本文選題：缺血再灌注 + 肝損傷�。� 參考：《錦州醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的探討不同劑量右美托咪定(DEX)預(yù)處理對(duì)小鼠腎臟IRI導(dǎo)致肝損傷的保護(hù)作用及機(jī)制。方法動(dòng)物實(shí)驗(yàn):40只8周齡健康雄性C57 BL/6J小鼠,隨機(jī)均分為5組:sham組、IRI組、25μg/kg Dex組(低劑量)、50μg/kg Dex組(中劑量)和100μg/kg Dex組(高劑量),每組8只。除sham組外,其余各組小鼠均在背部中線兩側(cè)腎區(qū)切口,用玻璃分針鈍性分離腎臟周?chē)∪饨M織和腎筋膜,用無(wú)創(chuàng)傷動(dòng)脈夾輕輕夾閉雙側(cè)腎臟動(dòng)脈血管導(dǎo)致腎缺血,進(jìn)行造模。于手術(shù)后24h處死小鼠,收集血液、腎臟和肝臟組織。檢測(cè)小鼠腎功能和肝功能指標(biāo),HE染色觀察小鼠腎臟和肝臟病理改變,WST-1法檢測(cè)小鼠肝臟組織總超氧化物歧化酶(SOD)活力,TBA法測(cè)定小鼠肝臟組織丙二醛(MDA)含量,比色法測(cè)定小鼠腎臟組織谷胱甘肽過(guò)氧化物酶(GSH-PX)含量,ELISA法檢測(cè)了小鼠肝臟勻漿液內(nèi)炎癥因子TNF-α、MCP-1、和IL-6以及抗炎癥因子IL-10含量,Western-blot方法檢測(cè)分析小鼠肝臟組織Caspase3、Bcl-2和Bax蛋白表達(dá)情況。結(jié)果1.Dex預(yù)處理后可以明顯改善由于腎臟IRI導(dǎo)致的腎功能改變:與sham相比較,IR組小鼠血漿中Scr,Bun和Cys-C顯著升高(P0.01);與IR組相比較,25ug/kg Dex組小鼠血漿中Bun下降不明顯(P0.05),Scr和Cys-C明顯降低(P0.05);50 ug/kg、100 ug/kg Dex組小鼠血漿中Scr,Bun和Cys-C明顯降低(P0.05)。2.Dex預(yù)處理后可以明顯改善由于腎臟IRI導(dǎo)致的肝功能改變:與sham相比較,IR組小鼠血漿中AST和ALT的含量均顯著升高(P0.01);與IR組相比較,25ug/kg Dex、50 ug/kg、100 ug/kg Dex組小鼠血漿中AST和ALT含量均下降比較明顯(P0.05)。3.Dex預(yù)處理后可以明顯改善由于腎臟IRI導(dǎo)致的腎臟結(jié)構(gòu)病變情況:與sham相比較,IR組小鼠病變明顯,HE染色顯示腎臟皮質(zhì)和髓質(zhì)交界處腎小管細(xì)胞壞死脫落;與IR組相比較,25ug/kg Dex、50 ug/kg Dex、100 ug/kg Dex組小鼠腎臟病變明顯得到改善。4.Dex預(yù)處理后可以明顯改善由于腎臟IRI導(dǎo)致的肝臟結(jié)構(gòu)病變情況:與sham相比較,IR組小鼠病變明顯,HE染色顯示IR組小鼠肝臟大量炎性細(xì)胞浸潤(rùn),肝竇擴(kuò)張,少量空泡形成,肝細(xì)胞排列紊亂。與IR組相比較,25ug/kg Dex、50 ug/kg Dex、100 ug/kg Dex組小鼠肝臟病變明顯得到改善。5.Dex預(yù)處理后可以明顯提高肝臟對(duì)氧自由基的清除能力,提高組織內(nèi)總抗氧化能力:與sham相比較,IR組小鼠肝臟中SOD活力和GSH-PX活性明顯降低(P0.05),MDA含量顯著升高(P0.01);與IR組相比較,25ug/kg Dex、50 ug/kg DEX、100 ug/kg Dex組小鼠肝臟中SOD活力和GSH-PX活性明顯升高(P0.05),MDA含量顯著降低(P0.05)。6.Dex預(yù)處理后可以明顯改善肝臟組織的抗炎癥能力:與sham相比較,IR組小鼠肝臟中TNF-α、IL-6、IL-10和MCP-1含量均升高(P0.05);與IR組相比較,25ug/kg Dex、50 ug/kg、100 ug/kg Dex預(yù)處理組小鼠肝臟TNF-α、MCP-1和IL-6含量明顯下降(P0.05),IL-10含量升高明顯(P0.01)。7.Dex預(yù)處理后可以明顯改善肝臟組織的細(xì)胞凋亡情況:與sham相比較,IR組小鼠肝臟中Bcl-2蛋白表達(dá)量下降(P0.01),Bax和Caspase 3蛋白表達(dá)量升高(P0.01);與IR組相比較,25ug/kg Dex組小鼠肝臟中Bax蛋白表達(dá)量下降(P0.05),Caspase 3和Bcl-2蛋白表達(dá)下降不明顯(P0.05);50 ug/kg DEX、100 ug/kg Dex組小鼠肝臟中Bcl-2蛋白表達(dá)量升高(P0.05),Bax和Caspase 3蛋白表達(dá)量下降(P0.05)。結(jié)論1.腎臟缺血再灌注可導(dǎo)致肝臟損傷。2.DEX對(duì)腎臟IR導(dǎo)致肝臟損傷的保護(hù)作用可以通過(guò)提高肝臟抗氧化和抗凋亡能力來(lái)發(fā)揮的。3.50 ug/kg、100 ug/kg Dex預(yù)處理對(duì)腎臟IR導(dǎo)致的肝臟損傷的保護(hù)作用比較明顯。
[Abstract]:Objective to investigate the protective effect and mechanism of different doses of dexmedetomidine (DEX) preconditioning on liver injury induced by IRI in mice kidney. Method animal experiment: 40 healthy male C57 BL/6J mice of 8 weeks old were randomly divided into 5 groups: sham group, IRI group, 25 mu g/kg Dex group (low dose), 50 micron Dex group (middle dose) and 100 mu g/kg Dex group (Gao Jiliang), 8 rats in each group, 8 rats in each group. In addition to group sham, all the mice in the other groups were incisive in the bilateral renal region of the middle back of the back, with a blunt separation of the surrounding muscle tissue and the fascia of the kidney with a glass needle. The renal ischemia was caused by the unwound artery clamp and the renal ischemia was created by the unwound artery clamp. The mice were killed and the kidney and liver tissues were collected after the operation. The kidney and the liver tissues were collected and the kidney was collected to detect the kidney of the mice. The pathological changes of kidney and liver in mice were observed by HE staining. The activity of total superoxide dismutase (SOD) in liver tissues of mice was detected by WST-1. The content of malondialdehyde (MDA) in liver tissue of mice was measured by TBA, and the content of glutathione peroxidase (GSH-PX) in kidney tissue of mice was measured by colorimetry. The liver homogenization of mice was detected by ELISA method. The content of inflammatory factors TNF- alpha, MCP-1, IL-6, and anti-inflammatory factor IL-10 in the serous, and the Western-blot method to detect the expression of Caspase3, Bcl-2 and Bax protein in the liver tissues of mice. Results the renal function changes caused by IRI were obviously improved by 1.Dex pretreatment. Compared with group IR, the decrease of Bun in the plasma of 25ug/kg Dex group was not obvious (P0.05), and Scr and Cys-C decreased significantly (P0.05); 50 ug/kg, 100 ug/kg Dex group mice plasma The content of AST and ALT in plasma increased significantly (P0.01). Compared with the IR group, the levels of AST and ALT in the plasma of 25ug/kg Dex, 50 ug/kg and 100 ug/kg Dex mice were significantly decreased. Compared with the IR group, the renal lesions of the 25ug/kg Dex, 50 ug/kg Dex, and the 100 ug/kg Dex group were obviously improved by the improvement of.4.Dex preconditioning, and the pathological changes in the kidney caused by IRI were obviously improved. Compared with the sham phase, the IR group had obvious lesions, HE staining showed A large number of inflammatory cells in the liver of IR mice were infiltrated, the hepatic sinusoids dilated, a small amount of vacuoles formed and the liver cells were arranged in disorder. Compared with the IR group, 25ug/kg Dex, 50 ug/kg Dex, and the liver lesions of the 100 ug/kg Dex mice were obviously improved by the improvement of.5.Dex preconditioning, and the total antioxidant capacity in the liver was improved and the total antioxidant capacity in the tissues was improved. Compared with sham, the activity of SOD and the activity of GSH-PX in the liver of IR mice decreased significantly (P0.05), and the content of MDA increased significantly (P0.01). Compared with the IR group, 25ug/kg Dex, 50 ug/kg DEX, the activity and activity of the liver in the liver of the 100 mice were significantly increased. Compared with sham, the levels of TNF- alpha, IL-6, IL-10 and MCP-1 in the liver of IR mice increased (P0.05), and compared with those in the IR group, 25ug/kg Dex, 50 ug/kg, and the 100 ug/kg pretreated mice were significantly improved. The apoptosis of liver tissue: compared with sham, the expression of Bcl-2 protein in the liver of IR mice decreased (P0.01), and the expression of Bax and Caspase 3 protein increased (P0.01). Compared with the IR group, the expression of Bax protein in the liver of the 25ug/kg Dex group decreased (P0.05), and the decline of the 3 and the protein expression was not obvious; 50 The expression of Bcl-2 protein in the liver of /kg Dex mice increased (P0.05) and the expression of Bax and Caspase 3 protein decreased (P0.05). Conclusion 1. renal ischemia-reperfusion can lead to the protective effect of liver injury.2.DEX on kidney IR induced liver damage, which can be achieved by improving the liver antioxidant and anti withering ability of.3.50 ug/kg, 100 ug/kg. The protective effect of Li on liver injury caused by IR is obvious.
【學(xué)位授予單位】：錦州醫(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)】：R614

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 曾樂(lè);肝損傷的保守治療[J];中國(guó)急救醫(yī)學(xué);2002年05期

2 岳蘭竹;付蓉;阮二寶;梁勇;劉鴻;瞿文;宋嘉;關(guān)晶;王曉明;王國(guó)錦;王化泉;邢莉民;吳玉紅;王s，

本文編號(hào)：1938235