铅致河南华溪蟹卵巢氧化损伤与细胞凋亡的研究
摘要
本文采用亚急性毒性体外暴露的方法,研究了铅(pb2+)对河南华溪蟹(Sinopotamon henanense)卵巢组织器官的氧化损伤和细胞凋亡。实验设置了5个浓度组(3.675、7.35、14.70、29.40和58.80mg.L-1)和1个对照组,在3个时间段(5、10和15d),对超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)活力和丙二醛(MDA)含量进行了检测。为了进一步探究卵巢在氧化应激情况下引发的细胞凋亡现象,对卵巢细胞中H2O2含量、抗O2-能力和抑制OH产生的能力进行了测定。同时,分别采用苏木素-伊红(H.E.)染色法和琼脂糖凝胶电泳法,从细胞形态学水平和生化水平观察了卵细胞的凋亡情况。在此基础上,对处理10d不同浓度pb2+胁迫下卵巢组织中结构型一氧化氮合酶(cNOS)、诱导型一氧化氮合酶(iNOS)、总一氧化氮合酶(T-NOS).半胱天冬酶-3(Caspase-3)和半胱天冬酶-9(Caspase-9)活性进行了测定,旨在初步阐释pb2+诱导卵巢细胞凋亡的机制。结果显示：
(1)随着pb2+浓度增加和处理时间的延长,卵巢中SOD、CAT活力表现为低浓度激活,高浓度抑制,即先升后降的变化规律,GPx活力在5d、10d先升后降,在15d活力不断下降。MDA含量随着染毒时间的延长和浓度的升高逐渐增多。三种抗氧化酶活力的变化趋势和MDA含量的增加,表明卵巢受到的氧化损伤程度在不断加深。
(2)卵巢中H202含量随pb2+浓度增加和时间延长不断上升；反之,抗02一能力和抑制OH产生能力受到pb2+抑制活力不断下降。H.E.染色发现,凋亡细胞的核染色质发生不规则的浓缩边集现象；琼脂糖凝胶电泳图谱呈现出凋亡细胞特有的DNA梯带。
(3)pb2+处理10d,伴随浓度的增加,cNOS、iNOS、T-NOS、Caspase-3和Caspase-9的活力逐渐升高。表明铅诱导激活卵巢细胞中的NOS,产生了过量的NO自由基,最终可能通过以依赖Caspase-9介导的线粒体凋亡途径引发了卵巢组织细胞凋亡
结论：
(1)铅可以导致河南华溪蟹卵巢组织发生氧化损伤和卵细胞凋亡。在铅诱导卵细胞凋亡过程中,伴随过量的H202和NO累积,激活了Caspase-9和Caspase-3,表明铅诱导的卵细胞凋亡可能是通过Caspase-9介导的线粒体凋亡途径。
(2) SOD、CAT、GPX活力和MDA含量的变化能够反映铅对水生动物的胁迫程度及毒性,可作为水环境重金属污染早期预警与毒性效应机理研究的生物评估指标。
Lead (Pb2+) is a heavy metal considered as one of the most toxic environmental and industrial pollutants, which causes gonadotoxic effect in animals.
To explore the effects of lead (Pb2+) on the ovary, the freshwater crabs, Sinopotamon henanense, were exposed to0,3.675,7.35,14.70,29.40, and58.80mg-L-1Pb2+for5,10and15d respectively. The activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and the contents of malondialdehyde (MDA) in ovarian tissues were investigated to study the effect of Pb2+on oxidative stress. In order to study Pb2+-induced apoptosis after oxidative damage, the content of H2O2, the capabilities of anti-O2" and inhibit-OH were measured, meanwhile, the changes in ovarian cell apoptosis were measured by the H.E. staining and agarose gel electrophoresis of DNA. In order to preliminarily explore the mechanisms of apoptosis in the ovary of the crab after Pb2+administration, the activities of apoptosis-associated enzymes were investigated including Caspase-3, Caspase-9, constitutive nitric oxide synthase(cNOS), inducible nitric oxide synthase(iNOS) and total nitric oxide synthase(T-NOS). The results were taken as follows:
(1) In the ovary, Pb2+significantly impacted the activities of SOD, CAT and GPx and altered the contents of MDA in the ovary. MDA content was found to increase persistently during Pb2+exposure. Low concentration of Pb2+can significantly increase antioxidant enzymes; however, for crabs exposed to high concentrations of Pb2+, the activities of the three antioxidant enzymes were all inhibited with prolongation of exposure time. The significant buildup of MDA in ovarian tissues following Pb2+exposure is indicative of Pb2+-induced oxidative damages to crab ovary.
(2) The content of H2O2persistently increased following the increase in concentration of lead and prolongation of exposure time; on the contrary, the capabilities of anti-O2and inhibit-OH declined compared to the control. The ovary cells showed typical morphological characteristic of apoptosis:the karyotin became pyenosis and assembled at the edge after exposure to lead by H.E. staining. The Pb2+-induced ovarian apoptotic DNA fragmentation("ladder" pattern) was clearly revealed on the agarose gel.
(3) At day10, compared with control, cNOS, iNOS, T-NOS, Caspase-3and Caspase-9activity gradually increased with increasing concentration of Pb2+. Lead induced a large amount of NO in the ovary of freshwater crab, and led to ovary cell apoptosis, possibly through Caspase-9-dependent mitochondrial pathway.
Conclusions:
(1) The activities of antioxidant enzyme could be strengthened initially and suppressed with the increase of concentration of lead and extension of exposure time. MDA content was found to increase persistently, indicating that the antioxidant system in ovary was damaged and the crab sufferd oxidative damage. Exposure to Pb2+could induce apoptosis of ovary cells of freshwater crab, via the mitochondria-dependent apoptosis pathway initiated by the activation of Caspase-9and Caspase-3.
(2) The biochemical parameter of SOD, CAT, GPx and MDA, which could reflect cellular toxicity caused by lead, can be used as a biomarker for heavy metal-induced oxidative damages to aquatic animals.
(1)随着pb2+浓度增加和处理时间的延长,卵巢中SOD、CAT活力表现为低浓度激活,高浓度抑制,即先升后降的变化规律,GPx活力在5d、10d先升后降,在15d活力不断下降。MDA含量随着染毒时间的延长和浓度的升高逐渐增多。三种抗氧化酶活力的变化趋势和MDA含量的增加,表明卵巢受到的氧化损伤程度在不断加深。
(2)卵巢中H202含量随pb2+浓度增加和时间延长不断上升；反之,抗02一能力和抑制OH产生能力受到pb2+抑制活力不断下降。H.E.染色发现,凋亡细胞的核染色质发生不规则的浓缩边集现象；琼脂糖凝胶电泳图谱呈现出凋亡细胞特有的DNA梯带。
(3)pb2+处理10d,伴随浓度的增加,cNOS、iNOS、T-NOS、Caspase-3和Caspase-9的活力逐渐升高。表明铅诱导激活卵巢细胞中的NOS,产生了过量的NO自由基,最终可能通过以依赖Caspase-9介导的线粒体凋亡途径引发了卵巢组织细胞凋亡
结论：
(1)铅可以导致河南华溪蟹卵巢组织发生氧化损伤和卵细胞凋亡。在铅诱导卵细胞凋亡过程中,伴随过量的H202和NO累积,激活了Caspase-9和Caspase-3,表明铅诱导的卵细胞凋亡可能是通过Caspase-9介导的线粒体凋亡途径。
(2) SOD、CAT、GPX活力和MDA含量的变化能够反映铅对水生动物的胁迫程度及毒性,可作为水环境重金属污染早期预警与毒性效应机理研究的生物评估指标。
Lead (Pb2+) is a heavy metal considered as one of the most toxic environmental and industrial pollutants, which causes gonadotoxic effect in animals.
To explore the effects of lead (Pb2+) on the ovary, the freshwater crabs, Sinopotamon henanense, were exposed to0,3.675,7.35,14.70,29.40, and58.80mg-L-1Pb2+for5,10and15d respectively. The activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and the contents of malondialdehyde (MDA) in ovarian tissues were investigated to study the effect of Pb2+on oxidative stress. In order to study Pb2+-induced apoptosis after oxidative damage, the content of H2O2, the capabilities of anti-O2" and inhibit-OH were measured, meanwhile, the changes in ovarian cell apoptosis were measured by the H.E. staining and agarose gel electrophoresis of DNA. In order to preliminarily explore the mechanisms of apoptosis in the ovary of the crab after Pb2+administration, the activities of apoptosis-associated enzymes were investigated including Caspase-3, Caspase-9, constitutive nitric oxide synthase(cNOS), inducible nitric oxide synthase(iNOS) and total nitric oxide synthase(T-NOS). The results were taken as follows:
(1) In the ovary, Pb2+significantly impacted the activities of SOD, CAT and GPx and altered the contents of MDA in the ovary. MDA content was found to increase persistently during Pb2+exposure. Low concentration of Pb2+can significantly increase antioxidant enzymes; however, for crabs exposed to high concentrations of Pb2+, the activities of the three antioxidant enzymes were all inhibited with prolongation of exposure time. The significant buildup of MDA in ovarian tissues following Pb2+exposure is indicative of Pb2+-induced oxidative damages to crab ovary.
(2) The content of H2O2persistently increased following the increase in concentration of lead and prolongation of exposure time; on the contrary, the capabilities of anti-O2and inhibit-OH declined compared to the control. The ovary cells showed typical morphological characteristic of apoptosis:the karyotin became pyenosis and assembled at the edge after exposure to lead by H.E. staining. The Pb2+-induced ovarian apoptotic DNA fragmentation("ladder" pattern) was clearly revealed on the agarose gel.
(3) At day10, compared with control, cNOS, iNOS, T-NOS, Caspase-3and Caspase-9activity gradually increased with increasing concentration of Pb2+. Lead induced a large amount of NO in the ovary of freshwater crab, and led to ovary cell apoptosis, possibly through Caspase-9-dependent mitochondrial pathway.
Conclusions:
(1) The activities of antioxidant enzyme could be strengthened initially and suppressed with the increase of concentration of lead and extension of exposure time. MDA content was found to increase persistently, indicating that the antioxidant system in ovary was damaged and the crab sufferd oxidative damage. Exposure to Pb2+could induce apoptosis of ovary cells of freshwater crab, via the mitochondria-dependent apoptosis pathway initiated by the activation of Caspase-9and Caspase-3.
(2) The biochemical parameter of SOD, CAT, GPx and MDA, which could reflect cellular toxicity caused by lead, can be used as a biomarker for heavy metal-induced oxidative damages to aquatic animals.
引文
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