表柔比星与人血白蛋白的相互作用特点

目的研究表柔比星与人血清白蛋白的相互作用特点。方法用荧光猝灭光谱及同步荧光光谱技术测定在不同温度下表柔比星对人血清白蛋白荧光的猝灭规律。结果表柔比星对人血清白蛋白荧光呈规律性猝灭,17℃时的n为1.113,K为5.87×10~4,37℃时的n为1.128,K为6.85×10~4。表柔比星使白蛋白的同步光谱中最大发射峰红移。结论表柔比星与人血清白蛋白只有1个结合位点,表现为疏水作用,两者结合使白蛋白的极性略有增加。     

荧光光谱法研究Ca2+存在下左氧氟沙星与人血清白蛋白的结合作用

目的：研究左氧氟沙星对人血清白蛋白以及在ca^2＋存在下左氧氟沙星与人血清白蛋白的结合作用。方法：通过荧光光谱法分析了左氧氟沙星对人血清白蛋白以及ca^2＋存在条件下左氧氟沙星对人血清白蛋白荧光淬灭光谱、同步荧光光谱,根据热力学方程讨论两者间主要的作用力类型。结果：在生理条件（pH=7．4,37℃）下,根据Stem—Volmer方程和荧光淬灭双倒数图,确定了左氧氟沙星对人血清白蛋白淬灭类型为静态淬灭,左氧氟沙星对人血清白蛋白的结合常数K=1．46×10^5L·mol^-1,结合位点n=1．1,根据热力学方法确定作用力类型为疏水作用力;在ca^2＋存在条件下,淬灭类型和作用力类型不变,结合常数K=2．38×10^4L·mol^-1,结合位点n：1．02。结论：在ca^2＋存在条件下,左氧氟沙星对人血清白蛋白的荧光淬灭减弱,结合常数和结合位点均变小。为研究左氧氟沙星的生物学效应,以及左氧氟沙星和Ca^2＋对蛋白质构象的影响等提供了重要信息。     

表柔比星、羟喜树碱、顺铂对人膀胱癌细胞株的相互作用

目的观察表柔比星(epirubicin,EPI、羟喜树碱(hydroxy-camptothecin,HCPT)、顺铂(cisplatinum,DDP)在体外对人膀胱癌细胞株(T24)的相互作用.方法采用四甲基偶氮唑蓝(MTT)法利用中效原理判断药物联合应用的效果及药物对膀胱癌细胞株粘贴力的影响.结果3种药物单独应用随着药物剂量的增加,其效应也增加;EPI与HCPT或DDP联合时,两药大剂量(大于中效剂量)合用时可产生拮抗作用,小剂量(小于中效剂量)合用时可产生协同作用;HCPT与DDP联合时,在适当剂量(中效剂量×10-2～中效剂量)合用时可产生协同作用;两药合用时的浓度比例及给药时间次序不同均会影响效应的大小;3种药物单用或合用均会使肿瘤细胞粘贴力下降,其下降程度与用药配伍情况有关.结论两种药物合用时可以产生协同或拮抗作用,且效应大小与两药浓度比例及给药时间次序有关;3种药物均可降低肿瘤细胞的侵袭能力.     

荧光光谱法研究顺铂与牛血清白蛋白的键合

摘 要 目的：探讨在人体生理条件下顺铂与牛血清白蛋白(BSA)的结合作用。 方法: 采用荧光光谱法研究顺铂与BSA的作用机制;考察其结合常数、结合位点数和作用力类型;考察顺铂对BSA构象的影响。结果: 顺铂对BSA的猝灭过程是形成基态复合物的静态猝灭,顺铂与BSA结合位点数和结合常数分别为1.36×10⁴ L·moL^-1和0.991,两者以氢键和范德华力为主。同步荧光表明两者结合作用影响色氨酸残基所处的微环境。结论:顺铂能与BSA结合并改变BSA的构象。     

荧光光谱法研究安非他酮与人血清白蛋白的相互作用

目的 研究安非他酮与人血清白蛋白(human serum albumin,HSA)的相互作用。方法 通过荧光光谱法研究安非他酮对HSA的荧光猝灭光谱和同步荧光光谱的影响。由Stern-Volmer方程确定安非他酮对HSA的荧光猝灭机制,双对数方程确定反应结合位点和结合常数。根据热力学方程讨论两者间主要的作用力类型。结果 荧光猝灭光谱显示,安非他酮对HSA有猝灭作用,在17 ℃和37 ℃时的猝灭速率常数分别为5.714 8×10³和3.126 1×10³ L·mol^-1·s^-1,反应前后的焓变和熵变均<0,结合点数为1。结论 安非他酮对HSA的猝灭过程为静态猝灭,二者间的结合力主要为氢键和范德华力。     

奥沙利铂联合表柔比星介入治疗原发性肝癌的疗效

目的 探讨奥沙利铂联合表柔比星介入治疗原发性肝癌的疗效.方法 将该院2017年7月至2019年7月51例经导管肝动脉化疗栓塞治疗的原发性肝癌患者分为对照组和观察组.对照组25例予以奥沙利铂联合吉西他滨治疗,观察组26例予以奥沙利铂联合表柔比星治疗.观察两组疗效、肿瘤标志物水平及肝功能.结果 治疗后,观察组总有效率(88...     

顺铂对阿霉素与人血清白蛋白结合的相互作用光谱研究

目的 研究顺铂对阿霉素与人血清白蛋白结合的相互作用。方法 采用荧光光谱法研究不同浓度顺铂对阿霉素与人血清白蛋白结合的相互作用。结果 顺铂与阿霉素对人血清白蛋白都有猝灭作用。顺铂对白蛋白的猝灭方式为动态猝灭,而阿霉素对白蛋白的猝灭方式为静态猝灭。结论 温度为17℃和37℃时,阿霉素与白蛋白的结合常数分别为2.13×104,2.76×10^4 L.mol l,2者的结合位点数为1。当加入不同浓度的顺铂后,阿霉素与白蛋白的结合常数有所变化,而结合位点数仍然为1。     

阿柔比星与人血白蛋白相互作用的特点

目的研究阿柔比星与人血清白蛋白的相互作用特点。方法用荧光猝灭光谱及同步荧光光谱技术测定在不同温度下阿柔比星对人血清白蛋白荧光的猝灭规律。结果阿柔比星对人血清白蛋白荧光呈规律性猝灭,17℃时的n为1.11,K为6.21×104,37℃时的n为1.12,K为6.41×104。阿柔比星使白蛋白的同步光谱中最大发射峰红移。结论阿柔比星与人血清白蛋白只有一个结合位点,表现为疏水作用,两者结合使白蛋白的极性略有增加。     

奥沙利铂联合表柔比星用于介入治疗原发肝癌的临床疗效研究

目的:研究奥沙利铂联合表柔比星用于介入治疗原发肝癌的临床疗效。方法:根据治疗方式不同将某院接收的86例晚期肝癌患者分为观察组与对照组,每组43例。对照组为常规的碘油栓塞瘤阻断供血动脉的方式治疗,观察组使用奥沙利铂联合表柔比星介入治疗术治疗,观察两组的血清甲胎蛋白(AFP)、临床疗效、不良反应。结果:观察组的临床疗效88.37%显著高于对照组65.12%(P<0.05);观察组治疗后的AFP水平明显低于对照组(P<0.05);观察组的不良反应发生率为34.88%,与对照组39.53%对比,不具明显差异(P>0.05)。结论:原发肝癌介入治疗中应用奥沙利铂联合表柔比星,其疗效显著,对患者的AFP水平也具有明显的改善效果,值得临床应用和推广。     

盐酸表柔比星联合奥沙利铂对肝癌HepG2细胞凋亡的抑制作用

目的:探讨盐酸表柔比星联合奥沙利铂对肝癌细胞HepG2的抑制作用.方法:盐酸表柔比星和奥沙利铂单独及联合给药用MTT法测定HepG2细胞的增殖,用Hoechst 33258染色法检测细胞核凋亡情况,用DNA ladder检测DNA的裂解情况.结果:人肝癌HepG2细胞经奥沙利铂、盐酸表柔比星以及两者联合作用后,在不同时间、不同浓度均能出现细胞抑制作用,并且均呈现剂量-时间依赖效应,与单药组相比,联合用药组抑制率明显增高,q值大部分为0.85～1.15,呈现明显的相加作用,在(35+5)μg/mL组作用24 h,(20+2) μg/mL组作用48、72 h时两组实验组q值＜0.85,出现拮抗作用.(25+3) μg/mL组作用24 h为最佳作用时间和作用浓度.结论:奥沙利铂及盐酸表柔比星对肝癌HepG2细胞有增殖抑制及促凋亡作用,两药联合作用表现为相加作用,其机制需进一步研究.     

荧光光谱法分析米诺环素与人血清蛋白的相互作用

［摘要］目的研究不同温度下米诺环素与人血清蛋白（HSA）间的相互作用及其作用机制。方法通过荧光光谱法研究米诺环素对HSA的荧光猝灭光谱和同步荧光光谱,确定荧光猝灭的方式,并根据热力学方程讨论两者间主要的作用力类型。结果米诺环素对HSA荧光呈规律性猝灭,T＝299 K时,Ksv为3.29×104 L&#8226;mol-1,T＝310 K,时Ksv为3.53×104 L&#8226;mol-1。米诺环素使清蛋白的同步光谱中最大发射峰红移。 结论米诺环素对HAS的猝灭机制属于动态猝灭,两者之间的作用力以疏水作用力为主。     

加替沙星与牛血清白蛋白相互作用的研究

目的研究不同酸度条件下, 加替沙星与牛血清白蛋白之间的相互作用.方法采用荧光光谱和紫外光谱法进行研究.结果运用荧光猝灭双倒数图计算了在不同条件下二者的结合常数K, 根据Foster非辐射理论计算在正常生理条件下二者的结合距离r, 并通过热力学参数确定了二者的作用力类型.结论加替沙星与牛血清白蛋白之间有较强的相互作用, 以电荷作用力为主.     

Covalent Binding Between Bucillamine Derivatives and Human Serum Albumin

Purpose. To clarify the mechanism of covalent binding between human serum albumin (HSA) and drugs containing thiol groups, we studied the interactions between HSA and bucillamine (BA) and its derivatives. Methods. To determine the concentration of HSA-drug conjugate, we used columns of N-methylpyridium polymer cross-linked with ethylene glycol dimethacrylate (4VP-Me), and analyzed the reaction between HSA and B A derivatives kinetically. Following pseudo first-order reaction kinetics, the rate constants of reduction of non-mercaptoalbumin (HNA) to mercaptoalbumin (HMA) (k_a) and formation of HSA-drug conjugate (k_c) were determined. Results. Formation of HSA-drug conjugate was observed only for drugs containing one thiol group. In compound IV, the plots of k_a and k_c against pH were found to be linear. The HSA-drug conjugate was affected by various factors such as pK_a, pH, temparture and the microenviroment of Cys³⁴. The increases in k_a and k_c. against pH were mainly due to the increase in mercaptide ion concentration. Further, fatty acid affected the microenviroment of Cys³⁴, which increased HSA-drug formation. Conclusions. Cys³⁴ located in a crevice on the surface of the protein plays an important role on the formation of HSA-drug conjugate. These results may be useful for elucidating the reaction mechanisms between various proteins and thiol compounds.     

Interaction of Citrinin with Human Serum Albumin

Citrinin (CIT) is a mycotoxin produced by several Aspergillus, Penicillium, and Monascus species. CIT occurs worldwide in different foods and drinks and causes health problems for humans and animals. Human serum albumin (HSA) is the most abundant plasma protein in human circulation. Albumin forms stable complexes with many drugs and xenobiotics; therefore, HSA commonly plays important role in the pharmacokinetics or toxicokinetics of numerous compounds. However, the interaction of CIT with HSA is poorly characterized yet. In this study, the complex formation of CIT with HSA was investigated using fluorescence spectroscopy and ultrafiltration techniques. For the deeper understanding of the interaction, thermodynamic, and molecular modeling studies were performed as well. Our results suggest that CIT forms stable complex with HSA (logK ~ 5.3) and its primary binding site is located in subdomain IIA (Sudlow’s Site I). In vitro cell experiments also recommend that CIT-HSA interaction may have biological relevance. Finally, the complex formations of CIT with bovine, porcine, and rat serum albumin were investigated, in order to test the potential species differences of CIT-albumin interactions.     

四环素类药物与人血清蛋白的结合作用研究

目的:探讨四环素类药物(土霉素、美他环素、四环素、多西环素)与人血清蛋白(HSA)的相互作用。方法:利用紫外吸收光谱和荧光光谱研究不同温度下四环素类药物与HSA的结合常数和结合点数,计算焓变(ΔH)、熵变(ΔS);依据Frster非辐射能量转移理论,得到供体与受体间的临界距离R0。结果:热力学参数ΔH<0,ΔS>0;R0分别为土霉素1.82nm,美他环素2.31nm,四环素2.98nm,多西环素2.26nm。结论:四环素类药物都能使HSA的荧光发生猝灭,其猝灭机制为静态猝灭;二者之间的主要作用力为静电引力。     

Recombinant Human Serum Albumin Dimer has High Blood Circulation Activity and Low Vascular Permeability in Comparison with Native Human Serum Albumin

Purpose Human serum albumin (HSA) is used clinically as an important plasma expander. Albumin infusion is not recommended for critically ill patients with hypovolemia, burns, or hypoalbuminemia because of the increased leakage of albumin into the extravascular spaces, thereby worsening edema. In the present study, we attempted to overcome this problem by producing a recombinant HSA (rHSA) dimer with decreased vascular permeability and an increased half-life. Methods Two molecules of rHSA were genetically fused to produce a recombinant albumin dimer molecule. The pharmacokinetics and biodistribution of the recombinant proteins were evaluated in normal rats and carrageenin-induced paw edema mouse model. Results The conformational properties of this rHSA dimer were similar to those for the native HSA (the HSA monomer), as evidenced by the Western blot and spectroscopic studies. The biological half-life and area under the plasma concentration–time curve of the rHSA dimer were approximately 1.5 times greater than those of the monomer. Dimerization has also caused a significant decrease in the total body clearance and distribution volume at the steady state of the native HSA. rHSA dimer accumulated to a lesser extent in the liver, skin, muscle, and fat, as compared with the native HSA. Up to 96 h, the vascular permeability of the rHSA dimer was less than that of the native HSA in paw edema mouse models. A prolonged plasma half-life of the rHSA dimer was also observed in the edema model rats. Conclusions rHSA dimer has a high retention rate in circulating blood and a lower vascular permeability than that of the native HSA.