發(fā)布時(shí)間：2018-06-18 13:34

  本文選題：重組人粒細(xì)胞集落刺激因子D-氨基半乳糖 + 急性肝衰竭�。� 參考：《天津醫(yī)科大學(xué)》2013年碩士論文

【摘要】：目的評價(jià)重組人粒細(xì)胞集落刺激因子(rhG-CSF)對于D-氨基半乳糖(D-GalN)誘導(dǎo)的急性肝衰竭大鼠的影響。 方法把雄性SD大鼠隨機(jī)分為正常對照組、肝衰模型組、rhG-CSF立即給藥組、rhG-CSF延遲給藥組。除正常對照組外,其余三組均腹腔內(nèi)注射D-GalN (1400mg/kg)建立大鼠急性肝衰竭模型。RhG-CSF立即給藥組于造模后2小時(shí)立即給予皮下注射rhG-CSF (50μg/kg), rhG-CSF延遲給藥組于造模后72小時(shí)給予皮下注射rhG-CSF (50μg/kg),以上兩組分別于造模后72小時(shí)、2小時(shí)各接受一次皮下注射生理鹽水。肝衰模型組于造模后2小時(shí)、72小時(shí)給予兩次皮下注射生理鹽水。為觀察rhG-CSF對急性肝衰竭大鼠不同時(shí)間點(diǎn)的影響,于造模后12、24、48、72、120小時(shí),分別處死肝衰模型組及rhG-CSF立即給藥組5只大鼠,取血檢測丙氨酸氨基轉(zhuǎn)移酶、總膽紅素、外周血白細(xì)胞,取肝組織做HE染色觀察肝臟病理變化,并應(yīng)用免疫組織化學(xué)方法測定PCNA陽性細(xì)胞、TNF-α陽性細(xì)胞；以上兩組均取10只大鼠觀察造模后120小時(shí)生存率。RhG-CSF延遲給藥組以皮下注射rhG-CSF為觀察始點(diǎn),以肝衰造模120小時(shí)為觀察終點(diǎn),并與肝衰模型組、rhG-CSF立即給藥組進(jìn)行比較。 結(jié)果肝臟病理結(jié)果顯示：RhG-CSF立即給藥組與肝衰模型組相比,除肝衰造模120小時(shí)外,其余各個(gè)時(shí)間點(diǎn)病理結(jié)果均顯示肝細(xì)胞壞死更為嚴(yán)重,同時(shí)伴有更為明顯的膽管再生；肝衰造模后120小時(shí)的病理結(jié)果顯示,rhG-CSF立即給藥組較肝衰模型組肝臟組織結(jié)構(gòu)恢復(fù)較好伴有更少的淋巴細(xì)胞浸潤,而rhG-CSF延遲給藥組其肝臟組織結(jié)構(gòu)恢復(fù)又明顯好于rhG-CSF立即給藥組。免疫組織化學(xué)方法結(jié)果顯示：RhG-CSF立即給藥組PCNA陽性細(xì)胞數(shù)、TNF-a陽性細(xì)胞數(shù)于各個(gè)時(shí)間點(diǎn),水平均明顯高于肝衰模型組;而rhG-CSF延遲給藥組于造模后120小時(shí),PCNA陽性細(xì)胞數(shù)明顯高于肝衰模型組,但相比于rhG-CSF立即給藥組無明顯差別,TNF-a陽性細(xì)胞數(shù)相比于肝衰模型組、rhG-CSF立即給藥組則均明顯減少。血清丙氨酸氨基轉(zhuǎn)移酶及總膽紅素水平結(jié)果顯示：RhG-CSF立即給藥組在肝衰造模后各個(gè)時(shí)間點(diǎn)其水平均高于肝衰模型組,但血清丙氨酸氨基轉(zhuǎn)移酶僅于造模后24小時(shí)兩組差異有統(tǒng)計(jì)學(xué)意義(P0.05),總膽紅素水平僅于造模后12,24小時(shí)差異有統(tǒng)計(jì)學(xué)意義(P0.05);RhG-CSF延遲給藥組于造模后120小時(shí),血清丙氨酸氨基轉(zhuǎn)移酶及總膽紅素水平與肝衰模型組及rhG-CSF立即給藥組相比差異均無統(tǒng)計(jì)學(xué)意義。外周血白細(xì)胞計(jì)數(shù)結(jié)果顯示：于造模后各個(gè)時(shí)間點(diǎn),rhG-CSF立即給藥組均高于肝衰模型組,除造模后12小時(shí)外,其余時(shí)間點(diǎn)差異均有統(tǒng)計(jì)學(xué)意義(P0.05)；RhG-CSF延遲給藥組于造模后120小時(shí),外周血白細(xì)胞計(jì)數(shù)明顯高于肝衰模型組,差異有統(tǒng)計(jì)學(xué)意義(P0.05),但與rhG-CSF立即給藥組相比,外周血白細(xì)胞計(jì)數(shù)較之減少,差異無統(tǒng)計(jì)學(xué)意義(P0.05)。RhG-CSF立即給藥組和肝衰模型組相比,生存率差異無統(tǒng)計(jì)學(xué)意義(30%,78.9+8.95小時(shí)VS20%,77.30±10.18小時(shí))；RhG-CSF延遲給藥組6只成功給予rhG-CSF大鼠中5只存活。 結(jié)論在ALF急性期應(yīng)用rhG-CSF加重肝臟炎癥反應(yīng)；在急性期過后應(yīng)用rhG-CSF促進(jìn)肝臟組織的修復(fù),降低炎癥反應(yīng),并有提高ALF生存率的可能,結(jié)果有待進(jìn)一步研究證實(shí)。
[Abstract]:Objective to evaluate the effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) on D- galactoside (D-GalN) - induced acute liver failure in rats.
Methods the male SD rats were randomly divided into the normal control group, the liver failure model group, the rhG-CSF immediate administration group and the rhG-CSF delayed administration group. Except the normal control group, the other three groups were intraperitoneally injected with D-GalN (1400mg/kg) to establish the rat acute hepatic failure model.RhG-CSF immediately given the subcutaneous injection of rhG-CSF (50 mu g/kg) immediately after the model. The rhG-CSF delayed injection group was given a subcutaneous injection of rhG-CSF (50 g/kg) 72 hours after the model, and the above two groups were given a subcutaneous injection of saline at 72 hours after making the model, and the liver failure model group was given two subcutaneous injection of saline after 72 hours after the model of the model, in order to observe the difference between the rhG-CSF and the rats with acute hepatic failure. At 12,24,48,72120 hours after the model, 5 rats were sacrificed to the liver failure model group and the rhG-CSF immediate administration group. The serum alanine aminotransferase, total bilirubin, peripheral blood leukocytes and liver tissue were detected by HE staining, and the pathological changes of the liver were observed by HE staining. The PCNA positive cells were detected by the immunoimmunoassay method, and the positive of TNF- alpha was positive. Cells in the above two groups were taken 10 rats to observe the 120 hour survival rate of.RhG-CSF delayed injection group by subcutaneous injection of rhG-CSF as the beginning point, with liver failure model for 120 hours as the observation end point, and compared with the liver failure model group, rhG-CSF immediate drug delivery group.
Results the liver pathological results showed that the RhG-CSF group was compared with the liver failure model group. Except for the liver failure model 120 hours, the pathological results of the other time points showed that the hepatocyte necrosis was more serious and accompanied by more obvious bile duct regeneration. The pathological results of the 120 hours after the liver failure model showed that the rhG-CSF immediate administration group was more than the liver failure. The liver tissue structure of the model group was well restored with less lymphocyte infiltration, and the liver tissue structure of the rhG-CSF delayed drug group was better than that of the rhG-CSF immediate administration group. The results of immunohistochemical staining showed that the number of PCNA positive cells in the group of RhG-CSF was immediately given, and the number of TNF-a positive cells was at every time point, and the level was obvious. The number of PCNA positive cells in the rhG-CSF delayed administration group was significantly higher than that in the liver failure model group at 120 hours after the model group, but the number of TNF-a positive cells was significantly lower than that in the rhG-CSF group. The serum alanine aminotransferase and total bilirubin were significantly reduced in the rhG-CSF group. The level results showed that the level of RhG-CSF immediately after the liver failure model was higher than that in the liver failure model group, but the serum alanine aminotransferase was statistically significant (P0.05) only 24 hours after the model (P0.05), and the total bilirubin level was statistically significant (P0.05) only after the model of the model (P0.05); RhG-CSF delayed administration. There was no significant difference in serum alanine aminotransferase and total bilirubin level between the liver failure model group and the rhG-CSF group at 120 hours after the model group. The results of the peripheral blood white blood cell count showed that the rhG-CSF immediate administration group was higher than the liver failure model group at each time point after the model building, except 12 hours after the model building. The time point difference was statistically significant (P0.05); the white blood cell count in peripheral blood was significantly higher than that in the liver failure model group at 120 hours after the RhG-CSF delayed delivery group, and the difference was statistically significant (P0.05), but compared with the immediate rhG-CSF group, the white blood cell count of the peripheral blood was less than that of the rhG-CSF group, and the difference was not statistically significant (P0.05).RhG-CSF immediately given the drug There was no significant difference in the survival rate between the group and the liver failure model group (30%, 78.9+8.95 hours VS20%, 77.30 + 10.18 hours), and 6 of the RhG-CSF delayed drug delivery groups were given 5 survival in the rhG-CSF rats.
Conclusion the use of rhG-CSF in the acute phase of ALF aggravates the liver inflammation, and the application of rhG-CSF to promote the repair of liver tissue, reduce the inflammatory response and improve the survival rate of ALF after the acute stage. The results need to be further confirmed.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R575.3

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