N-trimethyl chitosan-modified liposomes as carriers for oral delivery of salmon calcitonin

Therapeutic peptide and protein drugs have high specificity and activity in their functions but present challenges in their administration route, requiring development of new delivery systems to improve their bioavailability. The aim of this work was to investigate the role of N-trimethyl chitosan- (TMC-) coated liposomes in the oral administration of calcitonin. TMC with a degree of quaternization around 78% was synthesized and its mucoadhesive properties were examined in vitro using the mucin-particle method, which confirmed that TMC showed mucoadhesion comparable to that of chitosan. TMC-coated liposomes containing calcitonin were prepared and characterized as having a particle size of 262 nm, zeta potential of 35.8 mV and high entrapment efficiency (89.1%). The in vivo evaluation of mucoadhesion was carried out using confocal laser microscopy to observe the residence time and permeation extent after intragastric administration. The results showed that TMC-coated liposomes prolonged the residence time and increased the penetration effect of the liposomal system compared to non-coated liposomes. The study of pharmacological effects confirmed that TMC-coated liposomes increased the area above the blood calcium concentration-time curves (AAC) from 3.13?±?20.50 to 448.84?±?103.56 compared to the calcitonin solution. These results support the feasibility of TMC-coated liposomes as a new oral delivery system for peptide and protein drugs.     

N-三甲基壳聚糖包衣阿霉素脂质体与普通脂质体的抗肿瘤活性比较

目的:比较N-三甲基壳聚糖(TMC)包衣的盐酸阿霉素(ADM)脂质体与普通ADM脂质体的抗肿瘤活性。方法:采用硫酸铵梯度法制备ADM脂质体,以不同取代度的TMC进行包衣,采用动物移植性肿瘤实验法,用小鼠H22肝癌细胞接种于小鼠右侧腋下皮下形成实体瘤,考察TMC包衣ADM脂质体和普通脂质体给药后对实体瘤的瘤重抑制率。结果:TMC60、TMC40、TMC20包衣ADM脂质体对小鼠H22肝癌移植瘤的抑瘤率分别为64.3%,57.0%和54.8%,显著高于ADM脂质体组和游离ADM组(36.4%、42.7%)(P<0.05)。结论:TMC包衣ADM脂质体具有较好的抗肿瘤活性。     

辅酶Q10膜修饰脂质体的制备及其抗上皮细胞SRA 01/04凋亡作用研究

目的:制备辅酶Q10(Coenzyme Q10)膜修饰脂质体,并对其体外抗人晶状体上皮细胞(HLECs)SRA 01/04凋亡作用进行研究。方法:采用自制N-三甲基壳聚糖(TMC)为膜修饰材料,乙醇注入法制备TMC修饰辅酶Q10脂质体(TMC-CoQ10-LP),以药物包封率为指标,磷脂用量(A)、磷脂与胆固醇质量比(B)、磷脂与药物质量比(C)及制备温度(D)为考察因素,采用正交设计优化处方;考察优化处方制得制剂的理化性质;将对数生长期的HLECsSRA 01/04随机分为对照组,模型组,低(38μmol/L)、高(76μmol/L)浓度CoQ10给药组,采用MTT法考察制剂对细胞的抗凋亡作用。结果:最优处方为A2%,B4∶1,C10∶1,D50℃;脂质体呈球形或近球形,粒径呈双峰分布,Zeta电位为24.5mV,包封率可达98%;与模型组比较,低、高浓度CoQ10给药组细胞活力分别提高(20.1±6.47)%、(60.6±18.4)%,细胞凋亡率分别降为23.67%、18.35%。结论:本脂质体制备方法简便、处方重现性好、包封率稳定;与低浓度制剂比较,高浓度制剂的抗凋亡作用更为明显。     

N-trimethyl chitosan-modified liposomes as carriers for oral delivery of salmon calcitonin

Therapeutic peptide and protein drugs have high specificity and activity in their functions but present challenges in their administration route, requiring development of new delivery systems to improve their bioavailability. The aim of this work was to investigate the role of N-trimethyl chitosan- (TMC-) coated liposomes in the oral administration of calcitonin. TMC with a degree of quaternization around 78% was synthesized and its mucoadhesive properties were examined in vitro using the mucin-particle method, which confirmed that TMC showed mucoadhesion comparable to that of chitosan. TMC-coated liposomes containing calcitonin were prepared and characterized as having a particle size of 262?nm, zeta potential of 35.8 mV and high entrapment efficiency (89.1%). The in vivo evaluation of mucoadhesion was carried out using confocal laser microscopy to observe the residence time and permeation extent after intragastric administration. The results showed that TMC-coated liposomes prolonged the residence time and increased the penetration effect of the liposomal system compared to non-coated liposomes. The study of pharmacological effects confirmed that TMC-coated liposomes increased the area above the blood calcium concentration-time curves (AAC) from 3.13?±?20.50 to 448.84?±?103.56 compared to the calcitonin solution. These results support the feasibility of TMC-coated liposomes as a new oral delivery system for peptide and protein drugs.     

N-三甲基壳聚糖包衣的盐酸阿霉素脂质体的制备

研制N-三甲基壳聚糖（TMC）包衣的盐酸阿霉素（ADM）脂质体。方法：采用硫酸铵梯度法制备ADM脂质体,以包封率为指标,筛选盐酸阿霉素脂质体最佳处方;合成不同季铵化程度的TMC,并对最佳ADM脂质体进行包衣。结果：未包衣ADM脂质体平均粒径为（378．6±5．2）nm,Zeta电位为（-62．08±2．5）mv,平均包封率为（62．27±1．75）％（n=3）。TMC包衣后,脂质体粒径增大,并随着TMC季铵化程度的增大,Zeta电位显著增大（p＜0．05）;TMC20、TMC40、TMC60包衣脂质体体外释药曲线符合Higuchi方程,分别为：Q=7．6315＋3．7863t1／2（r=0．9292）,Q=6．9647＋3．5709t1／2（r=0．9318）,Q=7．3451＋2．7665t1/2（r=0．9357）。结论：TMC包衣ADM脂质体的制备工艺可行,其表面带有较高正电性,为下一步研究其血管靶向性打下基础。     

季铵化程度对N-三甲基壳聚糖包衣溴吡斯的明脂质体兔体内药动学的影响研究

目的：研究N-三甲基壳聚糖（TMC）的季铵化程度（QD）对TMC包衣溴吡斯的明（PB）脂质体（PBL）在兔体内药动学的影响。方法：采用逆向蒸发法制备PBL,以QD分别为20%、40%及60%的TMC（TMC20、TMC40及TMC60）对PBL进行包衣。30只日本大耳白兔随机分成5组,采用自身交叉对照实验,分别单剂量口服TMC20、TMC40及TMC60包衣PBL、未包衣PBL及市售PB普通片,HPLC法测定血浆中PB的浓度,用DAS 2.1.1软件计算药动学参数和各种TMC包衣PBL及未包衣PBL的相对生物利用度。结果：TMC20、TMC40及TMC60包衣PBL、未包衣PBL及市售PB普通片在兔体内的药动学特征均符合二室模型,主要药动学参数：C_（max）分别为（15.23±0.12）,（15.20±0.22）,（15.13±0.24）,（15.43±0.51）和（17.60±0.48）mg·L~（-1）;t_（max）分别为（4.16±0.10）,（4.28±0.17）,（4.52±0.24）,（4.05±0.15）和（2.33±0.28）h;AUC_（0-x）分别为（233.42±3.88）,（239.78±3.68）,（252.93±5.01）,（222.64±4.24）和（196.55±2.98）mg·h·L~（-1）。与市售PB片相比,TMC20、TMC40及TMC60包衣PBL、未包衣PBL的相对生物利用度分别为118.76%,121.99%,128.68%,113.27%。经方差分析、双单侧t检验和非参数检验,与市售普通片相比,TMC40、TMC60包衣PBL生物利用度显著提高（P〈0.05）,而TMC20包衣PBL及未包衣PBL则无明显变化（P〉0.05）。结论：TMC包衣PBL可显著提高药物兔体内生物利用度,QD对其有显著性影响,随着QD的增大,TMC包衣PBL生物利用度逐渐增大。     

N-三甲基壳聚糖包覆司帕沙星纳米脂质体离体角膜滞留性及刺激性研究

摘 要 目的：对N-三甲基壳聚糖（TMC）包覆司帕沙星（SL）纳米脂质体的角膜滞留性及兔眼刺激性进行考察。方法: 采用悬挂泡技术和束缚泡技术,对TMC包覆SL纳米脂质体、SL纳米脂质体及SL滴眼液在兔离体眼球表面的接触角及解吸附动力学进行研究;以Draize评分法评价3种SL制剂多次给药后对兔眼的刺激性。结果: 离体角膜表面接触角的大小顺序为：SL滴眼液＞SL纳米脂质体＞TMC包覆SL纳米脂质体,与SL滴眼液相比,两种SL纳米脂质体的解吸时间明显延长,且以TMC包覆的SL纳米脂质体解析时间最长。3种SL制剂在多次给药后,对兔眼无明显的刺激性。结论:与普通滴眼液相比,SL纳米脂质体具有较好的角膜滞留性,TMC包覆后,滞留性进一步增强,并具有较好的安全性,值得进一步开发研究。     

鱼藤酮对小鼠小胶质细胞 BV-2存活率及一氧化氮含量的影响

目的：研究鱼藤酮对小鼠小胶质细胞BV-2存活率及一氧化氮含量的影响。方法 BV-2细胞以5×10^7/L密度接种到细胞培养板中,分别加入鱼藤酮0、1×10^-11、1×10^-10、1×10^-9、1×10^-8、1×10^-7、1×10^-6、1×10^-5 mol/L后0、6、12、24、48、72 h等测定细胞存活率。另以1×10^-8 mol/L鱼藤酮干预BV-2细胞48 h,测定上清液中超氧化物歧化酶、过氧化物酶、总巯基、超氧阴离子和NO含量并与未给予鱼藤酮干预的对照组比较。结果5×10^7/L BV-2细胞于0、6、12、24、48、72 h细胞增殖活力分别为0．035±0．001、0．132±0．006、0．334±0．017、1．073±0．044、2．272±0．172、0．776±0．032,可见48 h达到细胞生长曲线的峰值。鱼藤酮（1×10^-6 mol/L ）干预 BV-2细胞24、48、72 h 细胞存活率分别降低至（63．4±10．1）％、（51．7±12．2）％、（33．9±11．2）％;鱼藤酮（1×10^-7 mol/L）干预BV-2细胞72 h细胞存活率降低至（50．8±2．9）％。1×10^-8 mol/L 鱼藤酮干预48 h 后 BV-2细胞上清液一氧化氮水平达（27．6±6．2）μmol/L,明显高于对照组的（13．3±2．5）μmol/L （t＝-2．135, P＝0．044）。结论鱼藤酮在一定浓度范围内可激活小胶质细胞,但是超出此浓度范围时则可能导致小胶质细胞存活率降低。     

Enhancement of paracellular drug transport with highly quaternized N‐trimethyl chitosan chloride in neutral environments: In vitro evaluation in intestinal epithelial cells (Caco‐2)

Previous studies have established that a partially quaternized derivative of chitosan, N‐trimethyl chitosan chloride (TMC), can be used as an absorption enhancer for large hydrophilic compounds across mucosal surfaces. This study evaluates and compares the effects of the degree of quaternization of TMC, in a neutral environment, on the permeability of intestinal epithelial cells in vitro, where normal chitosan salts are ineffective as absorption enhancers. The effects of TMC‐H [61.2% quaternized, (0.05–1.5% w/v)], TMC‐L [12.3% quaternized, (0.5–1.5% w/v)], and chitosan hydrochloride [0.5–1.5% w/v] on the transepithelial electrical resistance (TEER) and permeability, for the hydrophilic model compound [¹⁴C]‐mannitol, of intestinal epithelial Caco‐2 cell monolayers, were investigated at pH values of 6.20 and 7.40. The viability of the monolayers was checked with the trypan blue exclusion technique. At a pH of 6.20, all the polymers caused a pronounced reduction (37–67% at 0.5% w/v concentrations) in the TEER of Caco‐2 cells. On the contrary, at a pH of 7.40, only TMC‐H was able to decrease the TEER values, even in a concentration as low as 0.05% w/v (35% reduction). Comparable results were obtained with the permeation of [¹⁴C]mannitol. Large increases in the transport rate (18–23‐fold at 0.5% w/v concentrations) were found at pH 6.20, whereas only TMC‐H was able to increase the permeation of [¹⁴C]mannitol at pH 7.40 (31–48‐fold at 0.05–1.5% w/v concentrations of TMC‐H). For all the polymers studied, no deleterious effects to the cells could be demonstrated with the trypan blue exclusion technique. It is concluded that highly quaternized TMC is a potent absorption enhancer and the potential use of this polymer, especially in neutral and basic environments where normal chitosan salts are not effective, is expected to be an important contribution to the development of effective delivery systems for hydrophilic compounds such as peptide drugs.     

N-三甲基壳聚糖包覆牛血清白蛋白脂质体的制备及质量影响因素研究

目的:制备N-三甲基壳聚糖(TMC)包覆的牛血清白蛋白(BSA)脂质体,并考察其质量影响因素。方法:采用逆相蒸发法制备BSA脂质体,壳聚糖与碘甲烷进行季胺化反应合成TMC,用于脂质体包衣,制备TMC包覆的BSA脂质体。采用高速离心考马斯亮蓝G-250法测定包封率,考察脂类大豆卵磷脂(PC):胆固醇(CH):磷脂酰丝氨酸(PS)组成比、TMC与脂相质量比、离子强度对脂质体包封率和粒径的影响。结果:所考察因素对粒径和包封率均有影响,以脂类组成PC:CH:PS(8:9:1)、TMC与脂相质量比0.25:1、离子强度小于20 mmol·L~(-1)为宜,所制脂质体包封率为(46.82±2.07)%。结论:TMC可包覆BSA制备脂质体,所得制剂粒径均匀,稳定性好。     

电导率法测定N-三甲基壳聚糖包覆多囊脂质体的包覆效率

目的建立N-三甲基壳聚糖(N-trimethyl chitosan,TMC)含量测定方法,考察TMC包覆多囊脂质体(multivesicular liposomes,MVLs)的包覆效率。方法利用电导率法测定TMC的质量浓度,并对该方法进行线性、精密度和回收率的考察。采用离心法分离游离的TMC与多囊脂质体,计算TMC包覆多囊脂质体的包覆效率,优化TMC包覆质量浓度及孵育时间。结果 TMC质量浓度在0.01～1.00 g.L-1内线性关系良好(r=0.999 7),日内和日间相对标准偏差小于3%(n=5),回收率为98.93%～102.8%(n=5)。TMC包覆质量浓度为5 g.L-1时,孵育12 h,用此方法测定TMC包覆多囊脂质体的包覆效率为23.15%,RSD为4.33%。优化后,最佳TMC包覆质量浓度为5 g.L-1,孵育时间为4 h。结论电导率法可用于测定TMC包覆多囊脂质体的包覆效率。     

博莱霉素脂质体凝胶的制备和体外透皮性比较

目的：研制博莱霉素（BLM）脂质体凝胶,并对其皮肤靶向性进行体外评价。方法：采用逆相蒸发-冻融法制备BLM脂质体,再用卡渡姆940为基质制成BLM脂质体凝胶;以离心法测定BLM脂质体的包封率;以体外透皮渗透释药法,比较BLM脂质体凝胶与BLM普通凝胶的透过作用。结果：BLM脂质体平均粒径为（885．20±12．08）nm,平均包封率为（66．80±1．38）％。在24h内,BLM脂质体凝胶累积透过量（Q）及稳态透皮速率（J）与BLM普通脂质体相比,均明显提高,而在皮肤中的滞留药量也显著提高（P〈0．05）。结论：BLM脂质体凝胶在体外可显著增加BLM的透皮吸收,增加皮肤中的滞留量,值得进一步研究。     

Evaluation of Mucoadhesive PLGA Microparticles for Nasal Immunization

In this study, hepatitis B surface antigen (HBsAg) loaded poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared and coated with chitosan and trimethyl chitosan (TMC) to evaluate the effect of coating material for nasal vaccine delivery. The developed formulations were characterized for size, zeta potential, entrapment efficiency, and mucin adsorption ability. Plain PLGA microparticles demonstrated negative zeta potential. However, coated microparticles showed higher positive zeta potential. Results indicated that TMC microparticles demonstrated substantially higher mucin adsorption when compared to chitosan-coated microparticles and plain PLGA microparticles. The coated and uncoated microparticles showed deposition in nasal-associated lymphoid tissue under fluorescence microscopy. The coated and uncoated microparticles were then administered intranasally to mice. Immune-adjuvant effect was determined on the basis of specific antibody titer observed in serum and secretions using enzyme-linked immunosorbent assay. It was observed that coated particles showed a markedly increased anti-HBsAg titer as compared to plain PLGA microparticles, but the results were more pronounced with the TMC-coated PLGA microparticles.     

一种新四氢异喹啉类化合物H108体外抑制P-糖蛋白功能及对PC12细胞损伤的保护作用

目的 :观察新合成四氢异喹啉衍生物H10 8抑制P 糖蛋白 (P gp)功能及对PC12细胞损伤的保护作用。方法 :测定H10 8对K5 6 2 ADR细胞株及大鼠脑微血管内皮细胞 (RBMECs)内罗丹明 12 3(Rh12 3)积聚的影响 ,考察H10 8逆转P gp介导的多药耐药性及对血脑屏障上P gp药物外排功能的影响。以连二亚硫酸钠 (Na2 S2 O4)建立缺血缺氧损伤模型 ,过氧化氢 (H2 O2 )建立氧化应激损伤模型 ,硝普钠 (SNP)建立NO损伤模型 ,MTT法测定H10 8对三种PC12损伤细胞存活率的影响。结果 :H10 8浓度依赖性地增加K5 6 2 ADR及RBMECs细胞中Rh12 3的累积浓度。并可明显对抗Na2 S2 O4及SNP诱导的PC12细胞损伤 ,增加细胞存活率。结论 :H10 8具有一定的P gp逆转作 ,并可能具有一定的神经保护作用。其有可能成为一种新型、高效 ,特别是用于促进血脑屏障上药物转运的P gp逆转剂     

眼用司帕沙星阳离子脂质体原位凝胶的研制

目的:研制司帕沙星(SF)眼用阳离子脂质体-原位凝胶(ISG)。方法:采用pH梯度法制备SF脂质体(SFL),用季胺化程度为60%的N-三甲基壳聚糖(TMC60)包衣,用正交试验筛选其最佳处方及工艺,再与泊洛沙姆P407为基质的温度敏感材料混合,制备TMC60包衣的SFL-ISG,并对其形态、粒径、Zeta电位、凝胶溶蚀及释药等体外性质进行考察。结果:本品形态圆整,粒径分布均匀,TMC60包衣后Zeta电位由负转正,药物释放和凝胶溶蚀均呈现良好的零级释放特征。结论:本品结合阳离子脂质体与原位凝胶技术成功制备了TMC60包衣的SFL-ISG,为其体内研究奠定了实验基础。     

Preparation of a TK/GCV administration system mediated by transferrin modified pro-cationic liposomes

Transferrin modified pro-cationic liposomes were prepared and used to investigate the effect of targeting therapeutic genes to human hepatoma carcinoma cells in vitro. The main lipid CHETA, cholest-5-en-3beta-yl[2-[[4-[(carboxymethyl)dithio]-1-iminobutyl]amino]ethyl] carbamate (C36H61N3O4S2), was synthesized and used to prepare pro-cationic liposomes. The thymidine kinase (TK) gene loaded pro-cationic liposomes were prepared by first mixing the plasmid DNA and protamine together, and then incubating the resulted polyplexes with blank pro-cationic liposomes preformed by the thin film dispersion-sonication method. Transferrin (Tf) was adsorbed on the surface of pro-cationic liposomes via electrostatic interactions to form transferrin modified pro-cationic liposomes. Cellular association was measured by fluorimetry at excitation and emission wavelengths of 490 and 520 nm, respectively. The viability of TK gene infected cells following administration of ganciclovir (GCV) was investigated by MTT assay. The transferrin modified TK gene pro-cationic liposomes had a mean diameter of 240 +/- 12 nm and zeta potential of -24.10 +/- 2.5 mV (n = 3). The transmission electron microscopy image indicated that most of the liposomes were relatively regular and spherical with a condensed core inside. Cell-associated fluorescence of Tf-liposomes and unmodified liposomes (without transferrin) was 7.8 x 10(6), and 3.2 x 10(6) per milligram protein, respectively. Compared to Lipofectamine 2000 (Invitrogen, USA) the pro-cationic liposomes and transferrin modified pro-cationic liposomes had less cytotoxicity to cells. The transduced TK gene HepG2 cells were more sensitive to GCV than the un-transduced TK gene ones and the human normal Chang liver cells were not affected by the TK/GCV system mediated by procationic liposomes.     

Cadmium-induced induction of cell death in human lens epithelial cells: Implications to smoking associated cataractogenesis

Cadmium is reported to accumulate in human eye tissues suggesting its implication in diverse ocular pathology. Using an in vitro cell culture model we investigated the effects of cadmium on human lens epithelial cells (HLECs) (HLE-B3). We observed cadmium-induced dose- as well as time-dependent decline in HLECs viability which was exacerbated significantly upon reduction of intracellular glutathione levels by buthionine sulfoximine (BSO). There was a dose-dependent significant increase in lactate dehydrogenase (LDH) release from HLECs suggesting cadmium-induced alteration of membrane integrity as well as necrotic cell death. The decline in cell viability was also due to apoptosis of the HLECs as determined by quantifying % apoptotic cells as well as PARP cleavage. Moreover, release of apoptosis inducing factor (AIF) into the cytosol was also detected. Cadmium was also observed to increase oxidative stress, lipid peroxidation and activation of MAPK pathway in HLECs. Antioxidants like N-acetylcysteine (NAC) and α-Tocopherol significantly prevented cadmium-induced toxicity in HLECs. Our findings suggest that cadmium-induced elevated oxidative stress as well as activation of MAPK signaling cascade eventually led to cell death of HLECs through apoptosis as well as necrosis. The loss of HLECs by cadmium could possibly explain its implication in cataract development particularly associated with smoking.     

槲皮素对NIH-3T3细胞氧化损伤的保护作用

目的探讨槲皮素对NIH-3T3细胞氧化损伤的保护作用。方法取处于对数生长期的3T3细胞,平均分为以下四个实验组。槲皮素前保护组(Q1组):先加含有50μmol/L槲皮素培养液培养24h,再换含有0.5mmol/LH2O2的培养液培养30min。槲皮素后保护组(Q2组):先加含有0.5mmol/LH2O2的培养液培养30min;再换含有50μmol/L槲皮素培养液培养24h;H2O2损伤组(H2组):先加含有0.5mmol/LH2O2的培养液培养30min,再换仅含有10%的胎牛血清的培养液培养24h。对照组(C组):仅加10%胎牛血清的DMEM培养液培养24h。收集并裂解各组细胞,检测细胞内T-AOC、SOD、GSH-Px、GSH、NOS、NO、MDA的变化,应用MTT实验检测3T3细胞的生存率。结果Q1与Q2、H2组相比,Q1组细胞内T-AOC、SOD、GSH-Px、GSH均有增加,NOS、NO无明显改变,MDA减少,细胞存活率明显增加。结论槲皮素可能是通过上调抗氧化酶系活性对3T3细胞的氧化损伤产生保护作用。     

N-三甲基壳聚糖包衣多柔比星脂质体肿瘤新生血管靶向性的体内评价

目的：考察N-三甲基壳聚糖（TMC）包衣的多柔比星（ADM）阳离子脂质体抗肿瘤活性及对肿瘤新生血管的靶向性。方法：采用动物移植性肿瘤实验法,建立小鼠H22肿瘤模型,比较TMC包衣脂质体组和其他各给药组的肿瘤抑制率并通过小鼠尾静脉注射异硫氰酸荧光素标记的葡聚糖（FITC—Dextran）,分析肿瘤组织中的在体荧光,定性观察肿瘤新生血管的形态排布情况,定量测定肿瘤组织中的血管相对密度。结果：TMC包衣的ADM脂质体组,其小鼠的瘤重抑制率迭53．47％,显著高于游离药物组和未包衣脂质体组（8．75％,34．88％）（P〈0．05）;给予TMC包衣ADM脂质体的小鼠,其肿瘤新生血管形态良好,排布均匀,血管分支少,而其他给药组的肿瘤新生血管多扭曲,粗细不均,一个节点有多个血管分支等;通过比较不同给药组肿瘤组织黏附的FITC—Dextran量,TMc包衣ADM脂质体组的肿瘤血管密度明显低于游离药物组和未包衣脂质体组（P〈0．05）。结论：TMC包衣的ADM阳离子脂质体不仅具有较强的抗肿瘤活性,而且具有很好的肿瘤新生血管靶向性。     

丹皮酚对过氧化氢诱导的PC12细胞凋亡的抑制作用(英文)

目的探讨丹皮酚对过氧化氢(H2O2)诱导的PC12细胞凋亡的抑制作用及其机制。方法建立H2O2致PC12细胞损伤模型,采用MTT法测定细胞存活率,流式细胞术测定细胞凋亡率及细胞内活性氧含量,化学比色法测定乳酸脱氢酶(LDH)释放量及细胞内丙二醛(MDA)含量。结果PC12细胞经H2O2100μmol.L-1处理10 h可致细胞存活率下降,并能诱导细胞凋亡,LDH释放量及细胞内活性氧和MDA含量明显增加;丹皮酚(12,25和50μmol.L-1)预处理1 h可提高细胞存活率,减少细胞凋亡、LDH释放量及细胞内活性氧和MDA含量。结论丹皮酚对H2O2诱导的PC12细胞凋亡具有抑制作用,该作用可能与其抗氧化作用有关。