發(fā)布時(shí)間：2018-06-16 06:12

  本文選題：地塞米松 + 孕激素��； 參考：《新鄉(xiāng)醫(yī)學(xué)院》2017年碩士論文

【摘要】：背景妊娠期肝內(nèi)膽汁淤積癥(Intrahepatic Cholestasis of Pregnancy,ICP)是孕期發(fā)生的一種臨床綜合癥,如:孕婦肝損傷出現(xiàn),肝酶升高,總膽酸異常,胎兒、新生兒缺氧死亡發(fā)生等。既往研究表明該病可誘使復(fù)雜的膽汁酸基因調(diào)控網(wǎng)絡(luò)發(fā)生異常,繼發(fā)圍產(chǎn)兒不良預(yù)后結(jié)局出現(xiàn),并且通過(guò)現(xiàn)有臨床技術(shù)手段難以提前預(yù)測(cè),找到一種較好的治療方法或安全有效的預(yù)防方式是產(chǎn)科有待解決的一大難題。目的探討法尼醇受體(Farnesoid X receptor,FXR)/膽鹽輸出泵(Bile salt export pump,BSEP)對(duì)孕激素誘導(dǎo)的妊娠期SD大鼠肝內(nèi)膽汁淤積癥的調(diào)控作用及地塞米松的干預(yù)機(jī)制。方法選擇清潔級(jí)SD孕鼠45只,隨機(jī)區(qū)組分成3組(陰性對(duì)照組:對(duì)照組;陽(yáng)性對(duì)照組:模型組;治療組),每組15只,妊娠第10-14天,每天腹腔注射1次:對(duì)照組生理鹽水2.5ml/kg/d;模型組及治療組注射孕酮225mg/kg/d建立動(dòng)物模型。各組孕鼠于妊娠第10天及第15天分別采心臟血2ml,測(cè)定血生化指標(biāo)。治療組造模成功后于妊娠d15-19天,每天1次大腿內(nèi)側(cè)肌肉注射地塞米松1mg/kg,妊娠第20天采集心臟血2mL備用。3組孕鼠出現(xiàn)臨產(chǎn)征兆時(shí)立即行剖宮終止妊娠,記錄胎鼠數(shù),死胎數(shù),測(cè)量胎鼠體重;取孕鼠肝臟組織觀察病理學(xué)變化,采用逆轉(zhuǎn)錄聚合酶鏈反應(yīng)技術(shù)檢測(cè)FXR、BSEP兩者mRNA的表達(dá),蛋白質(zhì)印跡法檢測(cè)兩者蛋白的表達(dá)。結(jié)果(1)各組孕鼠血生化指標(biāo)用藥前差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),模型組用藥后血清總膽酸(Total bile acid,TBA)及谷丙轉(zhuǎn)氨酶(Alanine aminotransferase,ALT)明顯升高(P0.05),地塞米松干預(yù)前后比較,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。(2)HE染色:模型組孕鼠匯管區(qū)肝細(xì)胞出現(xiàn)水腫,肝血竇間隙變窄,少許肝細(xì)胞出現(xiàn)脂肪變性;治療組孕鼠肝細(xì)胞排列整齊無(wú)明顯水腫,無(wú)脂肪變性,肝血竇間隙正常。(3)死胎率比較:模型組顯著高于對(duì)照組,治療組顯著低于模型組(P0.05)。(4)各組胎鼠體重比較:模型組明顯低于對(duì)照組和治療組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。(5)模型組孕鼠肝臟中FXR、FXRmRNA的表達(dá)上調(diào),BSEP、BSEPmRNA的表達(dá)下調(diào)(P0.05);治療組與模型組比較孕鼠肝臟中FXR、FXRmRNA表達(dá)下調(diào),BSEP、BSEPmRNA的表達(dá)上調(diào)(P0.05)。結(jié)論地塞米松干預(yù)ICP的調(diào)控機(jī)制可能是通過(guò)減少了妊娠大鼠肝臟FXR的表達(dá),上調(diào)BSEP的表達(dá),降低了機(jī)體對(duì)孕激素及其代謝產(chǎn)物的敏感性,從而對(duì)膽汁淤積孕鼠的肝臟功能起到了保護(hù)作用,并有效減少胎鼠不良預(yù)后的出現(xiàn)。
[Abstract]:Intrahepatic Cholestasis of Pregnancy (ICP) is a clinical syndrome occurring during pregnancy, such as the occurrence of liver injury in pregnant women, the increase of liver enzyme, the abnormal total cholic acid, fetal and neonatal hypoxia death. Previous studies have shown that the disease can induce the complex bile acid gene regulation network to occur abnormality. Poor prognosis of perinatal fetus appears, and it is difficult to predict in advance through existing clinical techniques. Finding a better treatment method or safe and effective prevention is a major problem to be solved in obstetrics. The purpose of this study is to explore the Farnesoid X receptor (FXR) / bile salt output pump (Bile salt export pump, BSEP) for pregnancy The regulation of intrahepatic cholestasis of SD rats and the intervention mechanism of dexamethasone. Methods 45 clean SD pregnant rats were selected and divided into 3 groups (negative control group: control group; positive control group: model group; treatment group), 15 rats in each group, 10-14 days of pregnancy, 1 times per day: saline 2.5ml/kg in control group. /d, the model group and the treatment group were injected with progesterone 225mg/kg/d to establish an animal model. Each group of pregnant rats took the heart blood 2ml for the tenth and 15 days of pregnancy, respectively, and measured the blood biochemical indexes. After the success of the treatment group, 1 times every day, 1 times the medial thigh muscles were injected with dexamethasone 1mg/kg, and the 2mL spare.3 group of the heart blood was collected for twentieth days of pregnancy. The gestational termination of pregnancy was performed immediately, the number of fetal rats, the number of stillbirths, the weight of fetal rats were recorded, the pathological changes of the liver tissues of pregnant rats were observed. The expression of FXR, BSEP mRNA were detected by reverse transcription polymerase chain reaction (RT), and the expression of egg white was detected by Western blot. Results (1) the blood biochemical indexes of pregnant rats were used before drug use. The difference was not statistically significant (P0.05). The serum total cholic acid (Total bile acid, TBA) and alanine transaminase (Alanine aminotransferase, ALT) in the model group were significantly increased (P0.05). The difference was statistically significant (P0.05) before and after the intervention of dexamethasone. (2) HE staining: the liver cells of the model group of pregnant rats were edema and the hepatic sinusoidal space narrowed, In the treatment group, the liver cells in the treatment group had no obvious edema, no fat degeneration, and the hepatic sinusoidal space was normal. (3) the rate of stillbirth was compared: the model group was significantly higher than the control group, and the treatment group was significantly lower than the model group (P0.05). (4) the weight comparison of the mice in each group was significantly lower than the control group and the treatment group, the difference was statistically significant. (5) (5) the expression of FXR, FXRmRNA, BSEP and BSEPmRNA was down regulated in the liver of the model group, and the expression of FXR, FXRmRNA, BSEP and BSEPmRNA in the liver of the pregnant rats was down regulated (P0.05) in the treatment group. Expression, up - regulation the expression of BSEP, reduce the body's sensitivity to progestin and its metabolites, thus protecting the liver function of gestation rats, and effectively reducing the occurrence of bad prognosis in fetal mice.
【學(xué)位授予單位】：新鄉(xiāng)醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R714.255

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