AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

Screening of Proteins Interacting with Nonstructural 1 Protein of H5N1 Avian Influenza Virus from T7-phage Display Library

Avian influenza virus（AIV） nonstructural 1（NS1） gene was amplified by real-time polymerse chain reac tion（RT-PCR） and inserted into pET28a, then transformed into E. coli BL21（DE3） competent cell. With the induction of isopropyl-β-D-thiogalactoside（IPTG） and the purification of Ni-NTA column, we finally obtained purified NS1 protein. T7-phage display system was used to screen the proteins that interacted with NS1 from lung cell cDNA li brary. The selected positive clones were identified by DNA sequencing and analyzed by BLAST program in Gene Bank. Two proteins were obtained as NS1 binding proteins, Homo sapiens nucleolar and coiled-body phosphoprotein 1（NOLC1） and Homo sapiens similar to colon cancer-associated antigen. By co-immunoprecipitation and other me thods, Homo sapiens NOLC1 was found to interact with the NS1 protein, the results would provide the basis for fur ther studying biological function of NS1 protein.

Calcium/calmodulin modulates salt responses by binding a novel interacting protein SAMS1 in peanut(Arachis hypogaea L.)

The Ca^(2+)/CaM signal transduction pathway helps plants adapt to environmental stress. However, our knowledge on the functional proteins of C^(2+)/CaM pathway in peanut(Arachis hypogeae L.) remains limited. In the present study, a novel calmodulin 4(CaM4)-binding protein S-adenosyl-methionine synthetase 1(SAMS1) in peanut was identified using a yeast two-hybrid assay. Expression of AhSAMS1was induced by Ca^(2+), ABA, and salt stress. To elucidate the function of AhSAMS1, physiological and phenotypic analyses were performed with wild-type and transgenic materials. Overexpression of AhSAMS1increased spermidine and spermidine synthesis while decreased the contents of ethylene, thereby eliminating excessive reactive oxygen species(ROS) in transgenic lines under salt stress. AhSAMS1 reduced uptake of Na+and leakage of K+from mesophyll cells, and was less sensitive to salt stress during early seedling growth, in agreement with the induction of SOS and NHX genes Transcriptomics combined with epigenetic regulation uncovered relationships between differentially expressed genes and differentially methylated regions, which raised the salt tolerance and plants growth. Our findings support a model in which the role of AhSAMS1 in the ROS-dependent regulation of ion homeostasis was enhanced by Ca^(2+)/CaM while AhSAMS1-induced methylation was regulated by CaM, thus providing a new strategy for increasing the tolerance of plants to salt stress.

MicroRNA-760 acts as a tumor suppressor in gastric cancer development via inhibiting G-protein-coupled receptor kinase interacting protein-1 transcription

BACKGROUND Gastric cancer(GC)has become a serious threat to people's health.Accumulative evidence reveals that dysregulation of numerous microRNAs(miRNAs)has been found during malignant formation.So far,the role of microRNA-760(miR-760)in the development of GC is largely unknown.AIM To measure the expression level of miR-760 in GC and investigate its role in gastric tumorigenesis.METHODS Real-time quantitative polymerase chain reaction and Western blot analysis were used to measure the expression of miR-760 and G-protein-coupled receptor kinase interacting protein-1(GIT1).Cell growth was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT)and cell colony formation assays.Apoptosis was assessed by flow cytometric analysis.The relationship between miR-760 and GIT1 was verified by luciferase reporter assay.RESULTS The results showed that the expression of miR-760 was decreased in GC and associated with poor clinical outcomes in GC patients.Furthermore,miR-760 restrained cell proliferation and cell colony formation and induced apoptosis in GC cells.In addition,miR-760 directly targeted GIT1 and negatively regulated its expression in GC.GIT1 was upregulated in GC and predicted a worse prognosis in GC patients.We also found that upregulation of GIT1 weakened the inhibitory CONCLUSION In conclusion,miR-760 targets GIT1 to inhibit cell growth and promote apoptosis in GC cells.Our data demonstrate that miR-760 may be a potential target for the treatment of GC.

Correlation between receptor-interacting protein 140 expression and directed differentiation of human embryonic stem cells into neural stem cells

Overexpression of receptor-interacting protein 140（RIP140） promotes neuronal differentiation of N2 a cells via extracellular regulated kinase 1/2（ERK1/2） signaling.However,involvement of RIP140 in human neural differentiation remains unclear.We found both RIP140 and ERK1/2 expression increased during neural differentiation of H1 human embryonic stem cells.Moreover,RIP140 negatively correlated with stem cell markers Oct4 and Sox2 during early stages of neural differentiation,and positively correlated with the neural stem cell marker Nestin during later stages.Thus,ERK1/2 signaling may provide the molecular mechanism by which RIP140 takes part in neural differentiation to eventually affect the number of neurons produced.

Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions

Active host-pathogen interactions take place during infection of human immunodeficiency virus type 1 (HIV-1). Outcomes of these interactions determine the efficiency of viral infection and subsequent disease progression. HIV- infected cells respond to viral invasion with various defensive strategies such as innate, cellular and humoral immune antiviral mechanisms. On the other hand, the virus has also developed various offensive tactics to suppress these host cellular responses. Among many of the viral offensive strategies, HIV-1 viral auxiliary proteins (Tat, Rev, Nef, Vif, Vpr and Vpu) play important roles in the host-pathogen interaction and thus have significant impacts on the outcome of HIV infection. One of the best examples is the interaction of Vif with a host cytidine deaminase APOBEC3G. Although specific roles of other auxiliary proteins are not as well described as Vif-APOBEC3G interaction, it is the goal of this brief review to summarize some of the preliminary findings with the hope to stimulate further discussion and investiga- tion in this exhilarating area of research.

Thioredoxin interacting protein,a key molecular switch between oxidative stress and sterile inflammation in cellular response

Tissue and systemic inflammation have been the main culprit behind the cellular response to multiple insults and maintaining homeostasis.Obesity is an independent disease state that has been reported as a common risk factor for multiple metabolic and microvascular diseases including nonalcoholic fatty liver disease(NAFLD),retinopathy,critical limb ischemia,and impaired angiogenesis.Sterile inflammation driven by high-fat diet,increased formation of reactive oxygen species,alteration of intracellular calcium level and associated release of inflammatory mediators,are the main common underlying forces in the pathophysiology of NAFLD,ischemic retinopathy,stroke,and aging brain.This work aims to examine the contribution of the pro-oxidative and pro-inflammatory thioredoxin interacting protein(TXNIP)to the expression and activation of NLRP3-inflammasome resulting in initiation or exacerbation of sterile inflammation in these disease states.Finally,the potential for TXNIP as a therapeutic target and whether TXNIP expression can be modulated using natural antioxidants or repurposing other drugs will be discussed.

Interaction among Rb/p16, Rb/E2F1 and HDAC1 Proteins in Gallbladder Carcinoma

The mechanism and interaction among Rb/p16, Rb/E2F1 and HDAC1 proteins in gallbladder carcinoma were investigated. By using the immunoprecipitation method, the interactions among Rb, p16, E2F1, HDAC1 proteins in gallbladder carcinoma cell line （Mz-ChA-1） were studied. It was found that there were Rb and E2F1 proteins in the precipitates with anti-HDAC1, and there were HDAC1 and E2F1 proteins in the precipitate with anti-Rb. It was concluded that there are specific interactions among Rb, HDAC1 and E2F1 proteins in gallbladder carcinoma, indicating the existence of the direct Rb/E2F1/HDAC1 signal transduction pathway. There is no direct relationship between p16 proteins with Rb, HDAC1, and E2F1 proteins.

Dengue virus non-structural 1 protein interacts with heterogeneous nuclear ribonucleoprotein H in human monocytic cells

Objective: To study protein-protein interaction between heterogeneous nuclear ribonucleoprotein H(hn RNP H) and Dengue virus(DENV) proteins. Methods: DENV proteins were screened against the host hn RNP H protein, in order to identify the host-viral protein-protein interactions in DENV infected THP-1 cells by co-immunoprecipitation. The co-localization of the interacting proteins was further confirmed by immunofluorescence microscopy. Results: The host protein hn RNP H was found to interact with DENV nonstructural 1 protein and help the virus to multiply in the cell. Conclusions: The non-structural 1 glycoprotein is a key modulator of host immune response and is also involved in viral replication. Therefore, disruption of this key interaction between hn RNP H and DENV nonstructural 1 could be an important therapeutic strategy for management of DENV infection.

Ferritin,heavy polypeptide 1 interacts with fragile X-related protein 1

Fragile X-related protein 1（FXR1P） is a member of the FXR gene family,which also includes fragile X mental retardation protein and fragile X-related protein 2（FXR2P）.To understand the functions of FXR1P,we screened FXR1P-interacting proteins using a yeast two-hybrid system.FXR1P was fused to pGBKT7 and used as the bait to screen a human fetal brain cDNA library.This screening revealed 10 FXR1P-interacting proteins including FTH1.FTH1 encodes Homo sapiens ferritin,heavy polypeptide 1.The interaction between FXR1P and FTH1 was confirmed by retesting in yeast using both a β-galactosidase assay and growth studies on selective media.A co-immunoprecipitation assay in mammalian cells further confirmed the FXR1P/FTH1 interaction.Moreover,the results revealed that FTH1 colocalized with FXR1P in the cytoplasm around the nucleus in mammalian cells.The present findings suggest that FXR1P plays an important role in iron metabolism in the brain by interacting with FTH1.This provides clues for elucidating the relationship between FXR1P function and fragile X syndrome.

Screening proteins that interact with mutant superoxide dismutase 1 from familial amyotrophic lateral sclerosis using a yeast two-hybrid system

The present study screened a human fetal brain cDNA library to find the proteins that interact with mutant superoxide dismutase 1 （SOD1） using a yeast two-hybrid system. Using BLAST software, 15 real proteins which interacted with mutant SOD1 were obtained, including 8 known proteins （protein tyrosine-phosphatase non-receptor type 2, TBCl D4, protein kinase family, splicing factor, arginine/serine-rich 2, SRC protein tyrosine kinase Fyn, β-sarcoglycan; glycine receptor a2, microtubule associated protein/microtubule affinity-regulating kinase 1, ferritin H chain）, and 7 unknown proteins. Results demonstrated interaction of mutant SOD1 with microtubule associated protein/microtubule affinity-regulating kinase 1 and β-sarcoglycan.

TNIP1基因单核苷酸多态性及其mRNA表达水平与老年慢性心力衰竭患者肺部感染的相关性分析

目的探讨肿瘤坏死因子诱导蛋白3相互作用蛋白1(TNFAIP3-interacting protein 1,TNIP1)基因单核苷酸多态性及其mRNA表达水平与老年慢性心力衰竭患者肺部感染的相关性。方法选择2019年10月至2022年10月于上海建工医院重症医学科就诊的130例老年慢性心力衰竭患者作为研究对象,根据是否于院内发生肺部感染分为感染组(32例)和未感染组(98例)。对TNIP1基因的两个SNP位点rs6889239(T>C)、rs17728338(A>G)进行基因分型,并检测外周血TNIP1基因的mRNA表达水平。结果TNIP1基因rs6889239位点在感染组和非感染组之间的基因型分布以及等位基因频率的差异均无统计学意义(P>0.05);两组的rs17728338位点AA、AG、GG基因型分布比较差异有统计学意义(P<0.05),且感染组等位基因G的频率显著高于未感染组(P<0.05)。相较于未感染组,感染组患者的外周血TNIP1基因mRNA表达水平显著增加,差异有统计学意义(P<0.001)。受试者工作特征(Receiver operating characteristic,ROC)曲线分析结果显示外周血TNIP1基因表达水平预测慢性心力衰竭患者发生肺部感染的灵敏度和特异度分别为71.9%和95.9%。感染组和非感染组TNIP1基因rs6889239位点不同基因型患者的外周血TNIP1基因的表达水平比较差异均无统计学意义(P>0.05),而rs17728338位点不同基因型患者的外周血TNIP1基因表达水平比较差异有统计学意义(P<0.05)。结论TNIP1基因rs17728338表达水平与老年慢性心力衰竭患者发生肺部感染有关。

受体相互作用蛋白激酶1调节癌症进展和免疫反应的研究现状

受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)是一种多结构域丝氨酸/苏氨酸蛋白激酶。它通过磷酸化特定的蛋白质,引起下游的信号转导和生物效应。近年来,随着对RIPK1的深入研究,学者发现其在自身免疫性疾病、神经退行性疾病,以及多种实体瘤和血液肿瘤中具有重要意义。一方面,RIPK1通过激活特定通路如核因子-κB(nuclear factor-κB,NF-κB)和丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等促进细胞存活及炎症反应。另一方面,RIPK1通过与胱天蛋白酶-8(cysteinyl aspartate specific proteinase-8,caspase-8)作用促进凋亡,或与RIPK3和混合谱系激酶结构域样假激酶(mixed lineage kinase domain-like protein,MLKL)作用促进坏死性凋亡的发生。RIPK1作为上游信号在不同肿瘤患者中表达水平不同。其支架功能和激酶活性可以调节癌症进展,也可以启动机体适应性免疫,抑制肿瘤进展;此外,还能产生免疫抑制性肿瘤微环境而促进肿瘤的发展。其双重作用在调节癌症的发生、发展及机体免疫反应方面都有所展现,可以作为新的治疗靶点控制癌症进展。该文从RIPK1的结构入手,深入探讨其功能,特别是其在调节癌症进展和免疫反应方面的功能,为癌症靶向药物的开发提供新的思路。

瑞马唑仑调节HIF-1α/BNIP3信号通路对OGD/R诱导神经细胞自噬和凋亡的影响

目的探讨瑞马唑仑对OGD/R诱导的神经细胞自噬和凋亡的影响及作用机制。方法体外培养小鼠海马神经元细胞(HT22)并进行神经细胞氧糖剥夺/再复氧(OGD/R),筛选实验用瑞马唑仑浓度;将HT22细胞分为对照组、OGD/R组、瑞马唑仑组、2-ME2组、瑞马唑仑+2-ME2组;CCK8法检测5组HT22细胞活力;流式细胞术检测5组HT22细胞凋亡率;透射电子显微镜观察5组HT22细胞自噬小体的形成;Western blot检测5组HT22细胞HIF-1α、BNIP3、LC3-Ⅱ/LC3-Ⅰ的表达。结果确定实验用瑞马唑仑浓度为50μg/mL;与对照组比较,OGD/R组HT22细胞OD450值、HIF-1α、BNIP3、LC3-Ⅱ/LC3-Ⅰ蛋白水平下调,凋亡率上调(P<0.05);与OGD/R组比较,瑞马唑仑组HT22细胞自噬小体增加,OD450值、HIF-1α、BNIP3、LC3-Ⅱ/LC3-Ⅰ蛋白水平上调,凋亡率下调(P<0.05);2-ME2组HT22细胞OD450值、HIF-1α、BNIP3、LC3-Ⅱ/LC3-Ⅰ蛋白水平下调,凋亡率上调(P<0.05)。与瑞马唑仑组比较,瑞马唑仑+2-ME2组HT22细胞自噬小体数量减少,OD450值、HIF-1α、BNIP3、LC3-Ⅱ/LC3-Ⅰ蛋白水平下调,凋亡率上调(P<0.05);与2-ME2组比较,瑞马唑仑+2-ME2组HT22细胞OD450值、HIF-1α、BNIP3、LC3-Ⅱ/LC3-Ⅰ蛋白水平上调,凋亡率下调(P<0.05)。结论瑞马唑仑可通过激活HIF-1α/BNIP3信号通路促进OGD/R诱导的神经细胞自噬,抑制细胞凋亡,从而减轻OGD/R诱导的神经细胞损伤。

RNA干扰受体相互作用蛋白激酶1基因表达对肾透明细胞癌生物活性的影响

目的探讨受体相互作用蛋白激酶1(RIPK1)对肾透明细胞癌(ccRCC)生物功能的影响及机制。方法通过RNA干扰技术降低RIPK1在ccRCC中的表达后,光镜观察细胞形态变化,CCK-8法检测细胞增殖变化情况,Transwell细胞迁移实验检测细胞迁移能力的变化,流式细胞仪检测细胞发生凋亡、坏死水平,Western blot法检测cleaved caspase-3、混合谱系蛋白激酶样结构域(MLKL)和RIPK3表达变化。结果小干扰RNA(siRNA)干扰48 h后,RIPK1-siRNA组细胞增殖吸光度值(0.563±0.042)低于NC-siRNA组(0.944±0.039;t=11.550,P=0.003);siRNA干扰72 h后,RIPK1-siRNA组吸光度值(0.408±0.019)低于NC-siRNA组(1.717±0.108;t=20.620,P<0.001)。与NC-siRNA组(72.000±12.120)比较,RIPK1-siRNA组(31.660±10.020)ccRCC细胞的迁移数量明显减少(t=4.442,P=0.011)。与NC-siRNA组(0.360±0.090、0.510±0.060、0.880±0.070)比较,RIPK1-siRNA组ccRCC细胞内cleaved caspase3、MLKL、RIPK3表达明显增加(0.780±0.070、1.490±0.100、1.680±0.130;t=6.380,P=0.003;t=8.656,P=0.001;t=14.150,P=0.001)。结论RIPK1是ccRCC内调控细胞增殖、死亡及迁移能力的重要基因,抑制RIPK1能够促进ccRCC发生凋亡及坏死性凋亡。

Inhibition of mouse acrosome reaction and sperm-zona pellucida binding by anti-human sperm membrane protein 1 antibody

Aim： To investigate the possible functions of human sperm membrane protein （hSMP-1） in the process of fertilization. Methods： A 576-bp cDNA fragment of HSD-1 gene coding for the extracellular domain of hSMP-1 was cloned and expressed. The localization of this protein on human and mouse sperm was determined by indirect immunofluorescent staining by using anti-recombinant hSMP-1 （anti-rhSMP-1） antibodies. Sperm acrosome reaction and spermzona pellucida （ZP） binding assay were carried out in 10-week-old BALB/c mice. Results： Recombinant hSMP-1 was successfully cloned and expressed. The expression of the native protein was limited on the acrosome of human and mouse sperm. Treatment of anti-rhSMP-1 antibodies significantly decreased the average number of sperms bound to each egg. Meanwhile, the percentage of acrosome reaction was decreased in comparison to pre-immune control after treatment with anti-rhSMP-1 （P 〈 0.05）. Conclusion： The results suggest that anti-rhSMP-1 antibody inhibited mouse acrosome reaction and sperm-ZP binding.

Hepatitis B Virus X Protein Upregulates Intracellular Calcium Signaling by Binding C-terminal of Orai1 Protein

Hepatitis B virus X(HBx)protein plays a pivotal role in the development of hepatitis B virus(HBV)-associated hepatocellular carcinoma.Although regulation of cytosolic calcium is essential for HBV replication and is mediated by HBx protein,the mechanism of HBx protein regulating intracellular calcium level remains poorly understood.The present study examined whether HBx protein elevated the intracellular calcium through interacting with storeoperated calcium entry(SOCE)components,Orai1 and stromal interaction molecule 1,and then identified the targets of HBx protein,with an attempt to understand the mechanism of HBx protein upsetting intracellular calcium homeostasis.By employing co-immunoprecipitation and GST-pull-down assay,we found that Orai1 protein interacted with HBx protein,and the C-terminus of Orai1 was implicated in the interaction.Confocal microscopy also revealed that HBx protein could co-localize with full-length Orai1 protein in HEK293 cells.Moreover,live cell calcium imaging exhibited that HBx protein elevated intracellular calcium,possibly by binding to SOCE components.Our results suggest that HBx protein binds to STIM1-Orai1 complexes to positively regulate the activity of plasma membrane store-operated calcium channels.

Gene environment interaction in periphery and brain converge to modulate behavioral outcomes:Insights from the SP1 transient early in life interference rat model

It is generally assumed that behavior results from an interaction between susceptible genes and environmental stimuli during critical life stages.The present article reviews the main theoretical and practical concepts in the research of gene environment interaction,emphasizing the need for models simulating real life complexity.We review a novel approach to study gene environment interaction in which a brief post-natal interference with the expression of multiple genes,by hindering the activity of the ubiquitous transcription factor specificity protein 1(Sp1) is followed by later-in-life exposure of rats to stress.Finally,this review discusses the role of peripheral processes in behavioral responses,with the Sp1 model as one example demonstrating how specific behavioral patterns are linked to modulations in both peripheral and central physiological processes.We suggest that models,which take into account the tripartite reciprocal interaction between the central nervous system,peripheral systems and environmental stimuli will advance our understanding of the complexity of behavior.

A Multiple Functional Protein:the Herpes Simplex Virus Type 1 Tegument Protein VP22

The herpes simplex virus type 1 （HSV-1） VP22, is one of the most abundant HSV-I tegument proteins with an average stoichiometry of 2 400 copies per virion and conserved among alphaherpesvirinae. Many functions are attributed to VP22, including nuclear localization, chromatin binding, microtubule binding, induction ofmicrotubule reorganization, intercellular transport, interaction with cellular proteins, such as template activating VP16, pU factor I （TAF-I） and nonmuscle myosin II A （NMIIA）, and viral proteins including pUS9 and pUL46, glycoprotein E （gE） and gD. Recently, many novel functions perform tegument protein ed by the HSV-1 VP22 protein have been shown, including promotion of protein synthesis at late times in infection, accumulation of a subset of viral mRNAs at early times in infection and possible transcriptional regulation function .

血塞泰对缺血性脑卒中大鼠STIM1、Orai1蛋白表达的影响

目的研究血塞泰对缺血性脑卒中(ischemic stroke,IS)大鼠基质相互作用分子1(stromal interaction molecule 1,STIM1)及钙释放激活钙通道蛋白1(calcium release-activated calcium channel protein 1,Orai1)的影响。方法选取60只SPF级雄性SD大鼠,随机分为假手术组10只、造模组50只,采用线栓法制备大脑中动脉栓塞(medial cerebral artery occlusion,MCAO)模型。采用随机数字表法将造模成功的41只大鼠分为模型组、血塞泰低剂量组(12.6 g/kg)、血塞泰中剂量组(25.2 g/kg)、血塞泰高剂量组(50.4 g/kg)和阿司匹林肠溶片组(18 mg/kg),其中血塞泰低剂量组9只,其余每组各8只;假手术组和模型组给予等量生理盐水灌胃。每组连续干预7 d。采用改良神经功能损伤评分(modified Neurological Severity Score,mNSS)评估各组大鼠神经功能损伤情况,TTC染色法检测大鼠脑组织的梗死面积,ELISA法测定大鼠血清中的白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)含量,RT-PCR检测脑组织中STIM1、Orai1 mRNA的表达,免疫共沉淀检测脑组织STIM1、Orai1的蛋白相对表达水平。结果与假手术组相比,模型组大鼠mNSS评分增加(P<0.01),脑梗死率增加(P<0.01),血清IL-6、TNF-α含量增加(P<0.01),脑组织STIM1、Orai1 mRNA表达水平和蛋白相对表达水平升高(P<0.01)。与模型组相比,血塞泰各剂量组和阿司匹林肠溶片组大鼠mNSS评分下降(P<0.05),血清IL-6、TNF-α含量下降(P<0.01),脑组织STIM1、Orai1 mRNA表达水平下降(P<0.01);血塞泰中、高剂量组和阿司匹林肠溶片组大鼠脑梗死率下降(P<0.01),脑组织STIM1、Orai1的蛋白相对表达水平降低(P<0.05,P<0.01)。与阿司匹林肠溶片组相比,血塞泰低剂量组脑梗死率增加(P<0.01),血清IL-6、TNF-α含量增加(P<0.01),脑组织STIM1、Orai1 mRNA表达水平增加(P<0.05);血塞泰中剂量组血清IL-6、TNF-α含量明显增加(P<0.01),脑组织STIM1、Orai1 mRNA表达水平下降(P<0.05,P<0.01);血塞泰高剂量组脑梗死率下降(P<0.01),血清IL-6、TNF-α含量明显下降(P<0.01),脑组织STIM1、Orai1 mRNA表达水平明显下降(P<0.01)。与血塞泰低、中剂量组相比,血塞泰高剂量组mNSS评分下降(P<0.05,P<0.01),脑梗死率下降(P<0.01),血清IL-6、TNF-α含量下降(P<0.01),脑组织STIM1、Orai1 mRNA表达水平下降(P<0.01)。结论血塞泰能够抑制STIM1、Orai1的表达及结合,减轻炎症反应,改善MCAO大鼠神经功能缺损与降低神经元损伤,从而发挥抗IS的作用。