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葛根素减轻部分由过氧亚硝基阴离子导致的糖尿病大鼠晶状体上皮细胞凋亡

Puerarin decreases lens epithelium cell apoptosis induced partly by peroxynitrite in diabetic rats

本研究观察葛根素是否减轻部分由过氧亚硝基阴离子(peroxynitrite,ONOO-)导致的糖尿病大鼠晶状体上皮细胞(lens epithelium cell,LEC)凋亡.采用大鼠腹腔注射链脲佐菌素(streptozotocin,STZ)的方法建立糖尿病动物模型.36只大鼠作为对照组,腹腔注射生理盐水;其他72只大鼠腹腔注射STZ(45 mg/kg)后分为STZ组和STZ+葛根素组,每组36只.STZ注射3 d后,STZ+葛根素组大鼠每天腹腔注射葛根素(140 mg/kg).于实验开始后第20、40和60天用裂隙灯检查晶状体的形态学变化后处死动物.用流式细胞仪检测LEC凋亡,用免疫组化方法检测晶状体中ONOO的标志物--硝基酪氨酸(nitrotyrosine,NT)的表达,用基因芯片分析技术检测LEC凋亡相关基因iNOS等的表达.结果发现,对照组大鼠晶状体均透明,各项指标基本正常;STZ组大鼠第20天时即出现晶状体混浊,40~60 d期间混浊不断加重;STZ+葛根素组大鼠20~40 d时晶状体混浊呈加重趋势,但40~60 d以后明显减轻.对照组LEC轻度凋亡,而STZ组凋亡细胞呈持续性增长,STZ+葛根素组大鼠20~40 d时细胞凋亡呈增长趋势,但40~60 d以后明显下降.对照组大鼠晶状体NT未见明显表达;STZ组大鼠NT表达明显加强;STZ+葛根素组大鼠20~40 d时NT表达呈增长趋势,但40~60 d以后明显下降.对照组凋亡相关基因未见明显变化,STZ组凋亡相关基因iNOS表达明显上调.其他凋亡相关基因如BCL-2、SOD表达明显下调,但NF-кB和TNFR1-FADD-caspase信号转导途径明显上调;STZ+葛根素组凋亡相关基因表达则呈相反改变.上述结果表明,在糖尿病大鼠晶状体中有ONOO- 的标志物NT表达,证明糖尿病大鼠LEC凋亡部分由ONOO诱导,这可能是氧化损伤导致白内障形成的新途径.葛根素能够部分逆转ONOO- 对LEC的致凋亡作用,提示葛根素可能是治疗糖尿病性白内障的有效药物,其治疗机制可能与葛根素直接抑制凋亡和对抗ONOO-对糖尿病大鼠LEC的损伤有关.

作 者:
郝丽娜 凌毅群 罗秀梅 毛宇湘 毛绮妍 何守志 凌亦凌 HA Li-Na LING Yi-Qun LUO Xiu-Mei MAO Yu-Xiang MAO Qi-Yan HE Shou-Zhi LING Yi-Ling  
作者单位:
郝丽娜,罗秀梅,HA Li-Na,LUO Xiu-Mei(Ophthalmology Department of Hebei Province People's Hospital,Shijiazhuang 050051,China)
凌毅群,毛宇湘,毛绮妍,凌亦凌,LING Yi-Qun,MAO Yu-Xiang,MAO Qi-Yan,LING Yi-Ling(河北医科大学病理生理教研室,石家庄,050017)
何守志,HE Shou-Zhi(Ophthalmology Department of PLA Hospital,Beijing 100806,China) 
刊 名:
生理学报  ISTIC PKU
英文刊名:
ACTA PHYSIOLOGICA SINICA 
年,卷(期):
2006 58(6) 
分类号:
R3 
关键词:
葛根素 知识脉络  晶状体上皮细胞 知识脉络  糖尿病 知识脉络  白内障 知识脉络  puerarin 知识脉络  lens epithelium cell 知识脉络  diabetes mellitus 知识脉络  cataract 知识脉络 
机标分类号:
R77 R96 
机标关键词:
葛根素过氧亚硝基阴离子糖尿病大鼠大鼠晶状体上皮细胞凋亡diabetic rats凋亡相关基因腹腔注射对照组intraperitoneal injection晶状体混浊signal transduction增长趋势免疫组化方法检测oxidative damage糖尿病性白内障流式细胞仪检测晶状体上皮细胞flow cytometry注射生理盐水 
基金项目:
 
DOI:
 
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