血小板生成素在D-氨基半乳糖诱导的急性肝衰竭模型中的作用

发布时间：2018-07-16 17:29

【摘要】：目的研究血小板生成素是否在D-氨基半乳糖诱导大鼠急性肝衰竭模型后减轻肝损伤。 方法雄性SD大鼠随机分为3组,分别为：对照组、模型组、TPO组。正常大鼠为对照组。于腹腔注射D-氨基半乳糖(剂量为1400mg/kg)诱导急性肝衰竭模型的大鼠为模型组。在诱导急性肝衰竭模型后,立即于尾静脉注射单次剂量的TPO(剂量为0.2μg/kg)的大鼠作为TPO组。对照组在D-氨基半乳糖注射后72h处死5只大鼠,模型组和TPO组在D-氨基半乳糖注射后12、24、48、72h各处死5只大鼠。通过肝组织病理学和血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和总胆红素(TBil)评估肝脏损伤程度。通过酶联免疫吸附试验(ELISA)检测血清肿瘤坏死因子-α(TNF-a)和白介素-6(IL-6)。通过免疫组织化学检测肝组织增殖细胞核抗原(PCNA)阳性细胞百分率和TNF-α。另外,模型组和TPO组各取10只大鼠观察D-氨基半乳糖注射后72h的生存率。 结果1.模型组和TPO组的血清ALT、 AST和TBil水平在D-氨基半乳糖注射后12h已升高,48h时达高峰。两组间在相同时间点无明显差异(P0.05)。2.ELISA显示模型组的IL-6浓度在D-氨基半乳糖注射后显著升高,在12h为32.37±4.67pg/ml,在72h达高峰(264.36±74.25pg/ml)。 TPO组的IL-6浓度在D-氨基半乳糖注射后略微升高,在12h为31.53±5.22pg/ml,在72h为42.90±6.07pg/ml。模型组在48和72h血清IL-6浓度显著高于TPO组(P0.05)。3. ELISA显示TPO组的TNF-a浓度在D-氨基半乳糖注射后显著升高,在12h为32.22±6.35pg/ml,72h达高峰(200.65±61.93pg/ml)。模型组的TNF-a浓度在D-氨基半乳糖注射后略微下降,在12h为30.80±4.33pg/ml,在72h为23.00±7.20pg/ml。 TPO组在48和72h TNF-α浓度显著高于模型组(P0.05)。免疫组织化学显示肝组织TNF-α的光密度在模型组和TPO组的趋势与ELISA结果相同。TPO组在24、48和72h TNF-a光密度显著高于模型组(P0.05)。4.免疫组织化学显示模型组的PCNA表达在D-氨基半乳糖注射后逐步增高,12h为21.60±2.67%,48h达高峰(63.79±9.75%),72h明显下降(16.74±3.92%)。TPO组的PCNA表达在12h为20.85±3.84%,48h达高峰(70.21±12.88%),在72h仍然保持高水平(66.49±12.88%)。TPO组在72h的PCNA阳性细胞百分率显著高于模型组(P0.05)。5.肝组织病理学显示模型组和TPO组的肝组织形态在D-氨基半乳糖注射后48h发生明显改变,包括肝小叶结构混乱,肝血窦和中央静脉淤血,炎症细胞浸润以及肝细胞坏死,在72h有所好转。TPO组在48和72h的肝损伤程度明显重于模型组。6.模型组在D-氨基半乳糖造模后72h的生存率是60%(生存个数比例为6/10),TPO组是20%(生存个数比例为2/10)(P0.05)。 结论TPO增加TNF-a的水平,加重D-氨基半乳糖诱导的急性肝衰竭模型大鼠的肝组织损伤程度。
[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- 伪 (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- 伪 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 卤4.67 PG / ml at 12 h and reached the peak at 72 h (264.36 卤74.25pg/ml). The concentration of IL-6 in TPO group increased slightly after injection of D-galactosamine (31.53 卤5.22 PG / ml at 12 h and 42.90 卤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 卤6.35pg / ml) at 72 h (200.65 卤61.93pg/ml). The concentration of TNF-a in model group decreased slightly after injection of D-galactosamine, which was 30.80 卤4.33pg / ml at 12 h and 23.00 卤7.20pg / ml at 72 h. The concentration of TNF- 伪 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- 伪 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 卤2.67) and reached the peak at 48h (63.79 卤9.75%). The expression of PCNA in TPO group decreased significantly (16.74 卤3.92%). The expression of PCNA in TPO group reached its peak at 12 h (20.85 卤3.8448 h) (70.21 卤12.88%), and maintained a high level at 72 h (66.49 卤12.88%). In TPO group, the expression of PCNA reached a peak at 72 h (66.49 卤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.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R575.3

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