机构地区:[1]扬州市职业大学医学院,江苏扬州225000 [2]扬州大学医学院/江苏省非编码RNA基础与临床转化重点实验室/扬州大学转化医学研究院,江苏扬州225000
出 处:《淮海医药》2023年第4期331-336,340,共7页Journal of Huaihai Medicine
基 金:国家自然科学基金资助项目(31071216);江苏省大学生科创基金资助项目(202211117079Y/202111117069Y)。
摘 要:目的:探讨人参皂苷Rg3对鱼藤酮纳米脂质载体诱导的帕金森病模型大鼠黑质神经元的保护作用。方法:采用雄性成年大鼠(SD)36只,随机分为对照组、模型组、低剂量组、中剂量组、高剂量组和阳性药物组,每组6只,分别编号1~6号。各组大鼠均于造模前3 d开始给药,每天1次,连续31 d,低剂量组给予3 mg/kg Rg3灌胃,中剂量组给予6 mg/kg Rg3灌胃,高剂量组给予12 mg/kg Rg3灌胃,阳性药物组给予11 mg/kg司来吉兰灌胃,对照组及模型组给予同等剂量羧甲基纤维素钠(CMC-Na)灌胃。灌胃3 d后,除对照组外其余5组大鼠均皮下注射鱼藤酮纳米脂质载体(R-NLC),首剂量给予0.5 mg/kg,第2次给予0.8 mg/kg,此后每次1 mg/kg,2 d一次,连续28 d,对照组皮下注射同等剂量空白纳米脂质载体。采用肌僵直实验和外观行为表现评分考察外观行为学表现;黑质HE染色和透射电镜观察神经元形态和细胞超微结构情况。结果:给药28 d后,模型组外观行为表现评分高于对照组(P<0.05),Rg3低、中、高剂量干预后,外观行为表现评分低于模型组(P<0.05)。肌僵直实验中,模型组大鼠比对照组大鼠移动潜伏期时间延长(P<0.05),而Rg3低、中、高剂量组移动潜伏期时间低于模型组(P<0.05)。HE染色可见,与对照组相比,模型组大鼠黑质正常神经元数目减少,神经元有早期细胞凋亡的特征,Rg3干预能避免模型大鼠黑质神经元形态的变化,减少细胞凋亡的产生,使存活的神经元数目增多。透射电镜结果显示,与对照组相比,模型组大鼠黑质神经元出现细胞凋亡特征,经过低、中、高剂量Rg3干预,大鼠黑质神经元的超微结构基本正常,未见细胞凋亡特征。结论:Rg3对R-NLC诱导的黑质能神经元损伤有保护作用,可减少神经元的凋亡。Objective:To investigate the protective efect of ginsenoside Rg3 on substantia nigra neurons in rats with Parkinson's disease induced by rotenone nanostructured lipid carriers.Methods:36 Sprague Dawley(SD)male adult rats were randomly divided into a control group,a model group,a lowdose group,a medium-dose group,a high-dose group and a positive drug group,with 6 rats in each group and numbered 1~6,respectively.All the rats in each group were administrated 3 days before modeling,once a day for 31 days.The low-dose group was administrated with 3mg/kg Rg3 by gavage,the medium-dose group with 6 mg/kg Rg3 by gavage,the high-dose group with 12 mg/kg Rg3 by gavage,and the positive drug group with 11 mg/kg selegiline by gavage.The control group and model group were given the same dose of Carboxymethylellulose sodium(CMC-Na)by gavage.Three days after the gavage,except for the control group,the other 5 groups were injected subcutaneously with rotenone nanostructured lipid carriers(R-NLC).The first dose was0.5 mg/kg,the second dose was 0.8 mg/kg,fllowved by 1 mg/kg each time,once every 2 days for 28 days.The control group was injected subcutaneously with the same dose of blank nano lipid carrier.The appearance and behavior were examined by muscle ri-gidity test and appearance behavior performance score.The morphology and ultrastructure of neurons in substantia nigra were observed by HE staining and transmission electron microscopy.Results:28 days after the administration,behavioral scores in the model group were higher than those in the control group(P<0.05),and behavioral scores were lower than those in the model group after low-dose,medium-dose and high-dose Rg3 intervention(P<0.05).In muscle rigidity test,the movement latency of rats in the model group was longer than that in the control group(P<0.05),and the movement latency in Rg3 low-dose,medium-dose and high-dose groups was shorter than that in the model group(P<0.05).HE staining showed that compared with the control group,the number of normal neurons in the substant
关 键 词:帕金森病 人参皂苷RG3 细胞凋亡 神经保护 鱼藤酮
分 类 号:R742.5[医药卫生—神经病学与精神病学] R971.6[医药卫生—临床医学]
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