發(fā)布時(shí)間：2018-03-21 06:07

  本文選題：斑蟊素　切入點(diǎn)：肝臟損傷　出處：《重慶醫(yī)科大學(xué)》2017年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：目的1.探討斑蟊素急性中毒的病理變化。2.探討斑蟊素致肝臟損傷的可能機(jī)制。方法1.用不同致死量斑蟊素對(duì)昆明小鼠灌胃,顯微鏡下觀察心、肺、肝、脾、腎、腦的病理變化。2.用不同劑量斑蟊素持續(xù)對(duì)昆明小鼠灌胃14天,檢測(cè)其肝功能、肝臟指數(shù)和肝臟病理變化,檢測(cè)ATF-6、XBP1、GRP78、ATF-4、CHOP、BAX、Bcl-2、Caspase3、Caspase8和Caspase9蛋白的表達(dá)。用不同濃度斑蟊素連續(xù)培養(yǎng)人肝細(xì)胞LO2,顯微鏡下觀察其生長(zhǎng)情況,CCK-8檢測(cè)活性,檢測(cè)GRP78和CHOP的mRNA的表達(dá),檢測(cè)GRP78、ATF-4、CHOP、BAX、Bcl-2、Caspase3、Caspase8和Caspase9蛋白的表達(dá)。結(jié)果1.斑蟊素急性中毒小鼠的實(shí)質(zhì)細(xì)胞變性壞死,血管擴(kuò)張淤血、出血等。2.斑蟊素能增高小鼠轉(zhuǎn)氨酶和肝臟指數(shù),導(dǎo)致肝細(xì)胞凋亡及壞死,且程度與其劑量正相關(guān);ATF-6、XBP1、GRP78、ATF-4、CHOP、BAX、Caspase3、Caspase8和Caspase9蛋白的表達(dá)上調(diào),Bcl-2蛋白的表達(dá)下調(diào)(P0.05)。斑蟊素抑制LO2細(xì)胞活性,增高GRP78和CHOP基因mRNA的表達(dá),GRP78、ATF-4、CHOP、BAX、Caspase3、Caspase8和Caspase9蛋白的表達(dá)上調(diào),Bcl-2蛋白的表達(dá)下調(diào)(P0.05)。結(jié)論1.斑蟊素能引起小鼠心、肺、肝、脾、腎、腦等臟器組織損傷病理改變,其中肝臟損傷嚴(yán)重。2.斑蟊素可能主要通過(guò)內(nèi)質(zhì)網(wǎng)應(yīng)激途徑誘導(dǎo)肝細(xì)胞凋亡從而導(dǎo)致肝臟的損傷。
[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.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：D919

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