脂多糖预处理减轻对乙酰氨基酚所致急性肝损伤

发布时间：2018-06-22 06:52

本文选题：脂多糖 + 对乙酰氨基酚　；参考：《安徽医科大学》2014年硕士论文

【摘要】：目的乙酰氨基酚(Acetaminophen,APAP)是常用的非甾体类解热镇痛药,过量APAP会导致急性肝损伤。脂多糖(lipopolysaccharides,LPS)是革兰氏阴性杆菌细胞壁的主要组分之一,低剂量的LPS能够活化单核巨噬细胞系统,对特异性免疫反应具有调节作用。本课题拟在建立APAP引起小鼠急性肝损伤动物模型的基础上,探讨低剂量LPS预处理对APAP引起急性肝损伤的影响。方法(1)为观察LPS对APAP所致小鼠急性肝损伤存活率的影响,选取ICR雄性小鼠20只,随机分成APAP组和LPS+APAP组。禁食10h后,APAP组腹腔注射APAP(300mg/kg);LPS+APAP组经腹腔注射先给予LPS(50μg/kg),3h后再给予APAP(300mg/kg)。密切观察小鼠存活状况,72h后取材,测生化指标、HE染色。(2)为探讨LPS对小鼠APAP急性肝损伤保护作用发生与发展的时间过程,ICR雄性小鼠随机分成APAP 0h,0.5h,6h,12h,24h,72h组和LPS+APAP 0h,0.5h,6h,12h,24h,72h组,每组6只。禁食后,APAP组腹腔注射APAP(300mg/kg);LPS+APAP组腹腔注射LPS(50μg/kg),3h后再经腹腔注射APAP(300mg/kg)。分别在每组对应时点(0h,0.5h,6h,12h,24h,72h)取材。分离血清用于生化检测,取部分肝组织用于病理检查。结果(1)APAP组给药4h左右小鼠开始出现死亡情况,72h存活率为50%;LPS+APAP联合处理组,72h内无死亡。(2)随着药物作用时间的延长,APAP组小鼠的肝脏系数(肝重/体重×100%)、血清ALT值逐渐升高,在24h时点达到最高值,与对照组(APAP 0h)相比,有统计学差异。LPS+APAP组与对照组相比,小鼠肝脏系数都有一定程度的增加,在0.5h时点达到最高,之后逐渐降低;与APAP组12h、24h时点进行比较,小鼠的肝脏系数低于APAP12h、24h时点(P0.05)。LPS+APAP组ALT值逐渐增高,但升高幅度显著低于APAP组。(3)给药后,随着APAP作用时间的延长,肝脏损伤情况进行性加重,坏死面积占比不断增高。24h时点,坏死面积占比65.64%。LPS+APAP组肝脏受损情况明显改善,24h坏死面积占比为28.44%,两者间有显著性差异(P0.01)。(4)LPS+APAP组0h时点GSH含量为0.90±0.15μmol/g,对照组为0.92±0.20μmol/g,两者间没有统计学差异。0.5h时,APAP组0.36μmol/g,LPS+APAP组0.37μmol/g。结论低剂量LPS预处理能减轻对乙酰氨基酚所致急性肝损伤,具体机制尚不明确。低剂量LPS预处理产生的这种效应可能与其激活了机体的免疫应答,抑制了GSH耗竭的下游机制有关。
[Abstract]:Objective Acetaminophenol (APAP) is a common non-steroidal antipyretic analgesics. Excessive APAP can lead to acute liver injury. Lipopolysaccharide (LPS) is a major component of the cell wall of Gram-negative bacilli (Gram-negative bacilli). Low dose LPS can activate the mononuclear macrophage system and regulate the specific immune response. Based on the animal model of acute liver injury induced by APAP in mice, the effect of low dose LPS preconditioning on acute liver injury induced by APAP was studied. Methods (1) to observe the effect of LPS on the survival rate of acute liver injury induced by APAP, 20 ICR male mice were randomly divided into APAP group and LPS APAP group. After fasting for 10 h, APAP group was intraperitoneally injected with 300mg/kg and LPS-APAP group was given LPS-50 渭 g/kg for 3 h and then 300mg/kg. The survival status of mice was observed 72 hours later and the biochemical indexes were determined by HE staining. (2) in order to investigate the time course of the occurrence and development of acute hepatic injury induced by LPS in mice, ICR male mice were randomly divided into two groups: APAP 0 h 0 h, 0. 5 h, 12 h, 24 h, 72 h, and LPS 0 h, 0. 5 h, 6 h, 12 h, 24 h, 72 h, each group consisted of 6 rats. After fasting, APAP group was intraperitoneally injected with 300mg/kg (50 渭 g/kg) and then 300mg/kg was injected intraperitoneally for 3 h. The samples were collected at the corresponding time points (0 h, 0.5 h, 6 h, 12 h, 24 h, 72 h) in each group. The isolated serum was used for biochemical examination and some liver tissues were taken for pathological examination. Results (1) in APAP group, there was no death within 72 hours after treatment with LPS-APAP. (2) the liver coefficient (liver weight / body weight 脳 100%) of mice in APAP group increased gradually with the prolongation of the time of administration of APAP. Compared with the control group (APAP 0 h), the liver coefficient of LPS APAP group increased to a certain extent, reached the highest at 0.5 h, and then decreased gradually. Compared with APAP group at 12h and 24h, the liver coefficient of mice was lower than that of APAP 12h or 24h (P0.05). The alt value of LPS APAP group gradually increased, but the increase range was significantly lower than that of APAP group. (3) after administration of APAP, the liver injury gradually aggravated with the prolongation of APAP action time. The percentage of necrotic area increased continuously. There was a significant difference between the two groups (P0.01). (_ 4). The content of GSH was 0.90 卤0.15 渭 mol / g at 0 h in LPS-APAP group and 0.92 卤0.20 渭 mol / g in control group. There was no statistical difference between the two groups at 0.5 h. There was no statistical difference between the two groups at 0.36 渭 mol 路mol / g, 0.37 渭 mol / g in APAP group. Conclusion low dose LPS preconditioning can attenuate acute hepatic injury induced by acetaminophen, and the mechanism is unclear. The effect of low dose LPS preconditioning may be related to its activation of immune response and inhibition of the downstream mechanism of GSH depletion.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R575

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