【摘要】：目的研究血小板生成素是否在D-氨基半乳糖誘導(dǎo)大鼠急性肝衰竭模型后減輕肝損傷。 方法雄性SD大鼠隨機(jī)分為3組,分別為：對照組、模型組、TPO組。正常大鼠為對照組。于腹腔注射D-氨基半乳糖(劑量為1400mg/kg)誘導(dǎo)急性肝衰竭模型的大鼠為模型組。在誘導(dǎo)急性肝衰竭模型后,立即于尾靜脈注射單次劑量的TPO(劑量為0.2μg/kg)的大鼠作為TPO組。對照組在D-氨基半乳糖注射后72h處死5只大鼠,模型組和TPO組在D-氨基半乳糖注射后12、24、48、72h各處死5只大鼠。通過肝組織病理學(xué)和血清丙氨酸轉(zhuǎn)氨酶(ALT)、天冬氨酸轉(zhuǎn)氨酶(AST)和總膽紅素(TBil)評估肝臟損傷程度。通過酶聯(lián)免疫吸附試驗(yàn)(ELISA)檢測血清腫瘤壞死因子-α(TNF-a)和白介素-6(IL-6)。通過免疫組織化學(xué)檢測肝組織增殖細(xì)胞核抗原(PCNA)陽性細(xì)胞百分率和TNF-α。另外,模型組和TPO組各取10只大鼠觀察D-氨基半乳糖注射后72h的生存率。 結(jié)果1.模型組和TPO組的血清ALT、 AST和TBil水平在D-氨基半乳糖注射后12h已升高,48h時(shí)達(dá)高峰。兩組間在相同時(shí)間點(diǎn)無明顯差異(P0.05)。2.ELISA顯示模型組的IL-6濃度在D-氨基半乳糖注射后顯著升高,在12h為32.37±4.67pg/ml,在72h達(dá)高峰(264.36±74.25pg/ml)。 TPO組的IL-6濃度在D-氨基半乳糖注射后略微升高,在12h為31.53±5.22pg/ml,在72h為42.90±6.07pg/ml。模型組在48和72h血清IL-6濃度顯著高于TPO組(P0.05)。3. ELISA顯示TPO組的TNF-a濃度在D-氨基半乳糖注射后顯著升高,在12h為32.22±6.35pg/ml,72h達(dá)高峰(200.65±61.93pg/ml)。模型組的TNF-a濃度在D-氨基半乳糖注射后略微下降,在12h為30.80±4.33pg/ml,在72h為23.00±7.20pg/ml。 TPO組在48和72h TNF-α濃度顯著高于模型組(P0.05)。免疫組織化學(xué)顯示肝組織TNF-α的光密度在模型組和TPO組的趨勢與ELISA結(jié)果相同。TPO組在24、48和72h TNF-a光密度顯著高于模型組(P0.05)。4.免疫組織化學(xué)顯示模型組的PCNA表達(dá)在D-氨基半乳糖注射后逐步增高,12h為21.60±2.67%,48h達(dá)高峰(63.79±9.75%),72h明顯下降(16.74±3.92%)。TPO組的PCNA表達(dá)在12h為20.85±3.84%,48h達(dá)高峰(70.21±12.88%),在72h仍然保持高水平(66.49±12.88%)。TPO組在72h的PCNA陽性細(xì)胞百分率顯著高于模型組(P0.05)。5.肝組織病理學(xué)顯示模型組和TPO組的肝組織形態(tài)在D-氨基半乳糖注射后48h發(fā)生明顯改變,包括肝小葉結(jié)構(gòu)混亂,肝血竇和中央靜脈淤血,炎癥細(xì)胞浸潤以及肝細(xì)胞壞死,在72h有所好轉(zhuǎn)。TPO組在48和72h的肝損傷程度明顯重于模型組。6.模型組在D-氨基半乳糖造模后72h的生存率是60%(生存?zhèn)�數(shù)比例為6/10),TPO組是20%(生存?zhèn)�數(shù)比例為2/10)(P0.05)。 結(jié)論TPO增加TNF-a的水平,加重D-氨基半乳糖誘導(dǎo)的急性肝衰竭模型大鼠的肝組織損傷程度。
[Abstract]:Aim to investigate whether thrombopoietin alleviates liver injury in rats with acute hepatic failure induced by D-galactosamine. Methods male SD rats were randomly divided into three groups: control group and model group. Normal rats served as control group. Rats with acute hepatic failure were induced by intraperitoneal injection of D-galactosamine (1400mg/kg) as model group. After the acute hepatic failure model was induced, rats with a single dose of TPO (0.2 渭 g/kg) were injected into the tail vein immediately as the TPO group. In the control group, 5 rats were killed at 72 h after injection of D-galactosamine, and 5 rats in the model group and TPO group died at 72 h after injection of D-galactosamine. Liver injury was assessed by liver histopathology, serum alanine aminotransferase (alt), aspartate aminotransferase (AST) and total bilirubin (TBil). Serum tumor necrosis factor- 偽 (TNF-a) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (Elisa). The percentage of proliferating cell nuclear antigen (PCNA) positive cells and TNF- 偽 were detected by immunohistochemistry. In addition, 10 rats in the model group and 10 in the TPO group were taken to observe the 72 h survival rate after D-galactosamine injection. Result 1. The serum levels of alt, AST and TBil in model group and TPO group reached the peak at 12 h after injection of D-galactosamine. There was no significant difference between the two groups at the same time point (P0.05). 2. Elisa showed that the concentration of IL-6 in the model group increased significantly after injection of D-galactosamine, which was 32.37 鹵4.67 PG / ml at 12 h and reached the peak at 72 h (264.36 鹵74.25pg/ml). The concentration of IL-6 in TPO group increased slightly after injection of D-galactosamine (31.53 鹵5.22 PG / ml at 12 h and 42.90 鹵6.07 pg / ml at 72 h). Serum IL-6 levels in the model group were significantly higher than those in the TPO group at 48 and 72 h (P0.05). Elisa showed that the concentration of TNF-a in TPO group increased significantly after injection of D-galactosamine, and reached its peak at 12 h (32.22 鹵6.35pg / ml) at 72 h (200.65 鹵61.93pg/ml). The concentration of TNF-a in model group decreased slightly after injection of D-galactosamine, which was 30.80 鹵4.33pg / ml at 12 h and 23.00 鹵7.20pg / ml at 72 h. The concentration of TNF- 偽 in TPO group was significantly higher than that in model group at 48 and 72 h (P0.05). Immunohistochemistry showed that the optical density of TNF- 偽 in the model group and TPO group was the same as that in the Elisa group. The optical density of TNF-a in the TPO group was significantly higher than that in the model group at 24: 48 and 72 h (P0.05). Immunohistochemistry showed that the expression of PCNA in model group was gradually increased at 12 h after injection of D-galactosamine (21.60 鹵2.67) and reached the peak at 48h (63.79 鹵9.75%). The expression of PCNA in TPO group decreased significantly (16.74 鹵3.92%). The expression of PCNA in TPO group reached its peak at 12 h (20.85 鹵3.8448 h) (70.21 鹵12.88%), and maintained a high level at 72 h (66.49 鹵12.88%). In TPO group, the expression of PCNA reached a peak at 72 h (66.49 鹵12.88%). The percentage of sex cells in the model group was significantly higher than that in the model group (P0.05). Liver histopathology showed that the liver histomorphology of model group and TPO group changed significantly 48 hours after injection of D-galactosamine, including hepatic lobule structure disorder, hepatic sinusoidal and central vein congestion, inflammatory cell infiltration and hepatocyte necrosis. At 72 h, the degree of liver injury in TPO group was significantly more serious than that in model group at 48 and 72 hours. The survival rate of the model group after D-galactosamine was 60% (6 / 10) and 20% (2 / 10) in the TPO group (P0.05). Conclusion TPO can increase the level of TNF-a and aggravate the degree of liver tissue damage induced by D-galactosamine in rats with acute hepatic failure.
【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

【共引文獻(xiàn)】

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