Imidazolines促胰岛素分泌作用机制的研究

目的观察ｉｍｉｄａｚｏｌｉｎｅｓ：ｐｈｅｎｔｏｌａｍｉｎｅ，ｅｆａｒｏｘａｎ和ｉｄａｚｏｘａｎ对ＡＴＰ调节的钾离子通道的影响，从而探讨其促胰岛素分泌的作用机制。方法用“内面向外”的膜片钳制技术，在培养的无性系的ＲＩＮｍ５Ｆ胰岛素分泌细胞进行实验。结果ｐｈｅｎｔｏｌａｍｉｎｅ５０μｍｏｌ·Ｌ－１明显抑制ＡＴＰ调节的钾离子通道，显著降低通道开放的概率。Ｅｆａｒｏｘａｎ５０μｍｏｌ·Ｌ－１明显降低通道开放的概率，抑制钾离子通道的开放，但作用维持时间短。ｉｄａｚｏｘａｎ５０μｍｏｌ·Ｌ－１对通道开放概率的影响不明显。结论ｐｈｅｎｔｏｌａｍｉｎｅ，ｅｆａｒｏｘａｎ和ｉｄａｚｏｘａｎ促胰岛素分泌的作用与阻断ＡＴＰ调节的钾离子通道有关。

Neuroprotective effects of receptor imidazoline 2 and its endogenous ligand agmatine

Receptor imidazoline 2 （I2） is one of the imidazoline receptors with high affinity for [^3H]-idazoxan. Receptor I2, being classified into I2A and I28 subtypes, is mainly localized to the outer membrane of mitochondria in liver, kidney and brain. Receptor I2, displaying high similarity of sequence with monoamine oxidase-B （MAO-B）, is structurally related to MAO-B, but the I2 imidazoline binding site （IEBS） with ligand is distinct from the catalytic site of MAO-B. Agmatine is the endogenous ligand of receptor I2. Accumulating evidence have revealed that the activation of receptors I2 may produce neuroprotective effects by increasing expression of glial fibriUary acidic protein （GFAP） in astrocytes, inhibiting activity of MAO, reducing calcium overload in cells. Agmatine exerts neuroprotection against ischemia-hypoxia, injury, glutamateinduced neurotoxicity by activating imidazoline receptors, blocking N-methyl-D-aspartate （NMDA） receptor, inhibiting all isoforms of nitric oxide synthase （NOS）, and selectively blocking the voltage-gated calcium channels （VGCC）. It would be expected that agmatine is one of the potential neuroprotective agents.

Corrosion Inhibition of Imidazoline Derivates with Benzene Rings on Mild Steel in CO_2-Saturated Brine Solution

Corrosion inhibition of three imidazoline derivates with different numbers of benzene rings,namely 2-phenyl-1-ethylamino imidazoline（CI-1）,2-phenyl-1-ethylamino-1-methylbenzyl quaternary imidazoline（CI-12） and 2-phenyl-1-benzoyl ethylamino imidazoline（CI-13）,on mild steel in CO2-saturated brine solution was evaluated by mass-loss method and potentiodynamic polarization method.The results show that the three imidazoline derivates can inhibit CO2 corrosion effectively with CI-12 ranking the highest.They mainly restrain the anodic dissolution and act as anodic-type inhibitors.The adsorptions of these derivates on the mild steel surface follow the Langmuir adsorption isothermal equation and belong to chemical adsorption.

Hydroxy- and Aminoethyl Imidazolines of Cottonseed Oil Fatty Acids as Additives for Diesel Fuels

In the research, aminoethyl imidazolines of cottonseed oil fatty acids with diethylenetriamine have been synthesized using the ultrasonic device creating the effect of cavitation. The yield of imidazolines was 90% - 95%. The influence of the synthesized imidazolines on lubricity quality of low sulfur diesel fuels having low lubricating quality was studied. The results showed that at concentrations 200 - 250 ppm the synthesized imidazolines can be applied as additives enhancing lubricity quality of diesel fuels.

Comparative effects of idazoxan, efaroxan, and BU 224 on insulin secretion in the rabbit: Not only interaction with pancreatic imidazoline I2 binding sites

The nature of the binding site(s) involved in the insulin secretory activity of imidazoline compo- unds remains unclear. An imidazoline I2 binding site (I2BS) has been neglected since the classic I2 ligand, idazoxan, does not release insulin. Using the rabbit as an appropriate model for the study of this type of binding sites, we have tried to re-evaluate the effects of idazoxan, the selective I2 compound BU 224, and efaroxan on insulin secretion. Mimicking efaroxan, idazoxan and BU 224 potentiated insulin release from perifused islets in the presence of 8 mM glucose. In static incubation, insulin secretion induced by idazoxan and BU 224 exhibited both dose and glucose dependencies. ATP-sensitive K+ (KATP) channel blockade, though at a different site from the SUR1 receptor, with subsequent Ca2+ entry, mediates the insulin releasing effect of the three ligands. However, additional MAO independent intracellular steps in stimulus- secretion coupling linked to PKA and PKC activation are only involved in the effect of BU 224. Therefore, both an I2 related binding site at the channel level shared by the three ligands and a putative I3-intracellularly located binding site stimulated by BU 224 would be mediating insulin release by these compounds. In vivo experiments reassess the abilities of idazoxan and BU 224 to enhance glucose-induced insulin secretion and to elicit a modest blood glucose lowering response.

2-(2-Benzofuranyl)-2-imidazoline treatment within 5 hours after cerebral ischemia/reperfusion protects the brain

We previously demonstrated that administering 2-（2-benzofuranyl）-2-imidazolin（2-BFI）, an imidazoline I2 receptor agonist, immediately after ischemia onset can protect the brain from ischemic insult. However, immediate administration after stroke is difficult to realize in the clinic. Thus, the therapeutic time window of 2-BFI should be determined. Sprague-Dawley rats provided by Wenzhou Medical University in China received right middle cerebral artery occlusion for 120 minutes, and were treated with 2-BFI（3 mg/kg） through the caudal vein at 0, 1, 3, 5, 7, and 9 hours after reperfusion. Neurological function was assessed using the Longa＇s method. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride assay. Morphological changes in the cortical penumbra were observed by hematoxylin-eosin staining under transmission electron microscopy. The apoptosis levels in the ipsilateral cortex were examined with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling（TUNEL） assay. The protein expression of Bcl-2 and BAX was detected using immunohistochemistry. We found the following： Treatment with 2-BFI within 5 hours after reperfusion obviously improved neurological function. Administering 2-BFI within 9 hours after ischemia/reperfusion decreased infarct volume and alleviated apoptosis. 2-BFI administration at different time points after reperfusion alleviated the pathological damage of the ischemic penumbra and reduced the number of apoptotic neurons, but the protective effect was more obvious when administered within 5 hours. Administration of 2-BFI within 5 hours after reperfusion remarkably increased Bcl-2 expression and decreased BAX expression. To conclude, 2-BFI shows potent neuroprotective effects when administered within 5 hours after reperfusion, seemingly by up-regulating Bcl-2 and down-regulating BAX expression. The time window provided clinical potential for ischemic stroke by 2-BFI.

Increased monoamine oxidase activity and imidazoline binding sites in insulin-resistant adipocytes from obese Zucker rats

BACKGROUND Despite overt insulin resistance,adipocytes of genetically obese Zucker rats accumulate the excess of calorie intake in the form of lipids.AIM To investigate whether factors can replace or reinforce insulin lipogenic action by exploring glucose uptake activation by hydrogen peroxide,since it is produced by monoamine oxidase(MAO)and semicarbazide-sensitive amine oxidase(SSAO)in adipocytes.METHODS 3H-2-deoxyglucose uptake(2-DG)was determined in adipocytes from obese and lean rats in response to insulin or MAO and SSAO substrates such as tyramine and benzylamine.14C-tyramine oxidation and binding of imidazolinic radioligands[3H-Idazoxan,3H-(2-benzofuranyl)-2-imidazoline]were studied in adipocytes,the liver,and muscle.The influence of in vivo administration of tyramine+vanadium on glucose handling was assessed in lean and obese rats.RESULTS 2-DG uptake and lipogenesis stimulation by insulin were dampened in adipocytes from obese rats,when compared to their lean littermates.Tyramine and benzylamine activation of hexose uptake was vanadate-dependent and was also limited,while MAO was increased and SSAO decreased.These changes were adipocyte-specific and accompanied by a greater number of imidazoline I2 binding sites in the obese rat,when compared to the lean.In vitro,tyramine precluded the binding to I2 sites,while in vivo,its administration together with vanadium lowered fasting plasma levels of glucose and triacylglycerols in obese CONCLUSION The adipocytes from obese Zucker rats exhibit increased MAO activity and imidazoline binding site number.However,probably as a consequence of SSAO down-regulation,the glucose transport stimulation by tyramine is decreased as much as that of insulin in these insulin-resistant adipocytes.The adipocyte amine oxidases deserve more studies with respect to their putative contribution to the management of glucose and lipid handling.

Imidazolines对RINm5F胰岛素分泌细胞钾离子通道的作用

Ｉｍｉｄａｚｏｌｉｎｅｓ对ＲＩＮｍ５Ｆ胰岛素分泌细胞钾离子通道的作用梁日欣（药理教研室）刘晓光（附属第一医院）近年来的实验研究已经证明α２－肾上腺素受体阻断剂Ｉｍｉｄａｚｏｌｉｎｅｓ如：ｐｂｅｎｔｏｌａｍｉｎｅ［１］，Ｅｆａｒｏｘａｎ和Ｉｄａｚｏｘａ...

Vibrational and Electronic Spectra of 2-Phenyl-2-Imidazoline: A Combined Experimental and Theoretical Study

The structural properties and vibrational frequencies of 2-phenyl-2-imidazoline have been investigated using theoretical and techniques by which a good correlation was observed. The assignments of the vibrational modes were performed with the help of normal co-ordinate analysis following the Scaled Quantum Mechanical Force Field methodology. Natural bond orbital analysis and the highest occupied molecular orbital-lowest unoccupied molecular orbital gap analysis have been carried out. UV-visible spectrum of the compound was recorded and compared with the theoretical UV-visible spectrum of the title molecule using Symmetry Adapted Cluster-Configuration Interaction method which yielded good agreement. Our results reflect that the title compound can be used as good source of UV light.

New Facile Synthesis of 2-Aryloxy-5-(2-furfurylidene)- 4H-imidazolin-4-ones

Novel 2-aryloxy-5-(2-furfurylidene)-4H-imidazolin-4-ones 6 were synthesized by aza-Wittig reaction of vinyliminophosphorane 4 with phenyl isocyanate and subsequent condensation with Various substituted phenols in the presence of catalytic amount of potassium carbonate. The products are confirmed by H-1 NMR, MS, IR and elementary analysis.

Synthesis of Arylsubstituted Imidazolin-2-one Analogues

Herein we reported a one-pot synthesis of arylsubstituted imidazolin-2-ones by the cyclization of α-aminoacetophenone hydrochloride analogues 2 with arylisocyanates 3. Compared with other known synthetic route, this method resulted in higher yield.

水溶性咪唑啉酰胺的合成及其性能研究

按照四乙烯五胺∶壬酸∶冰乙酸的摩尔比为1∶1∶4.5进行反应物料配制,以甲苯为携水剂,通过端基酰胺化脱水反应、乙酰胺化脱水反应和环化脱水反应,最终制备合成了水溶性咪唑啉酰胺。依据国标方法对水溶性咪唑啉酰胺在不同质量分数下进行水溶性测试研究。结果表明,制备合成的水溶性咪唑啉酰胺具有良好的水溶性。利用GaussView 6可视化软件对水溶性咪唑啉酰胺分子进行结构优化,获得了最高占据分子轨道HOMO和最低未占分子轨道LUMO能量分布图,通过Gaussian 16软件的量化模拟计算分析,得到了最高占据轨道能量(E_(HOMO))和最低未占轨道能量(E_(LUMO)),根据前线轨道理论,揭示了水溶性咪唑啉酰胺的缓蚀性能。同时,利用失重法对水溶性咪唑啉酰胺的缓蚀性能进行研究,并根据扫描电镜(SEM)形貌分析,进一步证明了合成的水溶性咪唑啉酰胺具有良好的缓蚀效果。

富含双键咪唑啉在饱和CO_(2)盐水中缓蚀行为研究

目的合成含有两个双键的亚油酸咪唑啉,与传统的含有单个双键油酸咪唑啉对比,研究其结构对其缓蚀性能的影响。方法在60℃下将Q235钢浸泡于饱和CO_(2)的3%(w)NaCl溶液中,通过失重、电化学测试和缓蚀效率测试,并通过表面分析方法观察腐蚀后钢片形貌变化,最后通过理论计算对合成缓蚀剂进行性能研究。结果电化学与失重结果显示在加入质量浓度为200 mg/L的亚油酸咪唑啉后,缓蚀效率能达到90%,缓蚀性能优于常见的油酸咪唑啉。在结构上,由于亚油酸咪唑啉分子比油酸咪唑啉多了一个双键,增加了咪唑啉缓蚀剂的吸附位点,使其能更好地吸附于金属的表面。结论亚油酸咪唑啉对碳钢有很好的缓蚀性能;在同等实验条件下,缓蚀性能优于油酸咪唑啉;其吸附满足Langmuir吸附等温线;吸附过程中主要通过N—Fe键吸附在Fe表面。

不同脱水剂和催化剂对油酸基咪唑啉缓蚀性能的影响

选用二甲苯、活性氧化铝和硼酸等作为脱水剂或催化剂,分别合成了三种油酸基咪唑啉,利用红外光谱对咪唑啉的结构进行了表征,使用质量损失法、极化曲线法和交流阻抗法等技术比较了三种油酸基咪唑啉缓蚀剂在H_(2)S/CO_(2)饱和的高矿化度溶液中对碳钢的缓蚀性能。结果表明,使用活性氧化铝催化合成的咪唑啉缓蚀效果最好。

咪唑啉季铵盐缓蚀剂改性蒙脱土/水性环氧纳米复合涂料

以油酸、二乙烯三胺和氯化苄为原料,合成了油酸基咪唑啉季铵盐缓蚀剂。通过FTIR、^(1)HNMR对其结构进行了表征,并离子交换至钠基蒙脱土(DK0)层间,制备了缓蚀剂改性蒙脱土(QACDK0)。通过XRD、TGA和UV-Vis对其结构、组成及层间缓蚀剂释放性能进行了表征。结果表明,咪唑啉季铵盐缓蚀剂约占QACDK0质量的38.96%,并将蒙脱土层间距由1.28 nm(DK0)扩大至3.98 nm(QACDK0)。利用DLS及Zeta电位对添加有QACDK0的水性环氧树脂进行了稳定性测试,其Zeta电位为–27.8 mV,具有较高的稳定性。电化学阻抗谱(EIS)测试表明,在腐蚀介质中浸泡30 d后,基于QACDK0制备的清漆漆膜仍具有2.29×10^(8)Ω·cm^(2)的高阻抗,表明涂层具有较好的耐腐蚀性。并且在耐中性盐雾测试中,QACDK0对应的防腐色漆耐盐雾时间最长,验证了该涂层具有良好的耐盐雾性能。

基于机器学习的CO_(2)-咪唑啉体系腐蚀速率预测模型研究

针对以往缓蚀剂性能预测模型缺乏对CO_(2)腐蚀环境的考虑,以CO_(2)环境参数和咪唑啉类缓蚀剂相关参数作为输入特征,通过数据搜集、数据补全、特征筛选构建数据集,对比KNN、SVR、RF、GBDT算法的预测模型。结果表明考虑环境参数的缓蚀性能预测模型是可行的,四种模型的R2均大于0.9,其中GBDT模型预测效果最好,R2为0.957,MRE为20.9%;SVR模型预测效果最差,R2为0.922,MRE为83.3%。

核电厂闭式冷却水系统中烯基胺乙基咪唑啉的缓蚀性能

采用浸泡腐蚀试验、电化学测试和表面分析等方法,在模拟核电站闭式冷却水(CCW)系统工况下,研究了烯基胺乙基咪唑啉(IM)缓蚀剂对CCW系统关键材料20G碳钢的缓蚀效果,分析了其缓蚀机理,并通过热重分析考察了IM在CCW系统环境中的热稳定性。结果表明:当IM质量分数为30 mg/kg时,其对20G碳钢的缓蚀率就可达到99%以上;在除盐水中添加60 mg/kg IM就可与添加75 mg/kg磷酸钠起到相同的缓蚀效果(缓蚀率99.9%以上);随着IM含量增加,20G碳钢的自腐蚀电位正移,腐蚀电流密度减小;IM分子在240℃左右开始发生分解,到500℃基本分解完成。IM为阳极型缓蚀剂,通过吸附在20G碳钢表面形成保护膜缓解其腐蚀。

咪唑啉与碘化钾对钢在醋酸中的缓蚀协同效应

采用失重法、动电位极化曲线法、电化学阻抗图谱(EIS)及扫描电子显微镜(SEM)研究了咪唑啉(IM)与碘化钾(KI)对冷轧钢在1.0 mol·L^(-1)醋酸(CH_(3)COOH)介质中的缓蚀协同效应。结果表明,单独咪唑啉对冷轧钢有良好缓蚀效果,缓蚀率随温度和咪唑啉浓度的升高而增大,50℃时最高可达到82%;加入KI复配后,缓蚀效果提高,50℃时达到了90.1%;且缓蚀协同效应系数大于1,两者存在缓蚀协同效应。IM与KI复配前后在钢表面的吸附规律均符合Langmuir吸附等温式,IM/KI复配后吸附平衡常数(K)进一步增大,而标准吸附Gibbs自由能(ΔG^(e))进一步变负。IM、KI、IM/KI均为以阴极抑制为主的混合型缓蚀剂,且IM/KI复配后腐蚀电流密度较复配前明显减小;Nyquist图谱主要包含高频区的容抗弧和低频区的感抗弧,IM与KI复配后电荷转移电阻增加。SEM微观形貌分析得出,IM与KI复配后更为有效地降低了醋酸对钢表面的侵蚀。

不同碳链长度对称双咪唑啉缓蚀剂的合成与性能研究

以月桂酸、肉豆蔻酸、棕榈酸、硬脂酸和四乙烯五胺为主要原料,反应条件为原料摩尔比1∶1.2,经酰胺化4 h,酰胺化温度150℃,环化4 h,环化温度190℃;后加入氯化苄进行材料改性,反应条件为摩尔比1∶1.2,反应时间10 h,反应温度80℃,得到烷基碳链长度分别为C11(LIRQ)、C13(MIRQ)、C15(MIRQ)、C17(PIRQ)的双对称咪唑啉缓蚀剂。采用红外光谱对其官能团结构进行表征,采用静态失重法和电化学极化曲线法,并通过透射电镜观察试片表面形貌,探究烷基链长度对缓蚀性能的影响。失重实验和极化曲线结果表明,在1 mol/L HCl介质中,随着烷基链长度增加,缓蚀剂浓度和实验温度提高其缓蚀率逐渐增加。

月桂酸咪唑啉对铜在盐酸溶液中缓蚀行为研究

通过电化学方法中动电位极化曲线和电化学阻抗谱研究月桂酸咪唑啉在0.5 mol/L盐酸中对铜的缓蚀行为,采用量子化学计算(Gaussian)、分子动力学模拟(MD)的方法探究月桂酸咪唑啉的缓蚀机理。研究结果表明:0.1 mmol/L月桂酸咪唑啉对0.5 mol/L盐酸中铜的缓蚀效率最高,为96.58%,增大浓度反而会降低缓蚀效率;月桂酸咪唑啉以物理吸附和化学吸附两者结合的方式形成吸附膜,吸附膜相对致密,其中咪唑啉环呈现平行吸附的特点。