2 cardiomyocyte induced by OGD/R, reduce the content of AST, LDH and CK, reduce the expression level of P62 protein, and reduce autophagy, which may be closely related to the inhibition of PI3K/Akt/Beclin-1 signaling pathway activation.

Proteomics reveals the protective mechanism of salvianolate injection on early hyperacute myocardial infarction / 药学学报

The hyperacute stage of myocardial infarction refers to a period of time within 30 minutes after the occurrence of myocardial infarction, when the symptoms are not obvious and the diagnosis is difficult, and the related pathophysiological mechanism has received less attention. In this study, proteomics was used to investigate the pathological changes in the early hyperacute phase of myocardial infarction, aiming to provide experimental evidence for pathological mechanism of myocardial infarction hyperacute stage. Meanwhile, the intervention effect and related mechanism of salvianolate injection were discussed based on heat shock protein B6 (HSPB6), aiming to benefit the clinical rational use of salvianolate injection. The protein expression changes before and after myocardial infarction model establishment were detected by label-free proteomics via mass spectrometry and analyzed by bioinformatics method. Then the binding effect of salvianolate injection on the commonly differential protein HSPB6 was evaluated by molecular docking technology, which was finally verified by animal experiments. All animal experimental protocols were approved by the Ethics Committee of Xiyuan Hosptial (2022XLC041). The results of this study showed that a total of 2 166 proteins were quantified by lable-free proteomics, of which 194 shared differential proteins were involved in myocardial injury and body regulation in the hyperacute phase of myocardial infarction, mainly involving molecular functions such as protein homodimerization activity, oxygen binding and transport, and serine endopeptidase inhibitor activity. Among them, HSPB6 protein is involved in the regulation of myocardial function. Molecular docking results indicated that magnesium salvianolate acetate, which is the main component of salvianolate injection, had the lowest binding energy with HSPB6 protein: -14.53 kcal·mol-1. Animal experiments showed that compared with the Sham group, the model group had significantly lower ejection fraction (EF) and fractional shortening (FS) (P < 0.001), cardiac blood perfusion decreased significantly (P < 0.001). There were obvious pathological changes such as myocardial fiber disorder, cardiomyocyte edema and interstitial small blood vessel congestion; the injury of cardiac function of rats in the administration group was attenuated, and the FS of rats in the low-dose group was significantly improved (P < 0.05), the pathological injury of myocardial tissue was markedly mitigated, and the expression of HSPB6 protein was up-regulated to varying degrees (P < 0.01, P < 0.001). In conclusion, salvianolate injection could be able to improve the cardiac function and pathological morphology of rats in the early hyperacute stage of myocardial infarction, and its mechanism may be related to the promotion of expression of HSPB6.

Interpretation of the World Society of the Emergency Surgery/the Global Alliance for Infection in Surgery/the Surgical Infection Society-Europe/the World Surgical Infection Society/the American Association for the Surgery of Trauma global clinical pathways for patients with intra- abdominal infections / 中华危重病急救医学

Intra-abdominal infections (IAI) is common surgical emergencies and have been reported as major contributors to non-trauma deaths in hospitals worldwide. The principles of IAI management included early diagnosis, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization using critical care resources, combined with an optimal surgical approach. In order to facilitate clinical management, establish a global standard and provide guidance for clinicians, the World Society of Emergency Surgery (WSES), the Global Alliance for Infection in Surgery (GAIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), and the American Association for the Surgery of Trauma (AAST) worked together to complete an international multi-society document, which provided the evidence-based clinical pathways. Herein, we made a comprehensive interpretation for the clinical pathways combined with the latest domestic and international research developments, aiming to provide evidence for domestic doctors on the diagnosis and treatment of IAI, and ultimately benefit patients.

Huoxin Pill Reduces Myocardial Ischemia Reperfusion Injury in Rats via TLR4/NFκB/NLRP3 Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To explore the protective effect of Huoxin Pill (HXP) on acute myocardial ischemia-reperfusion (MIRI) injury in rats.@*METHODS@#Seventy-five adult SD rats were divided into the sham-operated group, model group, positive drug group (diltiazem hydrochloride, DH), high dose group (24 mg/kg, HXP-H) and low dose group (12 mg/kg, HXP-L) of Huoxin Pill (n=15 for every group) according to the complete randomization method. After 1 week of intragastric administration, the left anterior descending coronary artery of the rat's heart was ligated for 45 min and reperfused for 3 h. Serum was separated and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), hypersensitive C-reactive protein (hs-CRP) and interleukin-1β (IL-1β) were measured. Myocardial ischemia rate, myocardial infarction rate and myocardial no-reflow rate were determined by staining with Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC). Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN) databases were used to screen for possible active compounds of HXP and their potential therapeutic targets; the results of anti-inflammatory genes associated with MIRI were obtained from GeneCards, Drugbank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Datebase (TTD) databases was performed; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the intersected targets; molecular docking was performed using AutoDock Tools. Western blot was used to detect the protein expression of Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NFκB)/NOD-like receptor protein 3 (NLRP3).@*RESULTS@#Compared with the model group, all doses of HXP significantly reduced the levels of LDH, CK and CK-MB (P<0.05, P<0.01); HXP significantly increased serum activity of SOD (P<0.05, P<0.01); all doses of HXP significantly reduced the levels of hs-CRP and IL-1β (P<0.05, P<0.01) and the myocardial infarction rate and myocardial no-reflow rate (P<0.01). GO enrichment analysis mainly involved positive regulation of gene expression, extracellular space and identical protein binding, KEGG pathway enrichment mainly involved PI3K-Akt signaling pathway and lipid and atherosclerosis. Molecular docking results showed that kaempferol and luteolin had a better affinity with TLR4, NFκB and NLRP3 molecules. The protein expressions of TLR4, NFκB and NLRP3 were reduced in the HXP group (P<0.01).@*CONCLUSIONS@#HXP has a significant protective effect on myocardial ischemia-reperfusion injury in rats, and its effect may be related to the inhibition of redox response and reduction of the inflammatory response by inhibiting the TLR4NFκB/NLRP3 signaling pathway.

Ocular images for neurodegenerative disease analysis / 国际眼科杂志(Guoji Yanke Zazhi)

@#Retina and optic nerve both originate in brain, therefore they have the similar structure and functional characteristics of the brain. Exploring the performance of the central optic nervous disorder on the retina will be beneficial to uncovering the interaction mechanism between brain and eye. As an extension of the central nervous system, the retina contains ganglion cell, a special neuron, whose axon form the optic nerve and has access into the central nervous system. Therefore, the retina can be used as a mirror reflecting neurodegenerative diseases structurally and functionally. With the development of imaging technology, optical coherence tomography(angiography)has become the mainstream tool for ophthalmological clinical diagnosis due to its easy operation and low cost. In recent years, discovering biomarkers of neurodegenerative diseases, especially Alzheimer's disease, Parkinson's disease, multiple sclerosis and so on, in the retinal optical coherence tomography images has gradually become an emerging research direction. In this review, we summarized the research progress of neurodegenerative diseases analysis based on the retinal images in the past decade, and provide a prospect to inspire further research as far as possible.

Assessment of macular vascular network after panretinal photocoagulation in the patients with diabetic retinopathy by OCTA / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To evaluate the differences of macular vascular network measured by optical coherence tomography angiography(OCTA)between severe non-proliferative diabetic retinopathy(S-NPDR)eyes and health eyes, and explore the changes of these OCTA characteristics in patients with S-NPDR before and after panretinal photocoagulation(PRP).<p>METHODS: This was a prospective study including 31 eyes from 18 consecutive patients with S-NPDR and 31 eyes of healthy subjects. We measured macular vascular density and foveal avascular zone(FAZ)area and volume by an OCTA device.<p>RESULTS: Compared to the normal control group, in superficial retinal capillary plexus(SCP), macular vascular density decreased in S-NPDR group, except foveal vascular density unchanged. Consistently, in deep retinal capillary plexus(DCP), macular vascular density was also lower in S-NPDR group. In addition, FAZ area and volume expanded in S-NPDR eyes. At 6mo post-PRP in S-NPDR eyes, foveal SCP and DCP densities increased significantly, while FAZ area and volume decreased. At 3mo post-PRP, only foveal vascular density in DCP increased. The changes of foveal SCP and DCP densities as well as FAZ area and volume were not statically significant at 1mo post-PRP.<p>CONCLUSION: Macular vascular network was impaired in S-NPDR assessed by OCTA. Although OCTA parameters were not significantly affected by PRP in 1 and 3mo period, at 6mo follow-up parameters became significant after PRP.

Mechanisms of pruritus in atopic dermatitis / 中华皮肤科杂志

Pruritus in atopic dermatitis (AD) is typical non-histaminergic itch involving complex nerve pathways. A variety of cytokines and neuropeptides, skin barrier dysfunction and skin microbiome imbalance are also involved in the generation and transmission of itching-relatd signals. This review focuses on main research progress in the pathogenesis and treatment of pruritus in AD in recent years.

Correlation between cervical vertigo and vestibular function evaluated by vestibular evoked myogenic potentials / 中国骨伤

OBJECTIVE@#To analyze the relationship between cervical vertigo and vestibular function evaluated by vestibular evoked myogenic potentials(VEMPs) and analyze the correlations between cervical vertigo and vestibular dysfunction, discuss the related factors of cervical vertigo and guide the clinical treatment of patients with cervical vertigo.@*METHODS@#A total of 75 patients with cervical vertigo as the main complaint in the outpatient clinic of the Second Hospital of Shanxi Medical University from August 2019 to July 2020 were set as the diseased group, and 60 patients without cervical and vestibular related diseases in the hospital were selected to set as non-diseased group. The age of diseased group was 12 to 70 years with an average of (46.40±10.91) years, including 25 males and 50 females;and the age of non-diseased group was 22 to 60 years with an average of(43.78±7.75) years, including 19 males and 51 females. VEMPs were performed in the two groups. The data of VEMPs were collected and the results were compared and analyzed. The patients with abnormal cervical myogenic vestibular evoked myogenic potential (cVEMP) were divided into light, moderate and severe groups. The correlation between VEMPs and cervical vertigo and its severity were analyzed by statistical method.@*RESULTS@#(1)The severity of cervical vertigo in diseased group:33 cases of mild, 34 cases of moderate, 8 cases of severe; cVEMP examination:62 cases were positive and 13 cases were negative, including 13 cases of mild, 33 cases of moderate, 16 cases of severe. The cVEMP of non-diseased group:4 cases were positive and 56 cases were negative.(2) The level of cVEMP in diseased group was higher than that in non-diseased group (P<0.001). It can be considered that there was a correlation between cervical vertigo and vestibular function.(3)The correlation between the level of cVEMP and the level of cervical vertigo in diseased group was analyzed. The Spearman rank sum test was used, and the correlation coefficient was 0.687, which was statistically significant (P<0.05). And it can be considered that the two indicators have a high degree of correlation.@*CONCLUSION@#It is feasible to evaluate the relationship between cervical vertigo and vestibular function by VEMPs. For patients with cervical vertigo, the higher the severity, the greater the positive rate of VEMPs, which indicates that it has a greater impact on vestibular function. The treatment of patients with cervical vertigo should be the combination of cervical rehabilitation and vestibular function.

Acute gallstone pancreatitis caused by duodenal papillary impacted stone: a study on its risk factors based on ERCP findings / 中华肝胆外科杂志

Objective:To study the risk factors of acute gallstone pancreatitis (AGP) caused by impaction of duodenal papilla stones based on ERCP findings to provide evidence on prevention of AGP caused by stone impaction.Methods:The data of 304 patients with duodenal papilla stone impaction who were treated by ERCP at the Integrated Chinese and Western Medicine Hospital of Tianjin University from January 2009 to December 2020 were analyzed retrospectively. There were 177 males and 127 females, with a median age of 65.0 years. These patients were divided into the AGP group ( n=174) and the non-AGP group ( n=130) according to whether they developed acute pancreatitis before hospitalization. The analysis was performed on perioperative data. Multivariate logistic regression analysis was used to detect risk factors of AGP in patients with duodenal papillary stone impaction. Results:Multivariate logistic analysis showed that acute cholangitis ( OR=2.114, 95% CI: 1.279-3.494, P<0.05) and impacted stones ≤5 mm ( OR=1.738, 95% CI: 1.064-2.840, P<0.05) were independent risk factors of duodenal papillary stone impaction complicated with AGP. No perforation and death related to ERCP treatment occurred in both groups. The symptom alleviating time of patients in the AGP versus the non-AGP groups was (2.67±1.19) versus (1.88±0.88) d respectively ( t=-6.321, P<0.001). Conclusion:Among patients with duodenal papilla impacted stones, acute cholangitis and impacted stones ≤5 mm were risk factors of developing AGP, and ERCP should be carried out as early as possible.

Research progress on Chinese medicinal material-derived active polypeptides against ischemic cardiovascular and cerebrovascular diseases / 中国中药杂志

Ischemic cardiovascular and cerebrovascular diseases threatening human health and survival have high morbidity and mortality. The common cause of them is reduced blood supply caused by vascular stenosis, atherosclerosis, and infarction. However,the pathological processes of ischemic cardiovascular and cerebrovascular diseases are complex, involving oxidative stress, calcium overload, inflammation, apoptosis, autophagy and other mechanisms. Protein drugs such as recombinant tissue plasminogen activator(rt-PA) and urokinase have been proved with excellent therapeutic effects and huge economic and social benefits in the clinical treatment and interventional therapy. Among them, peptide drugs have shown unique advantages and potential prospects owing to their strong biological activity, high target specificity, biochemical diversity, and low toxicity. Chinese medicinal materials, characterized by multi-component and multi-target therapy, have also shown excellent clinical efficacy against ischemic cardiovascular and cerebrovascular diseases. However, the research and development of related peptides in Chinese medicinal materials is at the initial stage. Therefore, this paper reviewed the targets and action mechanisms of a variety of Chinese medicinal material-derived polypeptides with activities against ischemic cardiovascular and cerebrovascular diseases, aiming to provide support for the in-depth research as well as the clinical development and application of these polypeptides.

Comparative study of dose distributions calculated by dual optimization modes of Monaco system by volumetric modulated arc therapy of nasopharyngeal carcinoma / 中国辐射卫生

Objective To compare the dosimetric differences in volumetric modulated arc therapy (VMAT) of Monaco planning system for nasopharyngeal carcinoma between Pareto and Constrained optimization in order to provide a reference for future mode selection. Methods Select 20 patients with nasopharyngeal carcinoma whom were calculated by Pareto and Constrained modes in the same CT image. Prescription dose of target PGTV, PTV1 and PTV2 was 70.29、60.39 and 54.45 Gy with 33 fractions, 5 times a week. The differences in target dose, organs at-risk dose, monitor units and segments were compared in the condition of 95% of the target volume reached the prescribed dose. Results Compared with Pareto group, Constrained group achieved a better HI and CI. CI of PGTV and PTV1 signed statistical differences (P < 0.05). Dose of OARs in Constrained group were all lower than those in Pareto group except Optical-l and lens-l. The differences of spinal cord prv dose and V30 of Parotid-r between two groups was significant (P < 0.05) while the differences of monitor units and segments between two groups was not significant (P > 0.05). Conclusion The length of middle turbinate is negatively correlated with the occurrence and severity of CMS. There is no significant correlation between the degree of curling and the occurrence of CMS, but patients with lower degree of curling of middle turbinate may have more serious CMS.

Role of microRNAs in progress of liver Hbrosis / 中国药理学通报

Liver fibrosis is one of the main diseases with high morbidity and mortality worldwide. It is the common pathological results of several chronic irritant disease such as viral hepatitis ，alcohol abuse, autoimmune diseases, metabolic diseases and cholestatic liver diseases and will further develop into cirrhosis ，liver failure, portal hypertension and even death. The excessive accumulation of extracellular matrix (ECM) that leads to disorder of liver structure is the main factor in the development of liver fibrosis. MicroRNAs are a class of 2225 nt endogenous noncoding small RNAs. Sufficient studies have shown that the abnormal expression of microRNAs is closely related to the progression of liver fibrosis. In this review, we summarize the regulatory effects of microRNAs discovered in recent years on the activation ，proliferation apoptosis and senescence of HSCs in liver fibrosisand the underlying mechanisms, putting forward the prospect.

IL-17A exacerbates diabetic retinopathy by impairing Müller cell function via Act1 signaling

Diabetic retinopathy (DR), one of the most serious complications of diabetes, has been associated with inflammatory processes. We have recently reported that interleukin (IL)-17A, a proinflammatory cytokine, is increased in the plasma of diabetic patients. Further investigation is required to clarify the role of IL-17A in DR. Ins2(Akita) (Akita) diabetic mice and high-glucose (HG)-treated primary Müller cells were used to mimic DR-like pathology. Diabetes induced retinal expression of IL-17A and IL-17 receptor A (IL-17RA) in Müller cells in contrast to ganglion cells. Further evidence demonstrated that retinal Müller cells cultured in vitro increased IL-17A and IL-17RA expression as well as IL-17A secretion in the HG condition. In both the HG-treated Müller cells and Akita mouse retina, the Act1/TRAF6/IKK/NF-κB signaling pathway was activated. IL-17A further enhanced inflammatory signaling activation, whereas Act1 knockdown or IKK inhibition blocked the downstream signaling activation by IL-17A. HG- and diabetes-induced Müller cell activation and dysfunction, as determined by increased glial fibrillary acidic protein, vascular endothelial growth factor and glutamate levels and decreased glutamine synthetase and excitatory amino acid transporter-1 expression, were exacerbated by IL-17A; however, they were alleviated by Act1 knockdown or IKK inhibition. In addition, IL-17A intravitreal injection aggravated diabetes-induced retinal vascular leukostasis, vascular leakage and ganglion cell apoptosis, whereas Act1 silencing or anti-IL-17A monoclonal antibody ameliorated the retinal vascular damage and neuronal cell apoptosis. These findings establish that IL-17A exacerbates DR-like pathology by the promotion of Müller cell functional impairment via Act1 signaling.

Multivariate Analysis of the “Small for Gestational Age” in Twins / 中国医科大学学报

Objective to analyze the influence obstetric factors of the small for gestational age(SGA)in twins,so as to direct the clinical prenatal supervision in clinic. Methods A retrospective study of the SGA was performed,the general data of 1 514 patients admitted in obstetrics and gyne-cology of Shengjing Hospital during 2001 to 2014 were analyzed by Logistic regression analysis. Results the incidence of the SGA in twins was 10.89%. the protective factors were male fetus,assisted reproductive technology(ARt)and gestational diabetes mellitus(GDM). the risk factors were the female fetus and hypertensive disorders in pregnancy. Conclusion the gender of fetus,assisted reproductive technology(ARt),gestation-al diabetes mellitus(GDM),hypertensive disorder complicating pregnancy are the influential factors of the SGA in twins. We recommend a further pre-pregnancy and pregnancy care which is of significance for the prevention of SGA.

The study on pathological changes of tau protein in the APP/tau/PS1 triple transgenic Alzheimer's disease mice / 中华老年医学杂志

Objective To identify the genotype of the APP/tau/PS1 triple transgenic Alzheimer's disease (AD) mice,and investigate the pathological changes of tau protein in the pathogenic process.Methods Using specific primers of PS1,APP,tau gene,the genotypes of the triple transgenic AD mice were identified.Expression of tau protein in hippocampal tissue of mouse model aged 2,4,8 month was detected by immunohistochemistry.The expression of tau and its hyperphosphorylation in different sites in the hippocampal tissue and different month old mice was detected by Western blotting.Results PCR amplification fragment of 960 bp,530 bp and 400 bp of transgenic mouse genome were the expected size of APP,PS1,tau,respectively.Expression of tau in hippocampal CA3 region was increased obviously in the 8 month old mice.Compared with the normal wild-type mice,the expressions of tau and phosphorylation of pS262,pS404 and pS202 were increased significantly in hippocampus tissue of the transgenic mice (P＜0.01).Expression of tau were significantly higher in 8-and 12-monthsold mice than in 2 months-old mice (P ＜ 0.01).Phosphorylation level of pS404 and Ps202 was significantly increased since 2-months-old in transgenic mouse compared to the wild type mouse (P＜0.01),and in 8-monthold mice,there was also a significant increase as compared to that in 2 month-old mice (P＜0.01).As to the phosphorylation level of pSs262,the significant increase did not appear until 12 months old in transgenic mouse as compared to the wild type mouse (P＜0.01).Conclusions The triple transgenic mice can stably express the APP/tau/PS1 gene.The transgenic animals can be a useful model with the pathological features of tau of AD.The phosphorylation level of tau in different site increases in different time,which will provide useful research reference in Alzheimer's disease pathology and medication research.