葡萄籽原花青素对大鼠硒性白内障的抑制作用及其机理研究
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摘要
目的:探讨不同剂量葡萄籽原花青素对大鼠硒性白内障的抑制作用
方法:将80只8日龄的SD大鼠随机分为对照组模型组和GSPE低中高剂量组对照组给予生理盐水皮下注射，模型组于第10日龄起给予亚硒酸钠20μmol/kg颈背部皮下注射，隔日1次，连续3次GSPE各组除给予同样造模外，从第8日龄起还分别给予低剂量组50mg/kg中剂量组100mg/kg高剂量组200mg/kg的GSPE灌胃，每天1次连续14天待乳鼠睁眼后用裂隙灯显微镜观察晶状体的浑浊程度，分级以及拍照，并每天测量晶状体核性浑浊斑块的最大直径变化光镜下HE染色观察各组晶状体组织的细胞形态
结果:模型组全部形成典型的核性白内障，造模成功率100%与模型组相比，GSPE各组的晶状体浑浊程度和核性浑浊斑块的最大直径明显减小（P<0.05或P<0.01或P<0.001）光镜下HE染色发现GSPE干预后，晶状体组织的损伤程度减轻，且与GSPE有剂量关系
结论:该实验证实了GSPE能明显抑制亚硒酸钠引起的核性白内障的形成和发展，且有时间–剂量关系，其最低有效剂量为50mg/kg
目的:探讨葡萄籽原花青素提取物抑制大鼠硒性白内障的机理研究
方法:将80只8日龄的SD大鼠随机分为对照组模型组GSPE低中高剂量组对照组给予生理盐水皮下注射，模型组于第10日龄起给予亚硒酸钠20μmol/kg颈背部皮下注射，隔日1次，连续3次GSPE各组除给予同样造模外，从第8日龄起还分别给予低剂量组50mg/kg中剂量组100mg/kg高剂量组200mg/kg的GSPE灌胃，每天1次连续14天实验结束后测量各组晶状体中丙二醛(MDA)超氧化物歧化酶（SOD）过氧化氢酶（CAT）谷胱甘肽过氧化物酶（GSH-PX）一氧化氮（NO）钙离子（Ca~(2+)）含量及晶状体组织抑制羟自由基(OH-)的能力用免疫组织化学法观察iNOS calpainⅡ蛋白在各组晶状体上皮细胞中（LECs）的表达情况，并用平均吸光度(AOD)反应各组的表达量用实时荧光定量RT-PCR法检测iNOS calpainⅡmRNA在各组晶状体中的表达情况
结果:与对照组比，模型组晶状体中抗氧化酶（SOD CAT GSH-PX）的活性及抑制羟自由基的能力显著下降，同时MDA Ca~(2+) NO的含量和iNOS calpainⅡ蛋白吸光度及mRNA的表达水平显著上升（P<0.01或P<0.001）；与模型组相比，GSPE各组抗氧化酶（SOD CAT GSH-PX）的活性及抑制羟自由基的能力明显升高，同时MDA Ca~(2+) NO的含量和iNOS calpainⅡ蛋白及mRNA的表达水平明显下降（P<0.05或P<0.01或P<0.001），且与GSPE有剂量依赖性
结论:该实验证实了GSPE能显著抑制亚硒酸钠引起的核性白内障的形成，其作用机制可能与增强抗氧化酶（SOD CAT GSH-PX）的活性，阻止脂质过氧化产物MDA及自由基羟基的产生，以及抑制晶状体中iNOS和calpainⅡ的激活有关
Objective: To investigate whether grape seed proanthocyanidin extract (GSPE)prevented selenite-induced cataract formation in rats.
Methods: Eighty eight-day-old Sprague-Dawley rat pups were divided randomly into5groups: control group, model group, low dose, medium dose and high dose of GSPEgroup. Control group received physiological saline subcutaneous injection. Model groupreceived subcutaneous injection of sodium selenite (20μmol/kg body weight) onpostpartum day10, and once every other day for continual three times thereafter. GSPEtreated groups respectivly received GSPE (50,100,200mg/kg body weight) intragastricadministration2days prior to the selenite injection (that is, on postpartum day8), and oncedaily for fourteen consecutive days thereafter. The lenses opacity were observed gradedand photographed under slit lamp microscopy and the maximal diameter of the nuclearcataract plaques was measured. The histomorphology of lenses was observed with HE stainunder light microscope.
Results: The results showed subcutaneous injection of sodium selenite led to severenuclear cataract in model group, and the achievement ratio of the model group was100%.Compared with model group, the degree of lenses opacity and the maximal diameter ofnuclear cataract plaques were significantly reduced in GSPE treated groups（P<0.05orP<0.01or P<0.001）. Moreover, the extent of damage in lenses was marked reduced inGSPE treated groups.
Conclusion: The results suggested that GSPE markedly prevented selenite-inducedcataract formation, and we found the lowest effective dose of GSPE was50mg/kg.
Objective: To investigate whether grape seed proanthocyanidin extract (GSPE)prevented selenite-induced cataract formation and the possible mechanism in rat pups.
Method: Eighty eight-day-old Sprague-Dawley rat pups were divided randomly into5groups: control group, model group, low dose, medium dose and high dose of GSPE group.Control group received physiological saline subcutaneous injection. Model group receivedsubcutaneous injection of sodium selenite (20μmol/kg body weight) on postpartum day10,and once every other day for continual three times thereafter. GSPE treated groupsrespectivly received GSPE (50,100,200mg/kg body weight) intragastric administration2days prior to the selenite injection (that is, on postpartum day8), and once daily forfourteen consecutive days thereafter. The lenses were analyzed for superoxide dismutase(SOD), catalase (CAT), glutathione peroxidase (GSH-PX), malondialdehyde (MDA),calcium (Ca~(2+)), nitric oxide (NO)and anti-hydroxyl radical ability (OH-). The levels ofcalpainⅡ, iNOS protein and mRNA expression in lenses were analyzed byimmunohistochemical as well as real-time quantitative RT-PCR method.
Result: we observed selenite treatment caused a significant decrease in the activitiesof antioxidative enzymes (SOD, CAT, GSH-PX)and anti-OH-ability, accompanied by asignificant increase in the levels of MDA, NO, Ca~(2+)as well as iNOS, calpainⅡprotein andmRNA expression. Administration of GSPE could dose-dependent preserve the activities ofthese antioxidative enzymes and anti-OH-ability, accompanied by a significant reduce inthe levels of MDA, NO, Ca~(2+)as well as iNOS, calpainⅡprotein and mRNA expression（P<0.05or P<0.01or P<0.001）.
Conclusion: The results suggested that GSPE markedly prevented selenite-induced cataract formation, and the possible mechanism may be attributed to its excellentantioxidant activity. Treatment with GSPE could dose-dependent preserve the activities ofthese antioxidative enzymes and reduce the generation of MDA, and inhibite on calpainⅡ,iNOS activation.
方法:将80只8日龄的SD大鼠随机分为对照组模型组和GSPE低中高剂量组对照组给予生理盐水皮下注射，模型组于第10日龄起给予亚硒酸钠20μmol/kg颈背部皮下注射，隔日1次，连续3次GSPE各组除给予同样造模外，从第8日龄起还分别给予低剂量组50mg/kg中剂量组100mg/kg高剂量组200mg/kg的GSPE灌胃，每天1次连续14天待乳鼠睁眼后用裂隙灯显微镜观察晶状体的浑浊程度，分级以及拍照，并每天测量晶状体核性浑浊斑块的最大直径变化光镜下HE染色观察各组晶状体组织的细胞形态
结果:模型组全部形成典型的核性白内障，造模成功率100%与模型组相比，GSPE各组的晶状体浑浊程度和核性浑浊斑块的最大直径明显减小（P<0.05或P<0.01或P<0.001）光镜下HE染色发现GSPE干预后，晶状体组织的损伤程度减轻，且与GSPE有剂量关系
结论:该实验证实了GSPE能明显抑制亚硒酸钠引起的核性白内障的形成和发展，且有时间–剂量关系，其最低有效剂量为50mg/kg
目的:探讨葡萄籽原花青素提取物抑制大鼠硒性白内障的机理研究
方法:将80只8日龄的SD大鼠随机分为对照组模型组GSPE低中高剂量组对照组给予生理盐水皮下注射，模型组于第10日龄起给予亚硒酸钠20μmol/kg颈背部皮下注射，隔日1次，连续3次GSPE各组除给予同样造模外，从第8日龄起还分别给予低剂量组50mg/kg中剂量组100mg/kg高剂量组200mg/kg的GSPE灌胃，每天1次连续14天实验结束后测量各组晶状体中丙二醛(MDA)超氧化物歧化酶（SOD）过氧化氢酶（CAT）谷胱甘肽过氧化物酶（GSH-PX）一氧化氮（NO）钙离子（Ca~(2+)）含量及晶状体组织抑制羟自由基(OH-)的能力用免疫组织化学法观察iNOS calpainⅡ蛋白在各组晶状体上皮细胞中（LECs）的表达情况，并用平均吸光度(AOD)反应各组的表达量用实时荧光定量RT-PCR法检测iNOS calpainⅡmRNA在各组晶状体中的表达情况
结果:与对照组比，模型组晶状体中抗氧化酶（SOD CAT GSH-PX）的活性及抑制羟自由基的能力显著下降，同时MDA Ca~(2+) NO的含量和iNOS calpainⅡ蛋白吸光度及mRNA的表达水平显著上升（P<0.01或P<0.001）；与模型组相比，GSPE各组抗氧化酶（SOD CAT GSH-PX）的活性及抑制羟自由基的能力明显升高，同时MDA Ca~(2+) NO的含量和iNOS calpainⅡ蛋白及mRNA的表达水平明显下降（P<0.05或P<0.01或P<0.001），且与GSPE有剂量依赖性
结论:该实验证实了GSPE能显著抑制亚硒酸钠引起的核性白内障的形成，其作用机制可能与增强抗氧化酶（SOD CAT GSH-PX）的活性，阻止脂质过氧化产物MDA及自由基羟基的产生，以及抑制晶状体中iNOS和calpainⅡ的激活有关
Objective: To investigate whether grape seed proanthocyanidin extract (GSPE)prevented selenite-induced cataract formation in rats.
Methods: Eighty eight-day-old Sprague-Dawley rat pups were divided randomly into5groups: control group, model group, low dose, medium dose and high dose of GSPEgroup. Control group received physiological saline subcutaneous injection. Model groupreceived subcutaneous injection of sodium selenite (20μmol/kg body weight) onpostpartum day10, and once every other day for continual three times thereafter. GSPEtreated groups respectivly received GSPE (50,100,200mg/kg body weight) intragastricadministration2days prior to the selenite injection (that is, on postpartum day8), and oncedaily for fourteen consecutive days thereafter. The lenses opacity were observed gradedand photographed under slit lamp microscopy and the maximal diameter of the nuclearcataract plaques was measured. The histomorphology of lenses was observed with HE stainunder light microscope.
Results: The results showed subcutaneous injection of sodium selenite led to severenuclear cataract in model group, and the achievement ratio of the model group was100%.Compared with model group, the degree of lenses opacity and the maximal diameter ofnuclear cataract plaques were significantly reduced in GSPE treated groups（P<0.05orP<0.01or P<0.001）. Moreover, the extent of damage in lenses was marked reduced inGSPE treated groups.
Conclusion: The results suggested that GSPE markedly prevented selenite-inducedcataract formation, and we found the lowest effective dose of GSPE was50mg/kg.
Objective: To investigate whether grape seed proanthocyanidin extract (GSPE)prevented selenite-induced cataract formation and the possible mechanism in rat pups.
Method: Eighty eight-day-old Sprague-Dawley rat pups were divided randomly into5groups: control group, model group, low dose, medium dose and high dose of GSPE group.Control group received physiological saline subcutaneous injection. Model group receivedsubcutaneous injection of sodium selenite (20μmol/kg body weight) on postpartum day10,and once every other day for continual three times thereafter. GSPE treated groupsrespectivly received GSPE (50,100,200mg/kg body weight) intragastric administration2days prior to the selenite injection (that is, on postpartum day8), and once daily forfourteen consecutive days thereafter. The lenses were analyzed for superoxide dismutase(SOD), catalase (CAT), glutathione peroxidase (GSH-PX), malondialdehyde (MDA),calcium (Ca~(2+)), nitric oxide (NO)and anti-hydroxyl radical ability (OH-). The levels ofcalpainⅡ, iNOS protein and mRNA expression in lenses were analyzed byimmunohistochemical as well as real-time quantitative RT-PCR method.
Result: we observed selenite treatment caused a significant decrease in the activitiesof antioxidative enzymes (SOD, CAT, GSH-PX)and anti-OH-ability, accompanied by asignificant increase in the levels of MDA, NO, Ca~(2+)as well as iNOS, calpainⅡprotein andmRNA expression. Administration of GSPE could dose-dependent preserve the activities ofthese antioxidative enzymes and anti-OH-ability, accompanied by a significant reduce inthe levels of MDA, NO, Ca~(2+)as well as iNOS, calpainⅡprotein and mRNA expression（P<0.05or P<0.01or P<0.001）.
Conclusion: The results suggested that GSPE markedly prevented selenite-induced cataract formation, and the possible mechanism may be attributed to its excellentantioxidant activity. Treatment with GSPE could dose-dependent preserve the activities ofthese antioxidative enzymes and reduce the generation of MDA, and inhibite on calpainⅡ,iNOS activation.
引文
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