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吸煙相關(guān)劑量鎘致大鼠肝臟氧化損傷的實驗研究

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  本文關(guān)鍵詞:吸煙相關(guān)劑量鎘致大鼠肝臟氧化損傷的實驗研究 出處:《吉林大學(xué)》2009年碩士論文 論文類型:學(xué)位論文


  更多相關(guān)文章: 吸煙 大鼠 肝臟 氧化損傷


【摘要】: 【目的】應(yīng)用Wistar大鼠建立吸煙相關(guān)劑量鎘動物模型,觀察吸煙相關(guān)劑量鎘對大鼠肝臟結(jié)構(gòu)和功能的影響,并探討其可能的機(jī)制。 【方法】建立吸煙相關(guān)劑量鎘染毒動物模型,分別于染毒第20周、44周處死大鼠,留取血清及肝臟;ICP-MS法檢測肝臟鎘、鋅元素含量;血清AST、ALT含量檢測進(jìn)行肝功能評價;彩色多普勒超聲、組織切片觀察對肝臟形態(tài)學(xué)變化進(jìn)行評價;生化試劑盒檢測肝組織MDA、GSH含量及SOD活力;RT-PCR檢測肝臟組織Bcl-2基因表達(dá);Western Blot檢測肝臟組織MTs表達(dá);免疫組化法檢測肝臟組織Bcl-2、MTs的表達(dá)。 【結(jié)果】1)與生理鹽水組比,20周染毒組肝臟組織中鎘含量顯著升高,p0.01。到44周時染毒組肝組織鎘含量相對于20周染毒組下降,但仍高于44周生理鹽水組,p0.05。2)與生理鹽水組相比,20周染毒組血清ALT明顯升高,p0.05,44周染毒組血清ALT略升高,但差異無統(tǒng)計學(xué)意義。染毒20周及44周組AST與生理鹽水組比較,無明顯變化。3)染毒20周及44周,肝臟彩色多普勒超聲未見明顯異常;HE染色組織學(xué)觀察顯示, 20周染毒組及44周染毒組均出現(xiàn)肝細(xì)胞體積、核體積增大,肝細(xì)胞廣泛發(fā)生顆粒變性,粗顆粒狀的染色質(zhì)位于核膜周邊,在中央靜脈、葉間靜脈周圍有灶狀的淋巴細(xì)胞浸潤,枯否氏細(xì)胞腫大,數(shù)量增加,并見灶狀壞死。4)與生理鹽水組相比,20周及44周染毒組肝組織中GSH含量均明顯下降(P20W0.05, P44W0.01);肝組織總SOD活力均顯著下降(p0.01);MDA含量均顯著增高(p0.05)。5)染毒后MT、Bcl-2在蛋白水平的表達(dá)均增強(qiáng);但Bcl-2 mRNA水平的表達(dá)與生理鹽水組比較,無顯著差異。 【結(jié)論】吸煙相關(guān)劑量鎘可造成肝臟的氧化損傷,同時啟動了機(jī)體抗氧化系統(tǒng),但最終仍不能避免肝功能受損及肝臟組織結(jié)構(gòu)的破壞。該結(jié)果提供了低劑量鎘對肝臟有損傷的實驗依據(jù),對于勸說吸煙人群戒煙及飲食中避免鎘攝入有實際意義。
[Abstract]:[objective] to establish a smoking-related dose cadmium animal model in Wistar rats, to observe the effect of smoking related dose cadmium on the liver structure and function of rats, and to explore its possible mechanism. [methods] the animal model of smoking related dose cadmium exposure was established. The rats were killed at the 20th week of exposure to cadmium, and the serum and liver were collected. The contents of cadmium and zinc in liver were detected by ICP-MS. The liver function was evaluated by the determination of alt in serum. The changes of liver morphology were evaluated by color Doppler ultrasound and histological observation. The content of MDA-GSH and the activity of SOD in liver tissue were detected by biochemical kit. RT-PCR was used to detect the expression of Bcl-2 gene in liver tissue. Western Blot was used to detect the expression of MTs in liver tissue. Immunohistochemical method was used to detect the expression of BCL-2 MTs in liver tissue. [results] 1) compared with the saline group, the cadmium content in the liver tissue of the 20 week exposure group was significantly higher than that of the control group (P 0.01). At 44 weeks, the cadmium content of the liver tissue in the exposure group was lower than that in the 20 week group. But it was still higher than that in the saline group at 44 weeks (p0.05.2) compared with the saline group, the serum ALT in the 20 week exposure group was significantly higher than that in the control group, and the serum ALT level in the 44 week group was slightly higher than that in the control group. However, there was no significant difference in AST between the 20 and 44 week groups compared with the saline group. 3) at 20 and 44 weeks of exposure, there was no obvious abnormality in liver color Doppler ultrasound. Histological observation of HE staining showed that hepatocyte volume was increased in 20 week group and 44 week group, and hepatocytes were widely denatured, and coarse granular chromatin was located around the nuclear membrane. In the central vein, there were focal lymphocytic infiltration around the interlobar vein, Kupffer's cells were enlarged and the number of Kupffer cells increased, and focal necrosis. 4) compared with the saline group. In the 20 and 44 week groups, the content of GSH in liver tissue decreased significantly (P 20W 0.05, P 44W 0.01). The activity of total SOD in liver tissue decreased significantly (P 0.01). The expression of MDA Bcl-2 at protein level was significantly increased after exposure to MDA. However, there was no significant difference in the expression of Bcl-2 mRNA between the saline group and the normal saline group. [conclusion] smoking related dose of cadmium can cause oxidative damage to the liver and activate the antioxidant system. However, the damage of liver function and liver tissue structure can not be avoided in the end. This result provides the experimental evidence of liver injury caused by low dose cadmium. It has practical significance for persuading smokers to quit smoking and avoid cadmium intake in diet.
【學(xué)位授予單位】:吉林大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2009
【分類號】:R363;R575

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