斑蟊素中毒的毒理学初步研究

发布时间：2018-03-21 06:07

本文选题：斑蟊素　切入点：肝脏损伤　出处：《重庆医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的1.探讨斑蟊素急性中毒的病理变化。2.探讨斑蟊素致肝脏损伤的可能机制。方法1.用不同致死量斑蟊素对昆明小鼠灌胃,显微镜下观察心、肺、肝、脾、肾、脑的病理变化。2.用不同剂量斑蟊素持续对昆明小鼠灌胃14天,检测其肝功能、肝脏指数和肝脏病理变化,检测ATF-6、XBP1、GRP78、ATF-4、CHOP、BAX、Bcl-2、Caspase3、Caspase8和Caspase9蛋白的表达。用不同浓度斑蟊素连续培养人肝细胞LO2,显微镜下观察其生长情况,CCK-8检测活性,检测GRP78和CHOP的mRNA的表达,检测GRP78、ATF-4、CHOP、BAX、Bcl-2、Caspase3、Caspase8和Caspase9蛋白的表达。结果1.斑蟊素急性中毒小鼠的实质细胞变性坏死,血管扩张淤血、出血等。2.斑蟊素能增高小鼠转氨酶和肝脏指数,导致肝细胞凋亡及坏死,且程度与其剂量正相关;ATF-6、XBP1、GRP78、ATF-4、CHOP、BAX、Caspase3、Caspase8和Caspase9蛋白的表达上调,Bcl-2蛋白的表达下调(P0.05)。斑蟊素抑制LO2细胞活性,增高GRP78和CHOP基因mRNA的表达,GRP78、ATF-4、CHOP、BAX、Caspase3、Caspase8和Caspase9蛋白的表达上调,Bcl-2蛋白的表达下调(P0.05)。结论1.斑蟊素能引起小鼠心、肺、肝、脾、肾、脑等脏器组织损伤病理改变,其中肝脏损伤严重。2.斑蟊素可能主要通过内质网应激途径诱导肝细胞凋亡从而导致肝脏的损伤。
[Abstract]:Objective 1. To investigate the pathological changes of cantharidin acute poisoning. 2. To explore the possible mechanism of cantharidin induced liver injury. Methods 1.The heart, lung, liver, spleen and kidney of Kunming mice were observed under microscope with different lethal doses of cantharidin. The pathological changes of brain. 2. The liver function, liver index and pathological changes of Kunming mice were measured by gastric perfusion with different doses of cantharidin for 14 days. The expression of caspase8 and Caspase9 proteins in human hepatocytes were assayed by ATF-6, XBP1, GRP78, ATF-4, Bcl-2Caspase3Caspase8 and Caspase9 proteins. LO2 cells were cultured continuously with different concentrations of Cantharidin, and their growth was observed under microscope. The activity of CCK-8 and the expression of mRNA in GRP78 and CHOP were detected. To detect the expression of caspase8 and Caspase9 protein in GRP78 / ATF-4 / CHOPP-BAX-Bcl-2Caspase3 / Caspase3Caspase3.Results 1.The denaturation and necrosis of parenchyma cells, vasodilation and congestion, bleeding and so on in mice with acute cantharidin poisoning can increase the levels of transaminase and liver index, and induce apoptosis and necrosis of liver cells in mice with acute cantharidin poisoning. 2. The degree of ATF-6 XBP1 was positively correlated with the dose of ATF-6, XBP1, GRP78, ATF-4, BAXP3, Caspase8 and Caspase9, and up-regulated the expression of Bcl-2 protein and down-regulated the expression of Bcl-2 protein. Cantharidin inhibited the activity of LO2 cells. To increase the expression of GRP78 and CHOP gene mRNA and to up-regulate the expression of Caspase3, Caspase8 and Caspase9. Conclusion: 1. Cantharidin can induce pathological changes of heart, lung, liver, spleen, kidney, brain and other organs in mice. Cantharidin may induce hepatocyte apoptosis mainly through endoplasmic reticulum stress and lead to liver damage.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：D919

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