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ID:34037019
大小:2.65 MB
页数:49页
时间:2019-03-02
《calpain-1、caspase-3在慢性氟中毒大鼠肾损伤机制中的作用研究》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、《中国图书资料分类法》单位代码:10660分类号:R363.2+1学号:S100078贵阳医学院2013届硕士学位论文Calpain-1、Caspase-3在慢性氟中毒大鼠肾损伤机制中的作用研究研究生:杨小蓉导师:于燕妮教授李晓松主任医师年级:2010级专业:病理学与病理生理学2013年5月20日2013届硕士研究生毕业论文目录摘要„„„„„„„„„„„„„„„„„„„„„„„1前言„„„„„„„„„„„„„„„„„„„„„„„3材料与方法„„„„„„„„„„„„„„„„„„„„„„7结果„„„„„„„
2、„„„„„„„„„„„„„„„„„19讨论„„„„„„„„„„„„„„„„„„„„„„„„24结论„„„„„„„„„„„„„„„„„„„„„„„„30参考文献„„„„„„„„„„„„„„„„„„„„„„„31致谢„„„„„„„„„„„„„„„„„„„„„„„35英文摘要„„„„„„„„„„„„„„„„„„„„„„„36在读期间参与课题及发表文章„„„„„„„„„„„„„„38缩略词表„„„„„„„„„„„„„„„„„„„„„„„39论文原创性声明„„„„„„„„„„„„„„„„„„„„40附:综述„„„
3、„„„„„„„„„„„„„„„„„„„41-1-2013届硕士研究生毕业论文Calpain-1、Caspase-3在慢性氟中毒大鼠肾损伤机制中的作用研究专业:病理学与病理生理学姓名:杨小蓉导师:于燕妮教授李晓松主任医师摘要目的通过检测氟中毒大鼠肾组织中钙依赖性蛋白酶-1(Calpain-1)、半胱氨酸天冬氨酸特异性蛋白酶-3(Caspase-3)的蛋白及mRNA表达情况,深入探讨慢性氟中毒肾脏病变的分子机制,为地方性氟中毒的预防和治疗提供理论依据。方法用不同浓度的含氟水饲养大鼠8个月,观察氟斑牙发生情况
4、及测定尿氟、骨氟含量,明确氟中毒模型建立成功后处死大鼠;光镜观察肾组织形态学改变;免疫组织化学(Immunohistochemistry,IHC)SABC法检测肾组织中Calpain-1和Caspase-3的蛋白表达水平;用原位杂交技术测定Calpain-1和Caspase-3的mRNA表达水平;原位末端转移酶标记法(Transferase-mediateddUTP-bintin,TUNEL)定位并计数肾组织中凋亡细胞个数;流式细胞仪检测肾组织中细胞凋亡率。结果1、实验组大鼠出现不同程度氟斑牙损害,且高
5、氟组重于低氟组;染氟组大鼠尿氟、骨氟含量明显高于对照组,各组间比较差异有统计学意义(P<0.05)。2、HE结果显示氟中毒大鼠肾脏病变主要分布于皮髓质交界处及髓质,肾小管上皮细胞出现不同程度的肿胀等改变;高氟组甚至可见间质明显充血。IHC发现Calpain-1、Caspase-3在肾小管上皮细胞胞浆呈阳性着色,平均灰度计量显示,与对照组比较,染氟组高于对照组,差异有统计学意义(P<0.05),且高氟组明显高于低氟组。原位杂交显示,与对照组比较,染氟组Calpain-1、Caspase-3mRNA表达高于
6、对照组,差异有统计学意义(P<0.05),且高氟组明显高于低氟组,与-2-2013届硕士研究生毕业论文蛋白表达水平一致。3、流式细胞仪及TUNEL显示,与对照组比较,高氟组肾组织细胞总凋亡率及肾小管上皮细胞凋亡率均高于对照组,差异有统计学意义(P<0.05),且高氟组明显高于低氟组。结论慢性氟中毒可引起肾脏皮髓质交界处及髓质的肾小管上皮细胞肿胀、肾小管管腔狭窄变形、间质充血明显等形态改变,并可致肾小管上皮细胞凋亡增加,其机制可能与肾小管上皮细胞胞浆中Calpain-1和Caspase-3蛋白及mRNA的
7、异常表达有关。关键词:慢性氟中毒;Calpain-1、Caspase-3;肾小管上皮细胞;凋亡-3-2013届硕士研究生毕业论文前言地方性氟中毒(简称地氟病)是指长期摄入过量的氟所致的慢性全身中毒性病变,在世界各地,由于地理环境、生活方式等因素的影响,都有本病的发生,其中我国是氟中毒流行最为严重的国家之一,而贵州毕节地区为我国重病区。地氟病是严重危害人类身体健康的疾病,主要分为饮水型氟中毒、燃煤型氟中毒和饮茶型氟中毒三类。慢性氟中毒不仅会引起机体的骨相损害,同时还会造成机体非骨相损害,如消化系统、泌尿系
8、统、神经系统等,其中肾脏是氟的主要排泄器官,因此,氟对肾脏的影响,不仅关系肾脏形态和功能本身,更关系到氟在全身的代谢平稳。慢性氟中毒肾脏损伤可能的机制有:1、氧化应激:在正常情况下,体内自由基的产生和清除是平衡的,一旦氧自由基产生过多或抗氧化体系出现故障,体[12][3]内氧自由基代谢就会出现失衡,称氧化应激-。陈扬等实验发现氟中毒肝肾组织的损伤为氧化应激所致。2、细胞凋亡:氟可致机体多器官组织细胞发生凋[4-5]亡,如肾、骨、肺及胰腺等。
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