Inhibitory Effects of Sodium Ferulate on Proliferation of Rabbit Aortic Smooth Muscle Cells Induced by Oxidized LDL

The effects of sodium ferulate(SF), a water-soluble element of Chinese medicine Angelica sinensis diels, on cell-mediated oxidative modification of human low density lipoprotein(LDL) and proliferation of rabbit aortic smooth muscle cells(SMCs) were investigated. Using experimental models of proliferation of cultured rabbit aortic SMCs induced by oxidized LDL(ox-LDL), the extent of oxidation was determined by thiobarbituric acid reactive substances(TBARS) method, MTT colorimetry and 3H-thymidine(3H-TdR) incorporation were used to observe proliferation of SMCs. It showed that SF effectively inhibited cell-mediated oxidation induced by Cu2+ in a concentration-dependent manner. At the final concentration of 40, 80, 120 gmL-1, SF could significantly inhibit 3H-TdR incorporation and cell Proliferation in a dose-dependent manner. The results indicated that SF could, in vitro protect LDL against oxidative modification and inhibit the proliferation of SMC, which might be due to its free radical scavenging capacity.

Effects of sodium ferulate on the ultrarapid delayed rectifier K^+ current in human atrial myocytes

Objective：To study the effects of sodium ferulate on the ultrarapid delayed rectifier K^＋ current（IKur） in human atrial myocytes. Methods：Human atrial myocytes were isolated by enzyme dispersion method. IKur, in human atrial myocytes were recorded by using the whole cell patch clamp. The changes of IKur were compared in the absence and the presence of sodium ferulate. Results：There was no effect of 0.4 g/L sodium ferulate on I-V relation of IKur. However, 0.4 g/L sodium ferulate inhibited IKur to some degrees at each test pulse. The current densities of IKur at ＋60 mV decreased from 4.997 ± 0.35 PA/PF to 3.331 ± 0.26 PA/PF（n = 6, P 〈 0.05）. The inhibitory effect was concentration-dependent. IC50 was（0.41 ±0.03）g/L and the Hill coefficient was 0.95 ± 0.05. Conclusion：Sodium ferulate as a potassium channel blocker can inhibit IKur in human atrial myocytes effectively.

Protective effect of sodium ferulate on cardiac hypertrophy in spontaneously hypertensive rats

OBJECTIVE To investigate the inhibitory effect and mechanism of sodium ferulate(SF)on myocardial hypertrophy in spontaneously hypertensive(SHR).METHODS Forty 14-week-old SHR male rats were randomly divided into model group(SHR,receive distilled water)and SF treatment groups(SF 20,40 and 80 mg·kg^-1 per day,respectively).Age-matched male Wistar-Kyoto(WKY)rats gavaged with distilled water served as controls.After 12 weeks of treatment,the effects of SF on cardiac hypertrophy were evaluated using echocardiographic measurement,pathological analysis and the expression of atrial natriuretic peptide(ANP),myosin heavy chainβ(β-MHC)-a gene related to myocardial hypertrophy.In order to explore the mechanism of SF on myocardial hypertrophy,the calcium-sensing receptor(CaSR),calcineurin(CaN),nuclear factor of activated T cell 3(NFAT3),phosphorylation NFAT3(p-NFAT3),zinc finger transcription factor(GATA4),phosphorylation GATA4(p-GATA4),protein kinase Cβ(PKC-β),Raf-1,extracellular regulated protein kinase 1/2(ERK 1/2),phosphorylation ERK1/2(p-ERK 1/2)and mitogen-activated protein kinase phosphatase-1(MKP-1)were detected.RESULTS The myocardial hypertrophy parameters,myocardial cell cross section area,left ventricular wall thickness and expression of ANP and β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 were significantly increased,while the left ventricular cavity was significantly smaller,expression of p-NFAT3 and MKP-1 were significantly decreased,meanwhile,the ultra⁃structure of cardiomyocytes was significantly damaged in 26-week-old SHR rats.Notably,SF significantly ameliorated myocardial hyper⁃trophy in 26-week-old SHR rats;suppressed the overexpression of ANP,β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 and increased the expression of p-NFAT3 and MKP-1.CONCLUSION SF can inhibit cardiac hypertrophy in SHR rats,and the mechanism may be related to the inhibition of CaSR mediated signaling pathway.

Neuroprotective Effects of Sodium Ferulate and Its Antidepressant-Like Effect Measured by Acute and Chronic Experimental Methods in Animal Models of Depression

Antidepressants with novel targets and without side effects are in great demand. Ferulic acid (FA) is a ubiquitous phenolic acid of low toxicity, and sodium ferulate (SF) is its sodium salt. Our previous studies have revealed that FA and SF show significant protective effect on excitotoxicity, we now test its potential neuroprotective and antidepressant-like effects. MTT assay and morphological analysis by fluorescence microscopy were adopted to measure the neuroprotective effects of SF;forced-swimming, tail-suspension, and chronic mild stress (CMS) tests were performed to assess its antidepressant-like activity. The results showed that SF had protection against H2O2-induced oxidative damage and dexamethasone (DXM)-induced neurotoxicity pheochromocytoma (PC12) cells. Acute administration of SF markedly decreased the duration of immobility during forced-swimming in rats and mice and tail-supension tests in mice. However, SF has no any effects on reserpine-induced hypothermia, 5-hydroxytryptophan-induced head-twitch response, and potentiation of noradrenaline toxicity in mice. Chronic administration of SF reversed the effects of CMS on consumption of food and sucrose solution, weight gain, and histopathology of hippocampus by light microscopy, and potently shortened the immobility time during forced-swimming test following CMS in rats. This study provides evidence that SF possesses obviously antidepressant-like activity, and the antidepressant-like effect may result from its neuroprotective effects.

Comparison of the effects of perinatal and neonatal administration of sodium ferulate on repair following excitotoxic neuronal damages induced by maternal oral administration of monosodium glutamate at a late stage of pregnancy

Objective: Our previous studies have revealed that ferulic acid (FA) and sodium ferulate (SF) show significant protective effect on excitotoxicity, the present study was conducted to compare its potential favorable effects of maternal,newborn,and both maternal and newborn intraperitoneal (ip) injection of SF on repair following excitotoxic neuronal damages induced by monosodium glutamate (MSG). Methods: The maternal mice were assigned randomly into seven groups (n = 10 animals in each group): control, 3SF, 20SF, 23SF, MSG, MSG + 3SF, MSG + 20SF, MSG + 23SF groups. The mice at 17 days of pregnancy were treated with or without MSG (2.0 g/kg body weight, ig, once) or/and SF (40 mg/kg body weight, ip), and their offerings treated with or without SF. And then their filial behaviors and hippocampal histopathology were studied. Results: The results showed that maternal, newborn, and both maternal and newborn administration of SF facilitated their filial brain repair, and attenuated the behavioral disorders and histopathological damages of their filial mice in MSG + 3SF, MSG + 20SF, and MSG + 23SF groups in varying degrees. However, the best effects were detected in the filial mice in MSG + 23SF group. Conclusion: Both maternal and newborn administration of SF is conducive to the filial neuronal repair following excitotoxic damages induced by glutamate.

Neurogenesis-enhancing effect of sodium ferulate and its role in repair following stress-induced neuronal damage

Ferulic acid (FA) is a ubiquitous phenolic acid of low toxicity, and sodium ferulate (SF) is its sodium salt. Our previous studies have revealed that FA shows neuroprotective effect and significant antidepressant- like effect. The aim of this study was to investigate its potential neurogenesis-enhancing effect and its role in repair following stress-induced neuronal damage. MTT assay was performed to measure the effect of SF on the growth of rat pheochromocytoma (PC12) cells;morphological and immunocytochemical meth- ods were used for assessing its differentiation-induc- ing action. Chronic mild stress (CMS) tests were per- formed to establish rat model of depression. The histopathology of animal brains was studied to ana- lyze CMS-induced morphological changes and the effect of SF on the repair of CMS-induced brain in- jury. The expressions of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and the proliferation of neural stem cell/neural progenitor cells were assessed in the hippocampi of chronic mild stress (CMS)-induced depression-like model rats by immunohistochemistry and bromodeoxyuridine (BrdU)- incorporation assays, respectively. Our in vitro tests showed that SF promoted the proliferation of PC12 cells in the concentration range of 5 - 320 μM, and induced PC12 cells to differentiate to more mature cells with the morphological characteristics and mo- lecular marker of neuronal-like cells. In vivo tests showed that SF up-regulated the expressions of NGF and BDNF, and induced the proliferation of neural stem cell/neural progenitor cells in the hippocampi of CMS-induced depression-like model rats. This study provides evidences that SF shows neurogenesis-en- hancing effect, and its antidepressant-like effect of SF may be related directly and closely to its above-men- tioned effect.

Effect of sodium ferulate on activation of postsynaptic density-95 after transient facol cerebral ischemia

It was confirmed that sodium ferulate (SF) could significantly improve neurologic function deficit, reduce cerebral infarct volume at 24 h after reperfusion, and weakened postsynaptic density-95 (PSD-95) activation in ische-mic area reacting to ischemia after transient middle cerebral artery occlusion ( MCAO) by Western immunoblot analy-

Protective effects of sodium ferulate in vascular endothelial function during cardiopulmonary bypass

Objective Cardiopulmonary bypass (CPB) and its related ischemia reperfusion injury may cause endothelial cell injury. To study the protective effects of sodium ferulate in vascular endothelial function during CPB by testing the changes of vascular endothelial cell(CEC) ,nitric oxide(NO) and endothelin-1 (ET-1) in children with congenital heart disease. Methods Sixty patients

Effect of sodium ferulate in combined with atorvastatin on the renal interstitial fibrosis and inflammatory cytokines in patients with diabetic nephropathy

Objective:To explore the effect of sodium ferulate in combined with atorvastatin on the renal interstitial fibrosis and inflammatory cytokines in patients with diabetic nephropathy (DN). Methods: A total of 111 patients with DN who were admitted in our hospital from January, 2016 to April, 2017 were included in the study and randomized into the observation group and the control 1 and 2 group with 37 cases in each group. The patients in the control group were given routine blood sugar reducing, blood pressure reducing, and high quality low protein diet. On the above basis, the patients in the control 2 group were orally administrated with atorvastatin before sleep (20 mg). On the basis of treatments in the control 1 group, the patients in the observation group were given sodium ferulate (0.3 g) + 0.9% NaCl (250 mL), ivdrip, 1 time/d, and administrated with atorvastatin before sleep (20 mg). The fasting peripheral venous blood before and after treatment in the three groups was collected. The glycse oxidase (GOD) method was used to detect FPG. ELISA was used to detect SCr, TGF-β, AngⅡ, CTGF, hs-CRP, TNF-α, and IL-6. RIA was used to detect BUN and 24hUAER. The strengthened chemiluminescence immunoassay was used to detect CⅣ and PCⅢ. MAP was recorded. Results: FPG, MAP, BUN, 24hUAER, and SCr after treatment in the control 2 group were significantly lower than those in the control 1 group. FPG, MAP, BUN, 24hUAER, and SCr after treatment in the observation group were significantly lower than those in the control 2 group. AngⅡ, TGF-β, CTGF, PCⅢ, and CⅣ after treatment in the control 2 group were significantly lower than those in the control 1 group. AngⅡ, TGF-β, CTGF, PCⅢ, and CⅣ after treatment in the observation group were significantly lower than those in the control 2 group. TNF-α, IL-6, and hs-CRP after treatments in the control 2 group were significantly lower than those in the control 1 group. TNF-α, IL-6, and hs-CRP after treatment in the observation group were significantly lower than those in the control 2 group.Conclusions:The sodium ferulate in combined with atorvastatin can effectively improve the renal function in patients with DN, alleviate the systemic inflammatory reaction, and delay the renal interstitial fibrosis speed.

Clinical value of sodium ferulate + Shenmai injection in the adjuvant treatment of acute myocardial infarction

Objective: To explore the clinical value of sodium ferulate + Shenmai injection in the adjuvant treatment of acute myocardial infarction (AMI). Methods: A total of 119 patients with AMI who were treated in our hospital between December 2014 and December 2017 were reviewed and divided into the control group (n=60) who received conventional western medicine +Shenmai injection therapy and the sodium ferulate group (n=59) who received conventional western medicine + sodium ferulate + Shenmai injection therapy. The differences in serum levels of myocardial injury markers, inflammatory mediators and ventricular remodeling-related indexes were compared between the two groups before treatment and after 2 weeks of treatment. Results: Before treatment, serum levels of myocardial injury markers, inflammatory mediators and ventricular remodeling-related indexes were not significantly different between the two groups. After 2 weeks of treatment, serum myocardial injury markers GMP-140, cTnT, MYO, NT-proBNP and H-FABP levels of sodium ferulate group were lower than those of control group;serum inflammatory mediators MCP-1, IL-18 and hs-CRP levels were lower than those of control group;serum ventricular remodeling-related indexes GDF-15, MMP-10 and CgA levels were lower than those of control group whereas IGF-1 level was higher than that of control group. Conclusion: Western medicine combined with sodium ferulate+ Shenmai injection therapy can effectively protect the myocardial function and inhibit the systemic inflammatory response and ventricular remodeling in patients with AMI.

Effect of sodium ferulate in combined with Huangqi injection on the coagulation and immunological function in patients with primary nephrotic syndrome

Objective:To explore the effect of sodium ferulate in combined with Huangqi injection on the coagulation and immunological function in patients with primary nephrotic syndrome (PNS).Methods: A total of 137 patients with PNS were included in the study and randomized into the observation group (n=69) and the control group (n=68). The patients in the treatment group were given routine treatment, anticoagulation, lipid regulation, and other symptomatic treatments. On this basis, the patients in the observation group were given sodium ferulate in combined with Huangqi injection. The coagulation, immunological function, and hemorrheology indicators before and after treatment in the two groups were compared.Results:Alb content after treatment in the two groups was significantly elevated when compared with before treatment (P<0.05), while ET, 24 h UPQ, Scr, and BUN levels were significantly reduced when compared with before treatment (P<0.05);moreover, the improvement degree of the above indicators in the observation group was significantly greater than that in the control group (P<0.05). PT and APTT after treatment in the two groups were significantly prolonged when compared with before treatment (P<0.05), while FIB, D-D content, whole blood high shear viscosity, low shear viscosity, blood viscosity, and ARBC were significantly reduced when compared with before treatment (P<0.05);moreover, the improvement degree of the above indicators in the observation group was significantly greater than that in the control group (P<0.05). CD3+, CD4+, and CD8+ after treatment in the two groups were significantly elevated when compared with before treatment (P<0.05). CD3+ and CD4+ after treatment in the observation group were significantly higher than those in the control group (P<0.05). CD4+/CD8+, IgG, and IgA after treatment in the observation group were significantly higher than those in the control group (P<0.05).Conclusions:Sodium ferulate in combined with Huangqi injection in the treatment of PNS can improve the coagulation function and hemorheology, alleviate the blood coagulation, enhance the immunological function, and recover the renal function.

阿魏酸钠治疗梅尼埃病模型小鼠的效果及机制研究

目的探讨阿魏酸钠治疗梅尼埃病(MD)模型小鼠的效果及机制。方法BALB/c小鼠采用后颅窝硬膜外入路内淋巴囊阻塞术联合腹腔注射醛固酮的方法构建MD模型,将造膜成功的60只小鼠随机分为模型组,阿魏酸钠低、中、高剂量组,地塞米松组,每组12只。另取12只BALB/c小鼠作为假手术组。分组鼓室给药后以听觉诱发脑干反应(ABR)检测各组小鼠听力水平。HE染色及磁共振成像(MRI)观测各组小鼠耳蜗形态及其膜迷路积水情况;酶联免疫吸附试验检测各组小鼠血清脂蛋白(a)[Lp(a)]及促炎因子白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平;免疫组织化学染色及Western blot法检测各组小鼠Lp(a)表达。结果与假手术组比较,模型组小鼠ABR阈值、膜迷路积水评分、中阶面积占比、血清Lp(a)、IL-6与TNF-α水平、耳蜗组织Lp(a)阳性表达的IOD值与Lp(a)蛋白表达增加(P<0.05);与模型组比较,阿魏酸钠低、中、高剂量组及地塞米松组小鼠ABR阈值、膜迷路积水评分、中阶面积占比、血清Lp(a)、IL-6与TNF-α水平、耳蜗组织Lp(a)阳性表达的IOD值与Lp(a)蛋白表达降低(P<0.05),且高剂量阿魏酸钠效果更明显。结论阿魏酸钠可下调Lp(a)蛋白表达,减少促炎因子产生,抑制炎症反应,进而减轻MD小鼠膜迷路积水症状,并改善其听觉功能。

舒血宁联合奥扎格雷钠注射液对脑梗死患者血清SF、CRP及HIF-1α的影响

目的探讨舒血宁联合奥扎格雷钠注射液对脑梗死患者血清铁蛋白(serum ferritin,SF)、C反应蛋白(C-reactive protein,CRP)及缺氧诱导因子-1α(hypoxia-inducible factor 1α,HIF-1α)水平的影响。方法选取经CT或MRI证实的60例脑梗死患者,依据随机数字表法分成2组,每组30例。对照组予奥扎格雷钠治疗,联合组在对照组基础上予舒血宁注射液治疗,7天1个疗程,治疗2个疗程。检测治疗前后血清SF、CRP及HIF-1α水平,观察其临床疗效及安全性。结果与治疗前比,治疗后2组SF、CRP及HIF-1α水平均降低(P<0.05),NIHSS评分、血小板活性指标均降低(P<0.05);与对照组相比,联合组SF、CRP及HIF-1α水平均较低(P<0.05),NIHSS评分、血小板活性指标均较低(P<0.05),临床疗效较高(P<0.01)。结论舒血宁联合奥扎格雷钠注射液对脑梗死有较好的疗效,抑制血小板聚集,有效降低血清铁蛋白、CRP及HIF-1α水平。

基于硼氢化钠原位还原的纳米金杂化酶的制备及催化阿魏酸甘油酯合成

建立了一种基于硼氢化钠原位还原法制备纳米金杂化酶用以合成阿魏酸甘油酯的方法,使杂化酶的催化活性、稳定性及结构的刚性皆有所提高.利用硼氢化钠原位还原法制备了NaBH_(4)@AuNPs-CRL杂化酶,通过单因素实验得到了最优的杂化条件,并利用荧光光谱、红外光谱、X-射线电子能谱、透射电镜等方法探究了杂化前后酶结构的变化.研究表明制备的NaBH_(4)@AuNPs-CRL杂化酶蛋白二级结构中α-螺旋含量减少、β-折叠含量增加,杂化酶比活性为4.91±0.12 U∙mg^(-1),与游离酶相比提高了66.44%,最佳条件下催化合成阿魏酸甘油酯的转化率为98.39%±3.65%,批式操作稳定性实验表明杂化酶的稳定性有较大提升.

酚酸-透明质酸钠接枝物的制备及体外抗氧化研究

目的以透明质酸钠(sodium hyaluronate,HA)为研究对象,利用酚酸对其修饰改性以期获得抗氧化活性更好甚至新活性的分子结构。方法采用自由基介导的接枝方法制备5种不同的酚酸-透明质酸钠接枝物,选出接枝度最高的接枝物进行合成条件优化。通过红外光谱(infrared spectroscopy,IR)、紫外光谱(ultraviolet spectrum,UV)、核磁共振氢谱(^(1)H NMR spectroscopy,^(1)H NMR)、场发射扫描电镜(field emission scanning electron microscopy,FESEM)、热重分析法(thermogravimetry analysis,TGA)对接枝物进行表征,通过测定接枝物对1,1-二苯基-2-三硝基苯肼(DPPH·)、2,2-联氮-二(3-乙基-苯并噻唑-6-磺酸)二铵盐(ABTS^(+)·)及超氧阴离子自由基(O^(2-)·)清除能力反应出接枝物的体外抗氧化能力。结果在相同条件下,5种酚酸-透明质酸钠接枝物种中接枝度最高的是阿魏酸-透明质酸钠接枝物(ferulic acid-sodium hyaluronate FA-HA),对FA-HA合成条件行进优化,得到最高的接枝度为(16.59±0.31)mg/g。通过IR、UV、^(1)H NMR、FESEM、TGA验证了接枝物的形成,推测可能形成了酯键。分子质量检测结果表明,通过本方法得到的接枝物的分子质量有小幅下降但分子分布均一性提高,平均分子质量为31.5 ku。FESEM结果显示,接枝物呈现紧密相连的片状结构,表面相对光滑。热重分析(TGA)结果表明,接枝物的热稳定性降低。体外抗氧化实验结果表明,在0.25~10 g/L浓度范围内,FA-HA对DPPH·、ABTS^(+)·和O^(2-)·的最大清除率分别为(83.76±4.86)%、(76.95±5.06)%和(83.08±2.51)%,高于原HA及FA。结论自由基接枝法成功将FA与HA接枝在一起,且接枝后的FA-HA具有更好的体外抗氧化活性,为酚酸-HA接枝物的深入研究和开发应用提供了理论依据。

阿魏酸钠通过SIRT1/FOXO3A改善血管性痴呆大鼠学习记忆障碍的机制研究

目的探究阿魏酸钠在血管性痴呆(vascular dementia,VD)大鼠中的神经保护作用及其对前额叶皮质沉默信息调节因子1(silent information regulator 1,SRIT1)和叉头框转录因子O3A(forkhead box transcription factor O3A,FOXO3A)表达的影响。方法将32只雄性SD大鼠随机分成4组,每组8只。模型组和阿魏酸钠组大鼠行双侧颈总动脉栓塞;假手术组进行相同的手术操作,但不做结扎处理;正常组不做处理。阿魏酸钠组连续4周灌胃阿魏酸钠溶液(100 mg/kg),其余3组接受相同体积的生理盐水灌胃。通过Morris水迷宫、尼氏染色、Western Blot和免疫组织化学染色法观察比较各组大鼠行为学、细胞形态及SIRT1和FOXO3A蛋白的表达情况。结果正常组和假手术组神经元呈现较完整的形态结构。相较于正常组,模型组大鼠逃避潜伏期显著延长、穿越平台次数明显减少(P<0.05),细胞核固缩,SIRT1表达水平显著下降(P<0.05),FOXO3A表达显著上升(P<0.05);与模型组相比,阿魏酸钠组细胞形态得以改善,逃避潜伏期和FOXO3A蛋白表达均降低(P<0.05),穿台次数和SIRT1蛋白表达水平均升高(P<0.05)。结论阿魏酸钠通过调节SIRT1/FOXO3A改善大鼠学习记忆能力,为VD治疗提供了一定的研究基础。

川芎治疗偏头痛药理机制研究进展

偏头痛在中国是一种常见的搏动性、原发性的头痛病,多一侧起病,重者可致残,对患者的生活质量产生重大影响,是目前治疗的一大难点。中医治疗偏头痛既可以改善疾病的症状,还可以祛除疾病的根源,具有多目标、多途径的特点。通过对治疗偏头痛的古今医案数据进行分析,发现中医治疗主要采取祛瘀、平肝阳、补虚三种治疗策略。其中化瘀方中大多含有川芎,发现川芎可以活血化瘀,改善血液流变学性质,镇静,镇痛,清除氧自由基,同时也发现含有川芎的药对居于偏头痛治疗使用药对之首。川芎是临床上治疗头痛、血管性头痛、偏头痛用药频率最高的单味中药之一。该文对川芎治疗偏头痛的药理作用机制进行综述,为川芎临床治疗和预防偏头痛提供理论科学依据。并对川芎的有效成分现代研究进行归纳梳理。结果发现川芎治疗偏头痛的药理机制包括抑制氧自由基活性,减轻炎症反应;抗神经元凋亡,保护脑神经;调节神经递质,降低痛阈值;抗血小板聚集;调肠道菌群等。

阿魏酸钠通过miR-216b-3p/Nrf2通路减轻缺氧缺血胚胎大鼠氧化应激反应

目的:探究阿魏酸钠(SF)通过miR-216b-3p/Nrf2通路对缺氧缺血性脑病(HIE)胚胎大鼠大脑的干预作用以及减轻氧化应激损伤的作用机制。方法:将成年雌性SD大鼠和雄鼠,按照3∶1比例合笼获得怀孕的雌鼠。然后将孕鼠分为假手术组(sham)、缺氧缺血性脑病模型组(HIE)、SF低剂量组(HIE+SF-L)和SF高剂量组(HIE+SF-H)。通过无创止血钳夹闭子宫两侧动脉和卵巢血管法制备胚胎大鼠HIE模型。SF治疗组腹膜腔注射SF。采用HE染色观察胚胎大鼠大脑皮质的病理变化;免疫荧光观察核因子红细胞系2相关因子2(Nrf2)、过氧化还原酶1(PRDX1)的表达情况;Western Blot检测胚胎大鼠脑组织中Nrf2和PRDX1蛋白的表达;real time RT-PCR检测miR-216b-3p的表达以及Nrf2和PRDX1的mRNA表达;WST-8法和TBA法检测脑组织中的超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果:与sham组对比,HIE组胚胎大鼠的大脑损伤加重,病理改变明显;HIE组中Nrf2蛋白表达和mRNA水平降低(P<0.05),PRDX1的蛋白水平和mRNA水平显著上调(P<0.05),miR-216b-3p表达水平显著升高(P<0.05);并且Nrf2的平均荧光强度显著降低(P<0.05),PRDX1的平均荧光强度显著增加(P<0.05);SOD活性显著下调,MDA含量显著增加(P<0.05)。与HIE组对比,各剂量SF组的大脑皮质病理结构明显改善,脑损伤减轻;Nrf2和PRDX1的蛋白表达、mRNA水平以及平均荧光强度均显著上升(P<0.05);miR-216b-3p表达水平均显著下调,以SF高剂量组下调最为显著(P<0.05);并且SOD活性显著上调,MDA含量显著下调(P<0.05)。结论:SF通过miR-216b-3p/Nrf2信号通路在HIE的发生发展过程中发挥重要作用,并减轻胚胎大鼠受到的氧化应激损伤。

基于c-Jun氨基末端激酶/p38丝裂原活化蛋白激酶信号通路探讨阿魏酸钠对偏头痛大鼠炎症反应的抑制作用

目的 探讨阿魏酸钠(SF)通过调控JNK/p38 MAPK信号通路对偏头痛大鼠炎症反应的抑制作用。方法 腹腔注射硝酸甘油制备偏头痛大鼠模型,模型制作成功后随机分为模型组、SF低剂量(SF-L)组(50 mg/kg)、 SF高剂量(SF-H)组(100 mg/kg)、SF+JNK抑制剂(SF+SP600125)组(SF 100 mg/kg+SP600125 10 mg/kg)、 SF+JNK激活剂[SF+茴香霉素(AN)]组(SF 100 mg/kg+AN 5 mg/kg),每组12只,另取12只SD大鼠不做处理作为空白组。给药结束24 h后观察各组大鼠行为学变化,ELISA法检测血清中5-羟色胺(5-HT)、一氧化氮(NO)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)水平,TUNEL染色观察脑组织神经元凋亡情况,免疫组织化学法检测脑组织中TNF-α、 IL-6、降钙素基因相关肽(CGRP)表达,Western blotting法检测脑组织中JNK/p38 MAPK通路相关蛋白的表达。结果 与空白组比较,模型组大鼠挠头次数以及爬笼次数明显增加,神经元凋亡率显著升高;血清5-HT含量显著降低,NO、TNF-α和IL-6水平显著升高;脑组织中TNF-α、IL-6和CGRP表达以及磷酸化JNK(p-JNK)/JNK、磷酸化p38 MAPK(p-p38 MAPK)/p38 MAPK比值均显著升高(均P<0.05)。与模型组比较,SF-L组、SF-H组大鼠挠头次数及爬笼次数显著减少,神经元凋亡率显著降低;血清中5-HT含量显著升高,NO、TNF-α和IL-6水平显著降低;脑组织中TNF-α、IL-6和CGRP表达以及p-JNK/JNK、p-p38 MAPK/p38 MAPK比值均显著降低(均P<0.05)。与SF-H组比较,SF+SP600125组能够显著增强SF对偏头痛大鼠的保护作用;SF+AN组能够显著逆转SF对偏头痛大鼠的保护作用。结论 SF可能通过抑制JNK/p38 MAPK信号通路的表达,有效抑制偏头痛大鼠神经源性炎症反应,减少神经元凋亡,实现对偏头痛大鼠的保护作用。

阿魏酸钠经RhoA和Rho-kinase信号通路抑制小鼠肝纤维化的机制研究

目的:探讨阿魏酸钠对于四氯化碳诱导的小鼠肝纤维化的抑制机制。方法:将CL级昆明属小鼠随机分为正常对照组、CCl4-花生油模型组(模型组)、阿魏酸钠给药组(给药组),每组20只。模型组小鼠和给药组小鼠分别给予CCl4-花生油(1∶1,V/V)1ml/kg灌胃,正常对照组小鼠给予同等剂量生理盐水,三组均为1次/d,连续8周;从第9周开始,给药组小鼠给予阿魏酸钠20mg/kg灌胃,1次/d,连续给药4周。12周后,检测各组小鼠肝功能水平、肝影像学指标、病理变化及肝脏中RhoA、Rho-kinase的总体情况。结果:通过正常对照组、模型组及给药组的小鼠肝功能和肝纤维化指标等指标对比,发现阿魏酸钠能显著抑制小鼠肝纤维化程度。结论:阿魏酸钠可能通过调节RhoA和Rho-kinase信号通路抑制小鼠肝纤维化。