維生素D受體對(duì)LPS急性腎損傷過(guò)程腎臟氧化應(yīng)激和炎性信號(hào)的調(diào)控作用
發(fā)布時(shí)間：2019-07-09 06:29
【摘要】：目的:本課題在前期成功建立LPS急性腎損傷模型基礎(chǔ)上,通過(guò)深入研究體內(nèi)和體外條件下維生素D3對(duì)LPS誘發(fā)小鼠腎臟和人腎小管上皮細(xì)胞炎性信號(hào)和氧化應(yīng)激基因表達(dá)的抑制效應(yīng),闡明維生素D受體對(duì)LPS急性腎損傷過(guò)程腎臟氧化應(yīng)激和炎性信號(hào)的調(diào)控作用和機(jī)制。方法:取96只小鼠隨機(jī)分到四組,每組24只。LPS處理組小鼠通過(guò)腹腔注射LPS,劑量為2.0 mg/kg;生理鹽水組小鼠通過(guò)腹腔注射生理鹽水;LPS+維生素D3組小鼠注射LPS前48小時(shí)、24小時(shí)和1小時(shí)分別經(jīng)口灌胃給予維生素D3;維生素D3組小鼠注射生理鹽水前48小時(shí)、24小時(shí)和1小時(shí)分別通過(guò)灌胃方法給予維生素D3。各組小鼠于LPS注射后1小時(shí)、6小時(shí)或24小時(shí)使用二氧化碳和頸部脫臼方法處死。取血清及雙側(cè)腎臟,分別檢測(cè)腎功能、MDA、GSH含量、尿素氮及肌酐水平、氧化酶基因及抗氧化酶基因,檢測(cè)腎臟炎性因子和介質(zhì)的表達(dá)、VDR的表達(dá)以及二者之間的相互關(guān)系,檢測(cè)各條炎性通路表達(dá)及其與VDR的相互關(guān)系。結(jié)果:維生素D3預(yù)處理保護(hù)LPS引起的小鼠腎功能損害,激活小鼠腎臟VDR信號(hào)并促進(jìn)其向核內(nèi)轉(zhuǎn)移,減輕LPS引起的腎臟GSH耗竭和蛋白硝化,減少血清和腎臟NO產(chǎn)生、下調(diào)腎臟i NOS表達(dá),有效抑制LPS引起的腎臟氧化酶基因上調(diào)和抗氧化酶基因下調(diào),阻斷LPS引起的腎小管上皮細(xì)胞凋亡,對(duì)LPS引起的腎功能損傷起到保護(hù)作用;維生素D3預(yù)處理抑制LPS引起的小鼠腎炎性因子和介質(zhì)上調(diào),激活小鼠腎臟VDR信號(hào);維生素D3抑制LPS誘導(dǎo)腎小管上皮細(xì)胞炎性因子和介質(zhì)與VDR激活有關(guān),維生素D3以I-κB非依賴方式阻斷LPS誘導(dǎo)腎小管上皮細(xì)胞NF-κB p65向細(xì)胞核轉(zhuǎn)移,維生素D3促進(jìn)腎小管上皮細(xì)胞VDR與NF-κB p65相互作用。結(jié)論:維生素D3抑制LPS急性腎損傷過(guò)程腎臟氧化應(yīng)激及炎性信號(hào),其抑制作用與腎臟VDR信號(hào)激活有關(guān)。
文內(nèi)圖片：
圖片說(shuō)明：VitD3預(yù)處理減輕LPS引起的急性腎損傷
[Abstract]:Aim: based on the successful establishment of LPS acute renal injury model in the early stage, the inhibitory effects of vitamin D _ 3 on inflammatory signal and oxidative stress gene expression in mouse kidney and human tubular epithelial cells induced by LPS in vivo and in vitro were studied, and the regulatory effect and mechanism of vitamin D receptor on oxidative stress and inflammatory signal in kidney during acute renal injury in LPS were clarified. Methods: 96 mice were randomly divided into four groups with 24 mice in each group. The mice in the LPS, treatment group were injected with normal saline through intraabdominal injection, and the mice in the LPS vitamin D 3 group were given vitamin D 3 by oral administration 48 hours, 24 hours and 1 hour before injection of LPS, and the mice in the LPS vitamin D 3 group were given vitamin D 3 by oral administration 48 hours, 24 hours and 1 hour, respectively. Vitamin D 3 mice in vitamin D 3 group were given vitamin D 3 48 hours, 24 hours and 1 hour before injection of normal saline. The mice in each group were killed by carbon dioxide and cervical dislocations 1 hour, 6 hours or 24 hours after LPS injection. Serum and bilateral kidneys were taken to detect renal function, MDA,GSH content, urea nitrogen and creatinine levels, enzyme gene and antioxidant enzyme gene, the expression of inflammatory factors and mediators, the expression of VDR and the relationship between them, and the expression of each inflammatory pathway and its relationship with VDR. Results: vitamin D 3 pretreatment protected renal function damage induced by LPS, activated mouse kidney VDR signal and promoted its transfer to nucleus, alleviated renal GSH depletion and protein nitrification induced by LPS, reduced NO production in serum and kidney, down-regulated renal I NOS expression, effectively inhibited LPS induced up-regulation of renal enzyme gene and down-regulation of antioxidant enzyme gene, and blocked apoptosis of renal tubular epithelial cells induced by LPS. It has protective effect on renal function injury induced by LPS. Vitamin D 3 pretreatment inhibited the upregulation of inflammatory factors and mediators induced by LPS and activated VDR signal in mouse kidney. Vitamin D 3 inhibited LPS induced renal tubular epithelial cell inflammatory factors and mediators related to VDR activation. Vitamin D 3 blocked the nuclear transfer of LPS induced renal tubular epithelial cells NF- 魏 B p65 in an I-kappa B independent manner. Vitamin D 3 promoted the interaction between VDR and NF- 魏 B p65 in renal tubular epithelial cells. Conclusion: vitamin D 3 can inhibit renal oxidative stress and inflammatory signal during acute renal injury in LPS, and its inhibitory effect is related to the activation of VDR signal in kidney.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R692.5
，
本文編號(hào)：2511926
文內(nèi)圖片：
圖片說(shuō)明：VitD3預(yù)處理減輕LPS引起的急性腎損傷
[Abstract]:Aim: based on the successful establishment of LPS acute renal injury model in the early stage, the inhibitory effects of vitamin D _ 3 on inflammatory signal and oxidative stress gene expression in mouse kidney and human tubular epithelial cells induced by LPS in vivo and in vitro were studied, and the regulatory effect and mechanism of vitamin D receptor on oxidative stress and inflammatory signal in kidney during acute renal injury in LPS were clarified. Methods: 96 mice were randomly divided into four groups with 24 mice in each group. The mice in the LPS, treatment group were injected with normal saline through intraabdominal injection, and the mice in the LPS vitamin D 3 group were given vitamin D 3 by oral administration 48 hours, 24 hours and 1 hour before injection of LPS, and the mice in the LPS vitamin D 3 group were given vitamin D 3 by oral administration 48 hours, 24 hours and 1 hour, respectively. Vitamin D 3 mice in vitamin D 3 group were given vitamin D 3 48 hours, 24 hours and 1 hour before injection of normal saline. The mice in each group were killed by carbon dioxide and cervical dislocations 1 hour, 6 hours or 24 hours after LPS injection. Serum and bilateral kidneys were taken to detect renal function, MDA,GSH content, urea nitrogen and creatinine levels, enzyme gene and antioxidant enzyme gene, the expression of inflammatory factors and mediators, the expression of VDR and the relationship between them, and the expression of each inflammatory pathway and its relationship with VDR. Results: vitamin D 3 pretreatment protected renal function damage induced by LPS, activated mouse kidney VDR signal and promoted its transfer to nucleus, alleviated renal GSH depletion and protein nitrification induced by LPS, reduced NO production in serum and kidney, down-regulated renal I NOS expression, effectively inhibited LPS induced up-regulation of renal enzyme gene and down-regulation of antioxidant enzyme gene, and blocked apoptosis of renal tubular epithelial cells induced by LPS. It has protective effect on renal function injury induced by LPS. Vitamin D 3 pretreatment inhibited the upregulation of inflammatory factors and mediators induced by LPS and activated VDR signal in mouse kidney. Vitamin D 3 inhibited LPS induced renal tubular epithelial cell inflammatory factors and mediators related to VDR activation. Vitamin D 3 blocked the nuclear transfer of LPS induced renal tubular epithelial cells NF- 魏 B p65 in an I-kappa B independent manner. Vitamin D 3 promoted the interaction between VDR and NF- 魏 B p65 in renal tubular epithelial cells. Conclusion: vitamin D 3 can inhibit renal oxidative stress and inflammatory signal during acute renal injury in LPS, and its inhibitory effect is related to the activation of VDR signal in kidney.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R692.5
，
本文編號(hào)：2511926
本文鏈接：http://sikaile.net/yixuelunwen/mjlw/2511926.html
最近更新
教材專著
