本文選題：脂肪源間充質(zhì)干細(xì)胞　切入點(diǎn)：c-KIT　出處：《新鄉(xiāng)醫(yī)學(xué)院》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：背景急性腎損傷(Acute kidney injury, AKI)是一種常見危急重癥。多種原因可造成AK_I,如重癥感染及藥物等。隨著診療技術(shù)水平的提高,AKI的病死率有所下降,但是在合并AKI重癥病人的病死率仍達(dá)65%。目前AKI的治療以腎臟替代治療為主。近年脂肪源間充質(zhì)干細(xì)胞(adipose-derived mesenchymal stem cells, ADMSCs)治療AKI成為腎臟病工作者研究熱點(diǎn)之一。研究表明ADMSCs具有治療AKI的作用,且其來源豐富、易于分離培養(yǎng)、免疫原性低、體外擴(kuò)增快等優(yōu)點(diǎn)。但其具體的治療機(jī)制仍不確切。 目的 1.通過觀察腎損傷標(biāo)志物,來判斷ADMSCs對急性腎損傷的治療作用。 2.通過測定相關(guān)因子來分析ADMSCs治療小鼠AKI可能的機(jī)制,以期為臨床應(yīng)用ADMSCs治療AKI提供有力的實(shí)驗(yàn)依據(jù)。 方法 1.30只雄性KM小鼠隨機(jī)分成3組,正常對照(normal control)組、模型組(model group)和治療組(treatment group),每組10只小鼠。 2.正常組不做任何干預(yù)措施,模型組、治療組分別腹腔注射順鉑,治療組于注射順鉑12小時(shí)后經(jīng)尾靜脈注射ADMSCs懸液5×105/0.5mL,模型組于注射順鉑12小時(shí)后經(jīng)尾靜脈注射等劑量的生理鹽水。 3.注射順鉑7天后處死小鼠,心臟取血,測定血清尿素氮(BUN)和血肌酐(Scr)值來評價(jià)腎功能情況；通過光學(xué)顯微鏡觀察小鼠腎組織病理形態(tài)改變；免疫組織化學(xué)(immunohistochemistry, IHC)法檢測中性粒細(xì)胞明膠酶相關(guān)脂質(zhì)運(yùn)載蛋白(NGAL)、干細(xì)胞因子受體(c-KIT)、及干細(xì)胞因子(SCF)。 結(jié)果 1.與模型組相比,治療組BUN、Scr和NGAL等腎損傷標(biāo)志物明顯下降,及腎小管壞死(acute tubular necrosis, ATN)評分顯著降低(P0.05)亦明顯下降。 2.與模型組相比,治療組腎組織中c-KIT、SCF表達(dá)明顯增加；與正常組相比,模型組腎組織中c-KIT、SCF表達(dá)亦有所增加(P0.05)。 結(jié)論 1.外源性ADMSCs可以有效促進(jìn)受損腎小管上皮細(xì)胞修復(fù)的作用； 2.在AKI模型中,外源性ADMSCs可能通過旁分泌或其自身分泌細(xì)胞因子SCF及c-KIT的方式,并且激活SCF/c-KIT信號傳導(dǎo)通路從而抑制腎小管上皮細(xì)胞凋亡并促進(jìn)殘余的腎小管上皮細(xì)胞分化、增殖,進(jìn)而起到保護(hù)腎臟作用。
[Abstract]:Background Acute kidney injury (AKI) is a common type of acute acute renal injury. It can be caused by a variety of causes, such as severe infection and drugs, etc. With the improvement of diagnostic and treatment techniques, the mortality of AKI has decreased. However, the mortality rate of severe patients with AKI is still 65%. At present, renal replacement therapy is the main treatment of AKI. Recently, adipose-derived mesenchymal stem cells (ADMSCs) treatment of adipose-derived mesenchymal stem cells (ADMSCs) has become one of the hotspots in the study of renal disease workers. Ming ADMSCs has the effect of treating AKI. Its source is rich, easy to isolate and culture, low immunogenicity, rapid expansion in vitro, but its specific treatment mechanism is still not accurate. Purpose. 1. To evaluate the therapeutic effect of ADMSCs on acute renal injury by observing the markers of renal injury. 2. The possible mechanism of ADMSCs in the treatment of AKI in mice was analyzed by measuring the relevant factors, in order to provide an effective experimental basis for the clinical application of ADMSCs in the treatment of AKI. Method. 1.Thirty male km mice were randomly divided into 3 groups, normal control group, model group (n = 10) and treatment group (n = 10). 2.The normal group did not do any intervention, the model group and the treatment group were intraperitoneally injected with cisplatin. In the treatment group, 5 脳 105% 0.5 mL ADMSCs suspension was injected through the tail vein 12 hours after the injection of cisplatin, while in the model group, the same dose of normal saline was injected through the tail vein 12 hours after the injection of cisplatin. 3. The mice were sacrificed 7 days after injection of cisplatin, the blood was taken from the heart, the serum urea nitrogen (bun) and serum creatinine (SCR) were measured to evaluate the renal function, and the pathological changes of renal tissue were observed by optical microscope. Immunohistochemical method was used to detect neutrophil gelatinase-associated lipid carrier protein (NGALN), stem cell factor receptor c-KITT, and stem cell factor (SCF). Results. 1. Compared with the model group, the renal injury markers such as bun SCR and NGAL in the treatment group were significantly decreased, and the acute tubular necrosis (ATN) score in the treatment group was significantly lower than that in the control group (P 0.05). 2.Compared with the model group, the expression of c-KIT-SCF in the renal tissue of the treatment group was significantly increased, and the expression of c-KIT-SCF in the renal tissue of the model group was also increased compared with the normal group. Conclusion. 1. Exogenous ADMSCs can effectively promote the repair of damaged renal tubular epithelial cells; 2. In AKI model, exogenous ADMSCs may inhibit the apoptosis of renal tubular epithelial cells and promote the differentiation of residual tubular epithelial cells by paracrine or autocrine cytokines SCF and c-KIT, and activate the SCF/c-KIT signal transduction pathway. Proliferation, which in turn plays a role in protecting the kidney.
【學(xué)位授予單位】：新鄉(xiāng)醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R692.5

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