| 江 帆,王茂娟,张 练,谢 红,张 娟.不同剂量乌司他汀对急性重症胆管炎大鼠肝屏障的保护作用[J].,2018,(9):1664-1668 |
| 不同剂量乌司他汀对急性重症胆管炎大鼠肝屏障的保护作用 |
| Protective Effects of Different Dosage of Ulinastatin on Hepatic Barrier in Rats with Acute Cholangitis of Severe Type |
| 投稿时间：2017-08-12 修订日期：2017-08-31 |
| DOI：10.13241/j.cnki.pmb.2018.09.013 |
| 中文关键词: 急性重症胆管炎 大鼠 肝屏障 乌司他汀 |
| 英文关键词: ACST Rat Hepatic barrier Ulinastatin |
| 基金项目:四川省自然科学基金资助项目（2015120999） |
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| 中文摘要: |
| 摘要 目的：探讨不同剂量乌司他汀对急性重症胆管炎（ACST）大鼠肝屏障的保护作用。方法：60只雄性SD大鼠通过手术造成胆总管梗阻并注射细菌内毒素造成ACST模型，造模48 h后处死，随机分成5组，每组12只，分别进行假手术（SN组）、ACST造模手术（ACST组）、ACST造模手术+乌司他汀治疗，依据乌司他汀浓度分为低（20000 U/kg?d）（ASCT-L组）、中（40000 U/kg?d）（ASCT-M组）、高（80000 U/kg?d）（ASCT-H组）三组，采集血液进行总胆红素（TB）、谷丙转氨酶（ALT）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）和肿瘤坏死因子-α（TNF-α）的检测，采集部分肝组织进行组织染色，检测肝细胞凋亡率并分析紧密连接蛋白Occludin和ZO-1基因表达水平。结果：与SN组比较，造模后各组大鼠TB和ALT水平均显著升高（均P<0.05），乌司他汀治疗后各组大鼠TB和ALT水平随剂量增加而明显降低，各组间差异均有统计学意义（均P<0.05）；造模后大鼠IL-6、IL-10和TNF-α水平均显著升高，乌司他汀治疗后各组大鼠IL-6和TNF-α水平随剂量增加而降低，IL-10水平随剂量增加而升高，不同剂量间差异有统计学意义（均P<0.05）；ACST组肝细胞凋亡率显著高于SN组，Occludin和ZO-1基因表达水平显著降低（P<0.05）；乌司他汀治疗后各组大鼠肝细胞凋亡率有不同程度的降低，Occludin和ZO-1基因表达水平有不同程度的升高（P<0.05）。结论：乌司他汀治疗ACST大鼠疗效显著，对肝屏障功能有良好的保护作用，其治疗效果与剂量呈现明显的相关性，其机制及合适的给药剂量值得进一步研究。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the protective effects of different dosage of Ulinastatin on hepatic barrier in rats with acute cholangitis of severe type(ACST). Methods: A total of 60 male SD rats were induced by operation to cause the common bile duct ob- struction and were injected with endotoxin for the ACST model. All the rats were killed 48 hours after model operation and were ran- domly divided into five groups with 12 rats in each group, and were treated with sham operation (SN group), ACST model operation (ACST group)and ACST model operation+Ulinastatin respectively. According to the dosage of Ulinastatin, the rats were divided into low solution(20000 U/kg?d)(ASCT-L group), middle solution(40000 U/kg?d)(ASCT-M group) and high solution(80000 U/kg?d) (ASCT-H group) respectively. Blood was collected and the levels of total bilirubin(TB), alanine transaminase (ALT), interleukin-6 (IL-6), inter- leukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) were detected. Some hepatic tissues were collected for histological staining, the apoptosis rate of hepatocytes was detected and the expression levels of tight junction proteins Occludin and ZO-1 gene were analyzed. Results: Compared with SN group, the indexes of TB and ALT in the rats of each group after model operation were significantly in- creased (P<0.05). After treatment with Ulinastatin, the levels of TB and ALT in the rats of each group were significantly decreased with the increase of dosage, the differences were statistically significant between the groups (all P<0.05). The levels of IL-6, IL-10 and TNF-α were significantly higher in the rats after model operation. After treatment with Ulinastatin, the levels of IL-6 and TNF-α were decreased with the increase of dosage, while the levels of IL-10 were increased with the decrease of dosage, the differences were statistically sig- nificant between different dosage (all P<0.05). The apoptosis rate of hepatocytes in ACST group was significantly higher than that in SN group, the gene expression levels of Occludin and ZO-1 were decreased significantly(P<0.05). After treatment, the apoptosis rates of rats in each group were decreased in different degrees, the gene expression levels of Occludin and ZO-1 were increased in differ- ent degrees(P<0.05). Conclusion: Ulinastatin has significant effect in the treatment of ACST rats, and has good protective effect on hepatic barrier function. The treatment effect and dosage showed obvious correlation. Its mechanism and the appropriate dosage are worthy of further study. |
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