Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

Inhibition of SLC26A4 regulated by electroacupuncture suppresses the progression of myocardial ischemia-reperfusion injury

Introduction:Myocardial ischemia-reperfusion(IR)injury has received widespread attention due to its damaging effects.Electroacupuncture(EA)pretreatment has preventive effects on myocardial IR injury.SLC26A4 is a Na+independent anion reverse transporter and has not been reported in myocardial IR injury.Objectives:Tofind potential genes that may be regulated by EA and explore the role of this gene in myocardial IR injury.Methods:RNA sequencing and bioinformatics analysis were performed to obtain the differentially expressed genes in the myocardial tissue of IR rats with EA pretreatment.Myocardial infarction size was detected by TTC staining.Serum CK,creatinine kinase-myocardial band,Cardiac troponin I,and lactate dehydrogenase levels were determined by ELISA.The effect of SLC26A4 on cardiomyocyte apoptosis was explored by TUNEL staining and western blotting.The effects of SLC26A4 on inflammation were determined by HE staining,ELISA,and real-time PCR.The effect of SLC26A4 on the NF-κB pathway was determined by western blotting.Results:SLC26A4 was up-regulated in IR rats but downregulated in IR rats with EA pretreatment.Compared with IR rats,those with SLC26A4 knockdown exhibited improved cardiac function according to decreased myocardial infarction size,reduced serum LDH/CK/CK-MB/cTnI levels,and elevated left ventricular ejection fraction and fractional shortening.SLC26A4 silencing inhibited myocardial inflammation,cell apoptosis,phosphorylation,and nuclear translocation of NF-κB p65.Conclusion:SLC26A4 exhibited promoting effects on myocardial IR injury,while the SLC26A4 knockdown had an inhibitory effect on the NF-κB pathway.These results further unveil the role of SLC26A4 in IR injury.

Integrated network pharmacology and metabolomics to explore the mechanisms of Shenzao dripping pill against chronic myocardial ischemia

Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac diseases.Nevertheless,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic effects.The objective of this study is to investigate the underlying mechanism of SZDP against chronic myocardial ischemia(CMI)in a rat model.Methods:In this study,we utilized electrocardiographic and echocardiographic detection along with pathological tissue analysis to evaluate the efficacy of SZDP.The integration of network pharmacology and metabolomics was conducted to investigate the mechanisms.Molecular docking and molecular dynamics simulations were used to validate the binding energy between the compounds of SZDP and the associated targets.Results:The results showed that SZDP was able to improve T wave voltage,reverse CMI abnormalities in ejection fraction and fractional shortening,and restore histopathological heart damage.Metabolomics results indicated that disturbances of metabolic profile in CMI rats were partly corrected after SZDP administration,mainly affecting purine metabolism.13-Docosenamide may be the potential metabolic biomarker of the therapeutic application of SZDP for CMI.Integrating network pharmacology and metabolomics,thiopurine S-methyltransferase(TPMT),xanthine dehydrogenase/oxidase(XDH),bifunctional purine biosynthesis protein ATIC(ATIC),and cytochrome p4501A1(CYP1A1)were identified as possible targets of SZDP to exert therapeutic effects by enhancing the metabolic levels of L-Tryptophan,Deoxyribose 1-phosphate and Phosphoribosyl formamidocarboxamide.Conclusion:SZDP has a therapeutic effect on CMI by regulating metabolite levels,acting on the targets of TMPT,XDH,ATIC,and CYP1A1,and reducing cardiomyocyte injury and myocardial fibrosis.

度伐利尤单抗联合PP化疗方案治疗Ⅲ期非小细胞肺癌患者的效果

目的:观察度伐利尤单抗联合PP化疗方案治疗Ⅲ期非小细胞肺癌(NSCLC)患者的效果。方法:回顾性分析2021年5月至2023年5月该院收治的66例Ⅲ期NSCLC患者临床资料,按治疗方案不同将其分为观察组和对照组各33例。对照组采用PP化疗方案治疗,观察组在对照组基础上联合度伐利尤单抗注射液治疗,比较两组疾病缓解率、KPS评分、癌症治疗功能评价系统-肺癌模块(FACT-L)评分、血清生化因子[Ⅳ型胶原蛋白α3(COL4A3)、G蛋白偶联受体相关分选蛋白1(GASP-1)]水平和不良反应发生率。结果:观察组疾病缓解率为60.61%,明显高于对照组的36.36%,差异有统计学意义(P<0.05);治疗后,两组KPS评分高于治疗前,且观察组高于对照组,两组FACT-L评分和血清COL4A3、GASP-1水平低于治疗前,且观察组低于对照组,差异均有统计学意义(P<0.05);治疗期间,两组腹泻、脱发、骨髓抑制、恶心等不良反应发生率比较,差异均无统计学意义(P>0.05)。结论:度伐利尤单抗联合PP化疗方案治疗Ⅲ期NSCLC患者可提高疾病缓解率和KPS评分,降低FACT-L评分及血清COL4A3、GASP-1水平,效果优于单纯PP化疗方案治疗。

枳PtrPP2C51基因克隆与非生物胁迫表达分析

克隆枳PP2C基因家族的PtrPP2C51基因,分析其在低温、高温和干旱等胁迫下的表达规律,探究其在非生物胁迫中的功能。以1年生枳苗为试材,从嫩叶克隆到PtrPP2C51基因cDNA序列,采用生物信息学方法对其进行分析,利用实时荧光定量PCR仪(qRT-PCR)检测枳苗在低温、高温和干旱(15%PEG-6000)处理下的PtrPP2C51基因表达模式。克隆获得PtrPP2C51基因编码区CDS序列长度为879 bp,编码292个氨基酸,其蛋白分子量为31.36 ku,理论等电点4.9,脂肪系数79.52,不稳定系数39.57,亲水性平均值-0.279。PtrPP2C51蛋白的二级结构中α-螺旋、β-转角、延伸链和无规则卷曲占比分别为40.07%、7.88%、18.15%和33.90%。PtrPP2C51蛋白与克里曼丁橘的PP2C蛋白在同一小分支上,亲缘关系最近。经低温(0℃)、高温(38℃)和干旱(15%PEG-6000)3种不同胁迫处理,PtrPP2C51基因的相对表达量均表现持续上调趋势,并且均在处理12 h时表达量达到最高值。PtrPP2C51基因可能参与枳的抗逆胁迫调控机制。

RCEP与CPTPP的比较和融合之道

当前,竞争政策在自由贸易协定中的地位愈发重要,约有五分之四的自由贸易协定涉及竞争条款。发达国家对于竞争法和区域自由贸易协定中的竞争条款都具有先进性,中国作为发展中国家对于竞争条款仍处于起步阶段,因此要在研究CPTPP等发达国家竞争条款的基础上,制定和完善符合发展中国家利益的竞争政策。

废弃PP纤维再生混凝土基本力学性能试验

目的 针对纤维体积掺量、长径比、再生骨料取代率等因素,探究废弃PP纤维对再生混凝土力学性能的影响,提高废弃纤维利用率。方法 以废弃PP打包带制成不同长径比的纤维作为筋材,以不同体积掺量与不同再生骨料取代率的再生混凝土混合制成11组废弃PP纤维再生混凝土试块,对其进行抗压和抗拉试验。结果 立方体抗压、抗拉强度最佳时的废弃PP纤维体积掺量为1.5%,长径比为47.85;废弃PP纤维再生混凝土的立方体抗压、抗拉强度与再生骨料取代率有关,其强度与再生骨料取代率近似呈线性关系。结论 废弃PP纤维的掺入可以提高再生混凝土的立方体抗压强度和抗拉强度。

三七总皂苷通过激活PPARα/Nrf2减轻内皮细胞屏障和功能损伤

目的研究三七总皂苷(PNS)对氧糖剥夺/复氧(OGD/R)诱导的内皮细胞屏障和功能损伤的保护作用,并探讨其作用机制。方法使用OGD/R诱导bEnd.3细胞以建立缺血再灌注损伤模型,同时设立对照组(Control)、模型组(OGD/R)、PNS高剂量组(OGD/R+PNS 400μg/mL)、PPARα抑制剂组(OGD/R+PNS 400μg/mL+PPARαinhibitor)和Nrf2抑制剂组(OGD/R+PNS 400μg/mL+Nrf2 inhibitor)。采用CCK-8检测bEnd.3细胞活性损伤,LDH试剂盒检测乳酸脱氢酶(LDH)表达,蛋白印迹法检测ZO-1、claudin-5、occludin表达;采用细胞划痕和细胞侵袭实验检测bEnd.3细胞侵袭和迁移的水平;借助小管形成实验检测bEnd.3细胞小管形成能力。结果PNS通过激活过氧化物酶体增殖物激活受体α/核因子E2相关因子2(PPARα/Nrf2)信号减轻OGD/R诱导的bEnd.3细胞活性损伤和内皮屏障损伤,抑制细胞迁移和侵袭能力,改善血管生成损伤。结论PNS通过激活PPARα/Nrf2信号减轻OGD/R诱导的内皮细胞屏障和功能损伤。

自成核行为在CF/PPS复合材料中的差异性与普适性

以半结晶高分子为基体的碳纤维增强热塑性复合材料,其基体的结晶行为将受到碳纤维表面性质与热历史的共同影响。当这种材料在经历反复加热冷却的热循环过程时,基体会产生自成核行为,其结晶过程变得更加复杂。通过三种T300级碳纤维分别制备了碳纤维增强聚苯硫醚(CF/PPS)复合材料,并探究了二次熔融温度与CF/PPS复合材料结晶行为的关系,揭示了不同碳纤维表面性质对CF/PPS复合材料自成核行为的影响。在此基础上阐明了CF/PPS复合材料基体自成核与CF异相成核的竞争关系。最后,通过冲压成型制得具有自成核行为的CF/PPS复合材料角片,验证了自成核对于CF/PPS复合材料二次热成型技术的有效性与重要性。

高岭土对APP/PER/PP复合材料性能的影响

以PP废玩具料(W-PP)为主材,高岭土(Kaol)、聚磷酸铵(APP)和季戊四醇(PER)为阻燃剂,通过熔融挤出制备一系列Kaol/APP/PER/W-PP复合材料,对复合材料的极限氧指数(LOI)、UL 94阻燃等级、力学性能和热变形温度(HDT)进行测试,并用锥形量热仪进行分析,结果表明,APP/PER添加后,复合材料的阻燃性能和HDT明显提高,力学强度逐渐降低;适量的Kaol和APP/PER具有较好的协同阻燃效果,而且,添加Kaol后,复合材料的力学性能和HDT明显提升,当在W-PP中同时加入3%的Kaol和25%的APP/PER时,复合材料的LOI为32.1%,阻燃达到UL 94(1.6 mm)V-0级,与单独添加相比,拉伸强度、弯曲模量、弯曲强度和缺口冲击强度均提高了28%APP/PER的性能分别提高了16.9%、15.0%、27.4%和31.3%。

Development of a new cerebral ischemia reperfusion model of Mongolian gerbils and standardized evaluation system

Background:The Mongolian gerbil is an excellent laboratory animal for preparing the cerebral ischemia model due to its inherent deficiency in the circle of Willis.However,the low incidence and unpredictability of symptoms are caused by numerous complex variant types of the circle.Additionally,the lack of an evaluation system for the cer-ebral ischemia/reperfusion(I/R)model of gerbils has shackled the application of this model.Methods:We created a symptom-oriented principle and detailed neurobehavioral scoring criteria.At different time points of reperfusion,we analyzed the alteration in locomotion by rotarod test and grip force score,infarct volume by triphenyltetrazo-lium chloride(TTC)staining,neuron loss using Nissl staining,and histological charac-teristics using hematoxylin-eosin(H&E)straining.Results:With a successful model rate of 56%,32 of the 57 gerbils operated by our method harbored typical features of cerebral I/R injury,and the mortality rate in the male gerbils was significantly higher than that in the female gerbils.The suc-cessfully prepared I/R gerbils demonstrated a significant reduction in motility and grip strength at 1 day after reperfusion;formed obvious infarction;exhibited typi-cal pathological features,such as tissue edema,neuronal atrophy and death,and vacuolated structures;and were partially recovered with the extension of reperfu-sion time.Conclusion:This study developed a new method for the unilateral common carotid artery ligation I/R model of gerbil and established a standardized evaluation system for this model,which could provide a new cerebral I/R model of gerbils with more practical applications.

PE/PP混杂纤维应变硬化碱激发复合材料力学性能研究

应变硬化碱激发复合材料(SHAAC)兼具低碳环保和高韧性的优点,但高昂的成本限制了其工程应用。为降低成本,研究采用PP纤维替代PE纤维,开发了一种混杂PE/PP纤维SHAAC,并通过轴压与轴拉试验及成本分析,探讨了不同PP纤维替代率(0%、25%、50%、75%和100%,体积分数)对混杂PE/PP纤维SHAAC的轴压、轴拉性能和成本的影响。结果表明:采用PP纤维替代PE纤维时,SHAAC的轴压、轴拉强度及裂缝控制能力随着纤维替代率的增加而降低,但在PP纤维替代率低于75%时,SHAAC仍可呈现伪应变硬化和多缝开裂现象;当PP纤维替代率为50%时,SHAAC极限拉伸应变最高(8.40%),且能保持较高的轴压和轴拉性能,同时成本可降低29.00%,且综合性能与成本比值最高。

PP1A与GSDME介导的结直肠癌细胞焦亡的临床意义

目的检测PP1A与GSDME在结直肠癌组织中的表达与CD8^(+)T淋巴细胞丰度,探讨PP1A与GSDME介导焦亡的相关性和临床意义。方法应用GEPIA数据库分析PP1A与GSDME在结直肠癌组织与正常组织中mRNA的表达。采用Western blot法检测结直肠癌组织与对应癌旁正常黏膜中PP1A蛋白表达水平,运用免疫组化法检测107例结直肠癌与癌旁正常黏膜中PP1A、GSDME蛋白的表达和CD8^(+)T淋巴细胞丰度。利用Spearman等级相关性分析PP1A、GSDME和CD8^(+)T淋巴细胞丰度的相关性。结果GEPIA数据库检索显示,PP1A与GSDME的mRNA在结直肠癌组织和正常组织中的表达差异有统计学意义(P<0.05)。Western blot法检测结果显示,结直肠癌组织中PP1A相对表达量明显高于癌旁组织(0.937 vs 0.643,P<0.001)。免疫组化结果显示,结直肠癌组织中PP1A的表达明显高于正常黏膜,而GSDME的表达明显低于正常黏膜(P<0.05),GSDME表达与结直肠癌患者年龄、临床分期和错配修复蛋白密切相关(P<0.05);CD8^(+)T细胞在癌浸润前沿的分布明显高于癌旁正常黏膜,且CD8^(+)T细胞在癌组织中的分布与pT分期、临床分期及淋巴结转移相关。Spearman相关性分析显示,PP1A与GSDME表达呈负相关(r=-0.196,P<0.05)。PP1A阳性结直肠癌患者的总生存期低于PP1A阴性患者(P<0.05),患者预后与分化程度、淋巴结转移、pT分期和临床分期相关。PP1A表达、肿瘤分化程度、临床分期、pT分期和淋巴结转移均是影响结直肠癌患者预后的独立危险因素。结论PP1A在结直肠癌中高表达,与GSDME介导的细胞焦亡呈负相关,两者表达差异性与结直肠癌的发生、发展及预后均密切相关,可作为判断结直肠癌患者预后的潜在指标,CD8^(+)T细胞的差异性分布可能与GSDME介导的细胞焦亡及肿瘤的发展相关。

The action mechanism by which C1q/tumor necrosis factor-related protein-6 alleviates cerebral ischemia/reperfusion injury in diabetic mice

Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.

Ginsenoside Rg1 protects against ischemia-induced neuron damage by regulating the rno-miRNA-27a-3p/PPARγaxis

A preliminary miRNA screening showed that expression levels of rno-miRNA-27a-3p were significantly increased in the serum and brain tissues of rats undergoing cerebral ischemia.In recent years,there is evidence of the protective capacity of the saponins extracted from panax ginseng and its primary active ingredient ginsenosideRg1oncerebral ischemic injury.Methods:Fetal rat neurons(FRNs)were cultured in glucose-and-serumfree medium and exposed to hypoxia to establish a cerebral ischemia model in vitro(oxygen and glucose deprivation model,OGD).Antioxidant indexes(CAT,SOD),inflammatory markers(MPO,TNF-αand IL-6),and the expression of apoptosis and proliferation associated proteins(NF kB-p65,Caspase 3-cleaved,BCL-2)were examined.Results:Pre-treatment of Rg1(30–100μg/mL)could effectively inhibit the decline of antioxidant indexes(CAT,SOD)and increase in inflammatory markers(MPO,TNF-αand IL-6),and effectively inhibited the apoptosis in FRNs induced by OGD in a gradient-dependent manner.The mechanism analysis showed that the role of Rg1 in protecting against ischemia-induced neuron damage depends on its indirect up-regulation of PPAR protein via suppression of rnomiRNA-27a-3p.Moreover,these effects of Rg1 could be reversed by exogenous rno-miRNA-27a-3p and PPAR gene silencing in FRNs exposed to OGD.Conclusion:To summarize,our study demonstrates that Rg1 could effectively attenuate neuronal damage caused by cerebral ischemia via the rno-miRNA-27a-3p/PPARγpathway.Further,clarification of the novel mechanism will certainly improve our previous understanding of the role of Rg1 and enhancing its level in treatments for alleviating ischemic brain injury.

PP/SEBS/HDPE复合材料的制备及性能研究

将氢化聚苯乙烯-丁二烯-聚苯乙烯(SEBS)与聚丙烯(PP)和聚乙烯(PE)通过双螺杆挤出机进行熔融共混后,制备得到PP/SEBS/HDPE三元共混物,采用冲击试验机、热重分析仪(TGA)、红外光谱仪、差示扫描量热仪(DSC)等手段对共混物的流动性能、力学性能、热性能、结晶行为、相容性等进行研究分析。结果表明,在PP/PE体系中,随着PE的增加,共混物的流动性逐渐变好,当PE含量为20%时,共混物的拉伸强度、冲击强度、断裂伸长率达到最高,此时其力学性能最优;在三元共混体系中,随着SEBS含量的增加,共混物的悬臂梁冲击强度大幅提高,当SEBS添加量为8%时,共混物的力学性能最优,因此最优体系为PP/20%HDPE/8%SEBS,此时共混物的相容性最好。

PPS+PTFE混纺针刺滤袋在燃煤电厂的应用分析

针对某燃煤电厂使用聚苯硫醚(PPS)滤袋不足一年时间即发生大面积破损的问题,制备面层不同PPS和聚四氟乙烯(PTFE)纤维质量比的PPS+PTFE混纺针刺滤袋,对其进行挂袋试验,并从面密度、透气性、拉伸性能、粉尘渗透情况、材质变化及微观形貌等方面分析使用前后PPS+PTFE混纺针刺滤袋的性能。根据试验数据进行PPS+PTFE混纺针刺滤袋使用寿命的预估分析,推算其剩余使用寿命。研究结果显示,制备的PPS+PTFE混纺针刺滤袋满足粉尘排放质量浓度长期低于10 mg/m3的要求;面层PPS和PTFE纤维质量比为50∶50时,制备的PPS+PTFE混纺针刺滤袋的整体使用寿命可达74个月。研究为燃煤电厂滤袋除尘器的超低排放及滤袋选型提供参考。

Cav3.2 channel regulates cerebral ischemia/reperfusion injury:a promising target for intervention

Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury.However,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear.Here,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons.The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons.We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury.Cav3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury.Additionally,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal apoptosis.In the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury.These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling.Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.

T_(2)* mapping MR成像评价脊髓缺血再灌注后铁死亡的机制研究

目的:通过7.0T T_(2)*mapping MR成像技术检测脊髓缺血再灌注(Spinal cord ischemia-reperfusion,SCIR)损伤后脊髓前角铁沉积变化,并分析其与铁死亡蛋白变化的关系,以此反映SCIR后铁死亡的作用机制。方法:选取48只Wistar大鼠(雄性,280~300 g),随机分为假手术组(n=8)和SCIR实验组(n=40)。实验组按缺血再灌注后不同恢复时间分为6 h组(n=8),12 h组(n=8),24 h组(n=8),48 h组(n=8)和72 h组(n=8)。建模完成后进行7.0T MR扫描。扫描后进行脊髓组织溶质载体家族11成员2(Solute carrier family 11 member 2,SLC11A2)、铁蛋白重链1(Ferritin heavy chain 1,FTH1)、谷胱甘肽过氧化物酶4(Glutathione peroxidase 4,GPX4)的免疫组化染色。采用方差分析、Tukey检验比较各组T_(2)*值和蛋白质表达水平的差异。结果:SCIR后6 h,脊髓前角T_(2)*值显著降低(P<0.001,Tukey检验),至24 h达到最低(P<0.001,Tukey检验),48 h组回升(P<0.001)。SCIR损伤后6 h,SLC11A2表达具有轻度增加趋势,FTH1表达显著降低(P=0.007,Tukey检验),SCIR损伤后24 h,SLC11A2、FTH1、GPX4表达均显著降低(P=0.031,P=0.009,P=0.004,Tukey检验)。结论:SCIR损伤后脊髓前角T_(2)*值、SLC11A2、FTH1、GPX4均出现一过性降低过程,且T_(2)*变化与GPX4蛋白变化一致,提示T_(2)*mapping可通过检测脊髓铁沉积的变化进一步反映铁死亡的作用机制。

Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.