低劑量銅暴露對大鼠肝功能和炎性因子表達的影響及乳酸菌干預(yù)作用
發(fā)布時間：2018-12-25 21:15
【摘要】：目的:1.探討低劑量的銅暴露對大鼠肝臟功能和肝臟組織炎性因子的影響;2.探討乳酸菌(LAB)對銅暴露引起的大鼠肝臟功能和炎性細(xì)胞因子表達水平的干預(yù)效果。方法:大鼠適應(yīng)性喂養(yǎng)7天后,按體重隨機分為8組:高銅組(14mg/kg)、中銅組(3.5mg/kg組)、低銅組(0.875mg/kg組)、高銅+乳酸菌組(14mg/kg+乳酸菌組)、中銅+乳酸菌組(3.5mg/kg組+乳酸菌組)、低銅+乳酸菌組(0.875mg/kg組+乳酸菌組)、乳酸菌組和空白對照組,每組按相應(yīng)劑量連續(xù)性灌胃硫酸銅和乳酸菌30天。1.實驗結(jié)束后,大鼠腹主動脈處取血,處死大鼠后,取大鼠肝、脾和胸腺等臟器,觀察大鼠肝、脾和胸腺指數(shù);2.對肝臟組織進行石蠟包埋,切片并進行HE染色,顯微鏡觀察肝臟的病理變化;3.檢測血清中的與肝功能相關(guān)的蛋白:谷丙轉(zhuǎn)氨酶(ALT)、谷草轉(zhuǎn)氨酶(AST)和白蛋白(ALB)含量;4.ICP-MS(電感耦合等離子體質(zhì)譜儀)法測定大鼠血清中的銅含量;5.檢測肝臟組織中與氧化應(yīng)激相關(guān)的分子:超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽過氧化物酶(GSH-Px)含量;6.RT-PCR法檢測肝臟組織中白細(xì)胞介素-1β(IL-1β)、白細(xì)胞介素-6(IL-6)、白細(xì)胞介素-10(IL-10)、白細(xì)胞介素-12(IL-12)、超氧化物歧化酶和腫瘤壞死因子αTNF-αm RNA的相對表達量。結(jié)果:1.各組間大鼠的肝臟、脾和胸腺指數(shù)未見明顯差異(P0.05);2.通過觀察肝組織病理切片,發(fā)現(xiàn)高銅組、中銅組和低銅組大鼠肝組織在銅處理下均有不同程度損傷的發(fā)生,其中高銅組最為明顯;在加入乳酸菌干預(yù)后,高銅組大鼠的肝損傷得到一定程度的改善;3.與對照組相比,高銅組、中銅和低銅組的AST、ALT顯著增高(P0.05);ALB降低明顯(P0.05);經(jīng)乳酸菌干預(yù)后,不同劑量銅暴露組中的ALB均顯著升高(P0.05),而只有中銅組、低銅組AST和ALT有明顯改善(P0.05)。4.與對照組相比,不同劑量銅暴露組中的血清銅水平均顯著升高(P0.05);乳酸菌干預(yù)后,三組的血清銅水平均減少,但無統(tǒng)計學(xué)意義(P0.05)。5.與對照組相比,不同劑量銅暴露組中的MDA含量均顯著升高(P0.05),只有高銅組和中銅組的SOD活性和SOD m RNA顯著降低(P0.05);乳酸菌干預(yù)后,在高銅組和中銅組SOD和MDA的水平明顯恢復(fù)(P0.05)。6.不同劑量的銅暴露均導(dǎo)致TNF-α、IL-1β、IL-6和IL-10 m RNA升高,IL-12 m RNA在高銅組中也升高并且有統(tǒng)計學(xué)意義(P0.05);乳酸菌干預(yù)后,TNF-α、IL-1β和IL-6 m RNA均明顯降低(P0.05)。結(jié)論:1.不同劑量的銅處理均可引起AST、ALT和ALB的顯著改變,表明低劑量銅暴露能夠引起大鼠肝臟功能下降;2.乳酸菌干預(yù)后,AST、ALT和ALB均有不同程度的改善,提示乳酸菌對銅暴露引起的肝臟功能下降的保護作用;3.低銅組引起IL-1β、IL-6和IL-10 m RNA表達上升,提示低劑量銅暴露即可引起大鼠肝臟炎性損傷;4.乳酸菌干預(yù)后,IL-1β、IL-6和TNF-αm RNA均明顯降低,提示乳酸菌對銅暴露引起的肝損傷的保護作用可能與炎性細(xì)胞因子的釋放有關(guān)。
[Abstract]:Objective: 1. To investigate the effects of low dose copper exposure on liver function and hepatic inflammatory factors in rats. 2. To investigate the effect of lactic acid bacteria (LAB) on liver function and inflammatory cytokine expression induced by copper exposure in rats. Methods: after 7 days of adaptive feeding, rats were randomly divided into 8 groups according to their body weight: high copper group (14mg/kg), medium copper group (3.5mg/kg group), low copper group (0.875mg/kg group) and high copper lactobacillus group (14mg/kg lactobacillus group). Medium copper lactobacillus group (3.5mg/kg group), low copper lactobacillus group (0.875mg/kg group lactic acid bacteria group), lactic acid bacteria group and blank control group, each group in accordance with the corresponding dose of continuous gastric administration of copper sulfate and lactic acid bacteria for 30 days. 1. At the end of the experiment, blood was taken from the abdominal aorta of the rats. After the rats were killed, the liver, spleen and thymus were taken and the indexes of liver, spleen and thymus were observed. 2. The liver tissue was embedded in paraffin, sectioned and stained with HE, and the pathological changes of liver were observed by microscope. 3. Serum proteins related to liver function: glutamate-pyruvic transaminase (ALT), aspartate aminotransferase (AST) and albumin (ALB), serum copper (Cu) in rats by 4.ICP-MS (inductively coupled plasma mass spectrometer). The contents of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in liver tissues were determined. Interleukin-1 尾 (IL-1 尾), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-12 (IL-12) in liver tissue were detected by 6.RT-PCR. The relative expression of superoxide dismutase and tumor necrosis factor 偽 TNF- 偽 m RNA. Results: 1. There was no significant difference in liver, spleen and thymus index among groups (P0.05). By observing the pathological sections of liver tissue, it was found that the liver tissues of high copper group, middle copper group and low copper group all had different degrees of damage under copper treatment, among which the high copper group was the most obvious. The liver injury in high copper group was improved to some extent after the intervention of lactobacillus. Compared with the control group, the AST,ALT of high copper group, medium copper group and low copper group was significantly higher (P0.05); ALB decreased significantly (P0.05); After the intervention of lactic acid bacteria, the ALB in copper exposure group increased significantly (P0.05), but only in medium copper group, AST and ALT were significantly improved in low copper group (P0.05). Compared with the control group, the levels of serum copper in different doses of copper exposure group were significantly higher (P0.05); after the intervention of lactic acid bacteria, the serum copper level of the three groups decreased, but there was no statistical significance (P0.05). Compared with the control group, the MDA content in the copper exposure group was significantly higher than that in the control group (P0.05), but the SOD activity and SOD m RNA decreased significantly in the high copper group and the middle copper group (P0.05). After the intervention of lactic acid bacteria, the levels of SOD and MDA in high copper group and middle copper group recovered significantly (P0.05). The levels of TNF- 偽, IL-1 尾, IL-6 and IL-10 m RNA were increased by different doses of copper exposure, and IL-12 m RNA was also increased in high copper group (P0.05). TNF- 偽, IL-1 尾 and IL-6 m RNA were significantly decreased after lactobacillus intervention (P0.05). Conclusion: 1. Different doses of copper could cause significant changes in AST,ALT and ALB, which indicated that low dose copper exposure could induce the decrease of liver function in rats. 2. After the intervention of lactic acid bacteria, both AST,ALT and ALB were improved to some extent, suggesting the protective effect of lactic acid bacteria on liver function decline induced by copper exposure. 3. The expression of IL-1 尾, IL-6 and IL-10 m RNA increased in low copper group, suggesting that low dose copper exposure could induce inflammatory injury in rat liver. 4. IL-1 尾, IL-6 and TNF- 偽 m RNA decreased significantly after the intervention of lactic acid bacteria, suggesting that the protective effect of lactic acid bacteria on liver injury induced by copper exposure may be related to the release of inflammatory cytokines.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R114
本文編號：2391661
[Abstract]:Objective: 1. To investigate the effects of low dose copper exposure on liver function and hepatic inflammatory factors in rats. 2. To investigate the effect of lactic acid bacteria (LAB) on liver function and inflammatory cytokine expression induced by copper exposure in rats. Methods: after 7 days of adaptive feeding, rats were randomly divided into 8 groups according to their body weight: high copper group (14mg/kg), medium copper group (3.5mg/kg group), low copper group (0.875mg/kg group) and high copper lactobacillus group (14mg/kg lactobacillus group). Medium copper lactobacillus group (3.5mg/kg group), low copper lactobacillus group (0.875mg/kg group lactic acid bacteria group), lactic acid bacteria group and blank control group, each group in accordance with the corresponding dose of continuous gastric administration of copper sulfate and lactic acid bacteria for 30 days. 1. At the end of the experiment, blood was taken from the abdominal aorta of the rats. After the rats were killed, the liver, spleen and thymus were taken and the indexes of liver, spleen and thymus were observed. 2. The liver tissue was embedded in paraffin, sectioned and stained with HE, and the pathological changes of liver were observed by microscope. 3. Serum proteins related to liver function: glutamate-pyruvic transaminase (ALT), aspartate aminotransferase (AST) and albumin (ALB), serum copper (Cu) in rats by 4.ICP-MS (inductively coupled plasma mass spectrometer). The contents of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in liver tissues were determined. Interleukin-1 尾 (IL-1 尾), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-12 (IL-12) in liver tissue were detected by 6.RT-PCR. The relative expression of superoxide dismutase and tumor necrosis factor 偽 TNF- 偽 m RNA. Results: 1. There was no significant difference in liver, spleen and thymus index among groups (P0.05). By observing the pathological sections of liver tissue, it was found that the liver tissues of high copper group, middle copper group and low copper group all had different degrees of damage under copper treatment, among which the high copper group was the most obvious. The liver injury in high copper group was improved to some extent after the intervention of lactobacillus. Compared with the control group, the AST,ALT of high copper group, medium copper group and low copper group was significantly higher (P0.05); ALB decreased significantly (P0.05); After the intervention of lactic acid bacteria, the ALB in copper exposure group increased significantly (P0.05), but only in medium copper group, AST and ALT were significantly improved in low copper group (P0.05). Compared with the control group, the levels of serum copper in different doses of copper exposure group were significantly higher (P0.05); after the intervention of lactic acid bacteria, the serum copper level of the three groups decreased, but there was no statistical significance (P0.05). Compared with the control group, the MDA content in the copper exposure group was significantly higher than that in the control group (P0.05), but the SOD activity and SOD m RNA decreased significantly in the high copper group and the middle copper group (P0.05). After the intervention of lactic acid bacteria, the levels of SOD and MDA in high copper group and middle copper group recovered significantly (P0.05). The levels of TNF- 偽, IL-1 尾, IL-6 and IL-10 m RNA were increased by different doses of copper exposure, and IL-12 m RNA was also increased in high copper group (P0.05). TNF- 偽, IL-1 尾 and IL-6 m RNA were significantly decreased after lactobacillus intervention (P0.05). Conclusion: 1. Different doses of copper could cause significant changes in AST,ALT and ALB, which indicated that low dose copper exposure could induce the decrease of liver function in rats. 2. After the intervention of lactic acid bacteria, both AST,ALT and ALB were improved to some extent, suggesting the protective effect of lactic acid bacteria on liver function decline induced by copper exposure. 3. The expression of IL-1 尾, IL-6 and IL-10 m RNA increased in low copper group, suggesting that low dose copper exposure could induce inflammatory injury in rat liver. 4. IL-1 尾, IL-6 and TNF- 偽 m RNA decreased significantly after the intervention of lactic acid bacteria, suggesting that the protective effect of lactic acid bacteria on liver injury induced by copper exposure may be related to the release of inflammatory cytokines.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R114
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