【摘要】：背景:研究表明臍帶間充質(zhì)干細胞可以顯著改善肝硬化的程度,進而修復(fù)肝損傷,但其治療肝硬化的分子調(diào)控機制,尤其是非編碼RNA調(diào)控的肝內(nèi)基因變化,目前并沒有得到詳細的闡釋。目的:分析人臍帶間充質(zhì)干細胞移植肝硬化大鼠肝細胞中微小RNA基因表達的變化。方法:采用四氯化碳皮下注射聯(lián)合乙醇喂服方法建立肝硬化大鼠模型,造模8周后經(jīng)尾靜脈輸注人臍帶間充質(zhì)干細胞,每周1次,連續(xù)注射4周。最后一次注射治療1周后收集大鼠肝臟組織進行石蠟切片和提取肝臟RNA進行表達譜基因芯片分析,同時收集血清利用自動生化分析儀測定肝功能指標變化。結(jié)果與結(jié)論:人臍帶間充質(zhì)干細胞治療可以顯著降低谷丙轉(zhuǎn)氨酶、谷草轉(zhuǎn)氨酶和轉(zhuǎn)肽酶水平,脂肪病變和肝細胞壞死顯著減少。微小RNA表達譜芯片雜交分析和PCR驗證結(jié)果顯示rno-mi R-369-5p、rno-mi R-3584-5p和rno-mi R-153*這3種微小RNA基因在造模過程中先下調(diào)表達,并在人臍帶間充質(zhì)干細胞治療后顯著上調(diào);而rno-mi R-93、rno-mi R-199a-3p、rno-mi R-195、rno-let-7a和rno-mi R-19a這5種微小RNA基因在造模過程中先上調(diào)表達,并在人臍帶間充質(zhì)干細胞治療后顯著下調(diào)。以上結(jié)果表明人臍帶間充質(zhì)干細胞逆轉(zhuǎn)肝硬化和肝細胞損傷過程中,可能通過上調(diào)rno-miR-369-5p、rno-mi R-3584-5p和rno-mi R-153*等miR NA基因表達,下調(diào)rno-miR-93、rno-mi R-199a-3p、rno-mi R-195、rno-let-7a和rno-mi R-19a等相關(guān)miR NA基因表達發(fā)揮治療作用。
[Abstract]:Background: studies have shown that umbilical cord mesenchymal stem cells can significantly improve the degree of liver cirrhosis and repair liver injury, but its treatment of liver cirrhosis molecular regulatory mechanism, especially the non-coding RNA regulation of intrahepatic gene changes. At present, there is no detailed explanation. Aim: to investigate the changes of RNA gene expression in hepatocytes of cirrhotic rats transplanted with human umbilical cord mesenchymal stem cells. Methods: the rat model of liver cirrhosis was established by subcutaneous injection of carbon tetrachloride (CCL 4) combined with ethanol administration. After 8 weeks, human umbilical cord mesenchymal stem cells were infused via tail vein once a week for 4 weeks. One week after the last injection, the rat liver tissue was collected for paraffin section, RNA was extracted for gene chip analysis, and the serum was collected to determine the changes of liver function by automatic biochemistry analyzer. Results and conclusion: human umbilical cord mesenchymal stem cell therapy can significantly reduce the levels of alanine aminotransferase, alanine aminotransferase and transpeptidase, fatty lesions and hepatocyte necrosis. The results of microarray hybridization and PCR verification showed that rno-mi R-369-5pno-mi R-3584-5p and rno-mi R-153* were down-regulated in the process of modeling, and the results of microarray hybridization and PCR verification showed that the expression of rno-mi R-369-5pno-mi R-3584-5p and rno-mi R-153* were down-regulated. It was significantly up-regulated after treatment with human umbilical cord mesenchymal stem cells. However, rno-mi R-93rno-mi R-199a-3pnrno-mi R-195 rno-let-7a and rno-mi R-19a up-regulated the expression of RNA genes during the modeling process, and down-regulated significantly after treatment with human umbilical cord mesenchymal stem cells. These results suggest that human umbilical cord mesenchymal stem cells may down-regulate rno-miR-93, by up-regulating the expression of miR NA genes such as rno-miR-369-5p,rno-mi R-3584-5p and rno-mi R-153* in the process of reversing liver cirrhosis and hepatocyte damage. The expression of miR NA genes such as rno-mi R-199a-3pno-mi R-195rno-let-7a and rno-mi R-19a plays a therapeutic role.
【作者單位】： 煙臺市傳染病醫(yī)院;北京大學(xué)第一醫(yī)院;山東大學(xué)齊魯醫(yī)院;
【基金】：濟南市2014科學(xué)技術(shù)發(fā)展計劃(201403010)~~
【分類號】：R575.2

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