CAJ | 학술논문

目的考察OX26耦联载内吗啡肽的超支化聚甘油-聚乳酸-聚乙醇酸(OX26-EM-HBPG-PLGA)纳米粒细胞毒性及血液相容性,为安全用于动物实验提供依据.方法将纳米粒分为B组(HBPG-PLGA纳米粒)、EP组(EM-HBPG-PLGA纳米粒)、OEP组(OX26-EM-HBPG-PLGA纳米粒)组,分别采用噻唑蓝比色法(MTT法)考察各组纳米粒对大鼠脑毛细血管内皮细胞(BMECs)的细胞毒性、兔血溶血率；通过正常大鼠静脉注射各组纳米粒考察其对血常规和凝血系统的影响.结果 ①不同类型纳米粒对BMECs的细胞毒性呈浓度依赖性；3组纳米粒对细胞都有一定毒性作用,在质量浓度为30～600 μg,/ml范围内,其细胞抑制情况较低且稳定,质量浓度为2 700 μg/ml时,细胞活力明显下降(P＜0.01).②无论纳米粒浓度高低,兔血红细胞溶血率均低于5％,各组差异无统计学意义(P＞0.05),符合医用实验材料的溶血要求.③各组纳米粒对血常规均无影响(P＞0.05).④3组纳米粒低剂量组与对照组比较,各凝血指标差异无统计学意义(P＞0.05).与对照组相比,高剂量组凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)明显延长,纤维蛋白原(Fbg)含量明显下降,差异有统计学意义(P＜0.05),而且与同组低剂量组比较,高剂量组PT、APTT明显延长,Fbg含量明显下降,差异有统计学意义(P＜0.05或P＜0.01).结论较低浓度和合适剂量的OX26-EM-HBPG-PLGA纳米粒对BMECs毒性低微,溶血率低,对大鼠血常规凝血系统没有影响,具有良好的生物安全性.
목적 고찰OX26우련재내마배태적초지화취감유-취유산-취을순산(OX26-EM-HBPG-PLGA)납미립세포독성급혈액상용성,위안전용우동물실험제공의거.방법 장납미립분위B조(HBPG-PLGA납미립)、EP조(EM-HBPG-PLGA납미립)、OEP조(OX26-EM-HBPG-PLGA납미립)조,분별채용새서람비색법(MTT법)고찰각조납미립대대서뇌모세혈관내피세포(BMECs)적세포독성、토혈용혈솔；통과정상대서정맥주사각조납미립고찰기대혈상규화응혈계통적영향.결과 ①불동류형납미립대BMECs적세포독성정농도의뢰성；3조납미립대세포도유일정독성작용,재질량농도위30～600 μg,/ml범위내,기세포억제정황교저차은정,질량농도위2 700 μg/ml시,세포활력명현하강(P＜0.01).②무론납미립농도고저,토혈홍세포용혈솔균저우5％,각조차이무통계학의의(P＞0.05),부합의용실험재료적용혈요구.③각조납미립대혈상규균무영향(P＞0.05).④3조납미립저제량조여대조조비교,각응혈지표차이무통계학의의(P＞0.05).여대조조상비,고제량조응혈매원시간(PT)、활화부분응혈활매시간(APTT)명현연장,섬유단백원(Fbg)함량명현하강,차이유통계학의의(P＜0.05),이차여동조저제량조비교,고제량조PT、APTT명현연장,Fbg함량명현하강,차이유통계학의의(P＜0.05혹P＜0.01).결론 교저농도화합괄제량적OX26-EM-HBPG-PLGA납미립대BMECs독성저미,용혈솔저,대대서혈상규응혈계통몰유영향,구유량호적생물안전성.
Objective To study the cytotoxicity against brain microvessel endothelial cells and blood compatibility in rats of OX26 conjugated endomorphin (EM) loaded hyperbranched polyglycerols-poly(lactic-co-glycolic acid)(HBPG-PLGA) nanoparticles.Methods Prepared nanoparticles were divided into group B (HBPG-PLGA nanoparticles),group EP (EM-HBPG-PLGA nanoparticles) and group OEP (OX26-EM-HBPG-PLGA nanoparticles).The cytotoxicity against brain microvessel endothelial cells (BMECs) of nanoparticles of different groups were measured by MTT test,haemolysis test,normal haemotological parameter and several primary items of coagulation system were tested after nanoparticles of different groups and different dosages injection on rats.Results ①All the three groups of nanoparticles induced decreased cell viability in a dose dependent manner in MTT test,whereas all groups of nanoparticles showed low cytotoxicity against the BMECs during 30 to 600 μg/ml.②There was no significant difference in haemolysis ratio (P＞0.05) and normal haemotological parameter (P＞0.05).③There was no significant difference between the low dosage of all the three groups of nanoparticles and the control group on the function of coagulation system in rats (P＞0.05).④Compared with C group,high dose groups demonstrated longer prothrombin time (PT),activeated partial thromboplasting time (APTT) and lower fibrinogen (Fbg) (P＜0.05).At the same time,compared with the low dose subgroups,PT and APTT were prolonged,Fbg significantly decreased in the high dose subgroups (P＜0.05 or P＜0.01).Conclusion OX26 coupled with EM-HBPG-PLGA nanoparticles showed low cytotoxicity against BMECs and had no significant effect on the coagulation system in rats with low concentration and low dosage.