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吴茱萸碱衍生物纳米粒的多功能性药效学研究
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作者 杨兰 陈冉 +2 位作者 施宇涛 张景勍 胡雪原 《重庆医科大学学报》 CAS CSCD 北大核心 2020年第2期217-221,共5页
目的:研究吴茱萸碱丁酰基衍生物(evodiamine butyryl derivative,EAB)和吴茱萸碱丁酰基衍生物固体脂质纳米粒(evodiamine butyryl derivative-loaded lipid nanoparticles,EABLN)在大鼠体内的多功能性药效学行为。方法:采用薄膜超声法制... 目的:研究吴茱萸碱丁酰基衍生物(evodiamine butyryl derivative,EAB)和吴茱萸碱丁酰基衍生物固体脂质纳米粒(evodiamine butyryl derivative-loaded lipid nanoparticles,EABLN)在大鼠体内的多功能性药效学行为。方法:采用薄膜超声法制备EABLN,对制剂的外观、粒径、电位和包封率进行检测。将32只SD雄性大鼠随机分为正常组、模型组、EAB治疗组、EABLN治疗组,每天监测大鼠的体质量变化。治疗组先连续口服灌胃给药治疗1周后,再口服灌胃次黄嘌呤并皮下注射氧嗪酸钾后成功造就了大鼠的高尿酸血症模型,检测血清中尿酸(uric acid,UA)、血肌酐(serum creatinine,CR)、尿素氮(usea nitrogen,BUN)、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low density lipoprotein,LDL)、高密度脂蛋白(high density lipoprotein,HDL)、谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)水平,并进行心、肝、脾、肺、肾、脑组织病理学检查。结果:电镜结果显示,EABLN制备成功。体质量曲线结果显示不同组别对大鼠体质量影响未见不同,但4个组别在7个时间点上体质量有差异。生化指标结果显示,模型组UA、CR、BUN水平明显高于其他各组,差异有统计学意义(F=20.080,F=8.459,F=7.169;P=0.000,P=0.007,P=0.012);4组间的血清ALT、AST水平均无统计学差异(F=1.701,F=3.528;P=0.244,P=0.068)。4组间的TC、TG、LDL和HDL水平均无统计学差异(F=3.069,F=0.398,F=0.191,F=3.291;P=0.091,P=0.758,P=0.899,P=0.079)。病理组织学检查表明,模型组的肾单位完整性被严重破坏,而经EABLN治疗后,逆转了高尿酸血症对肾脏的损害,且EABLN不会对心、肝、脾、肺、脑造成病变。结论:EABLN首次被发现能用于治疗高尿酸血症及其所引发的并发症。 展开更多
关键词 吴茱萸碱丁酰基衍生物 吴茱萸碱丁酰基衍生物固体脂质纳米粒 药效学
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尿酸酶纳米粒在大鼠体内的药代动力学及生物等效性研究 被引量:1
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作者 曹鑫 杨兰 +2 位作者 钟彩灵 陈云 张景勍 《中国临床药理学杂志》 CAS CSCD 北大核心 2021年第18期2486-2489,共4页
目的研究尿酸酶(uricase,UR)及其脂质纳米粒(uricase liposome nano-particles,URLP)并分析URLP在雄性大鼠体内的药代动力学过程和生物等效性。方法使用薄膜分散法制备URLP,测定其粒径、ζ电位及包封率。SD大鼠分别静脉给予URLP和UR后,... 目的研究尿酸酶(uricase,UR)及其脂质纳米粒(uricase liposome nano-particles,URLP)并分析URLP在雄性大鼠体内的药代动力学过程和生物等效性。方法使用薄膜分散法制备URLP,测定其粒径、ζ电位及包封率。SD大鼠分别静脉给予URLP和UR后,测定各个时间点大鼠血液中尿酸酶(uricase,UR)的活性,并计算URLP的药代动力学参数及生物等效性。结果URLP粒径均一,平均粒径为(286.90±7.19)nm,平均包封为率为(80.01±3.21)%,ζ电位为(-29.63±1.00)mV。URLP和UR经尾静脉注射给药后,主要药代动力学参数AUC0-∞分别为(242.83±78.21)和(210.22±53.37)μg·L^(-1)·h,Cmax分别为(10.61±0.53)和(7.83±1.87)μg·L^(-1),Tmax分别为(0.29±0.18)和(0.17±0.08)h,URLP的相对生物利用度为115.51%。结论将UR制备成URLP后延长了UR在大鼠体内的循环半衰期,提高了UR在大鼠体内的生物利用度,且URLP和游离UR不具有生物等效性。 展开更多
关键词 尿酸酶 脂质体 药代动力学 生物等效性 高尿酸血症
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The relationship between the contents of 13 amino acids in brain tissues and the progression of NAFLD via C57BL/6 model mice
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作者 Suqiong Huang Jingyuan Wan +3 位作者 Tingting Du Tao Gong Jing Zhang Xinhui Jiang 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2022年第6期441-451,共11页
Non-alcoholic fatty liver disease(NAFLD)is the steatosis of liver parenchyma unrelated to alcoholism,autoimmunity,and viral infection.It is also a metabolism-related syndrome,which has an unseparated relationship with... Non-alcoholic fatty liver disease(NAFLD)is the steatosis of liver parenchyma unrelated to alcoholism,autoimmunity,and viral infection.It is also a metabolism-related syndrome,which has an unseparated relationship with adipose tissue dysfunction and obesity.Hepatic encephalopathy(HE)is one of the severe complications of chronic liver disease and one of the end-stage syndromes of liver disease.Some researchers have suggested that NAFLD,like other forms of liver injury,may be related to the metabolic disorder of branched-chain amino acids(BCAAs),which have been approved to be associated with HE influencing ammonia and energy metabolism.However,several studies have revealed the relationship among amino acids in serum,HE,and chronic liver disease;there are few studies on the contents of amino acids in brain tissues of an animal model with NAFLD.In the present research,we established a NAFLD mouse model with C57 BL/6 mice and determined the contents of 13 amino acids in brain tissues of model mice by HPLC-FLD derivatization method using ortho-phthalaldehyde(OPA)to explore the relationship between the contents of amino acids in brain tissues and the progression of NAFLD.Moreover,the study showed that the changes of amino acid contents in the brain of the C57 BL/6 mice were associated with the advancement of NAFLD,and this change might be related to the mechanism of HE. 展开更多
关键词 NAFLD Amino acids BCAAs Animal model HE
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