芬戈莫德对肾缺血再灌注损伤模型小鼠的肾保护作用及其机制研究
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篇名: 芬戈莫德对肾缺血再灌注损伤模型小鼠的肾保护作用及其机制研究
TITLE:
摘要: 目的:研究芬戈莫德对肾缺血再灌注损伤(RIRI)模型小鼠的肾保护作用及其机制。方法:将60只小鼠随机分为假手术组、模型组、芬戈莫德组(1 mg/kg)和芬戈莫德+wortmannin组[芬戈莫德1 mg/kg+磷脂酰肌醇3-激酶(PI3K)特异性阻滞药wortmannin 1.4 mg/kg],每组15只。除假手术组外,其余3组小鼠均建立RIRI模型,术前24 h一次性经尾静脉注射相应的药物。再灌注24 h后收集每组小鼠血清,使用全自动生化分析仪测量各组小鼠血清中血肌酐(Scr)和尿素氮(BUN)水平;光镜下观察肾组织病理变化;Western blot法检测肾组织中细胞间黏附分子1(ICAM-1)、单核细胞趋化蛋白1(MCP-1)、磷酸化蛋白激酶B(p-Akt)蛋白的表达。结果:与假手术组比较,模型组小鼠血清中Scr和BUN水平明显升高(P<0.01);肾组织出现病理性改变,肾小管上皮细胞坏死,炎性细胞浸润;肾组织中ICAM-1和MCP-1蛋白表达水平明显升高(P<0.01),p-Akt蛋白表达水平轻微升高(P>0.05)。与模型组比较,芬戈莫德组小鼠除肾组织中p-Akt蛋白表达水平明显升高(P<0.01)外,其余指标均明显改善(P<0.01)。与芬戈莫德组比较,芬戈莫德+wortmannin组小鼠的上述指标变化均逆转(P<0.05或P<0.01)。结论:芬戈莫德能减轻RIRI模型小鼠的肾损伤,其机制可能与激活PI3K/Akt信号通路有关。
ABSTRACT: OBJECTIVE: To study the protective effect of fingolimod on renal ischemia reperfusion injury (RIRI) model mice and its mechanism. METHODS: A total of 60 mice were randomly divided into sham operation group, model group, fingolimod group (1 mg/kg) and fingolimod+wortmannin group [fingolimod 1 mg/kg+phosphatidylinositol 3-kinase (PI3K) specific blocker wortmannin 1.4 mg/kg], with 15 mice in each group. Except for sham operation group, RIRI model was induced in other 3 groups, and those model mice were given relevant medicine via caudal vein at once 24 h before surgery. Serum of mice were collected in each group after 24 h perfusion. Serum levels of Scr and BUN were measured by automatic biochemical analyzer. The pathological changes of renal tissue were observed under light microscope. The protein expression of intercellular cell adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1(MCP-1) and phosphorylated protein kinase B (p-Akt) in renal tissue were measured by Western blot assay. RESULTS: Compared with sham operation group, the serum levels of Scr and BUN in model group were increased significantly (P<0.01). Pathological changes were found in the kidney, and RIRI led to widespread renal tubular epithelial cell injury, apoptosis and inflammatory cells infiltration. The protein expression of ICAM-1 and MCP-1 in renal tissue were increased significantly (P<0.01), the protein expression of p-Akt was increased slightly (P>0.05). Compared with mo- del group, other indexes of fingolimod group were improved significantly (P<0.01) except that the protein expression of p-Akt in renal tissue was increased significantly (P<0.01). Compared with fingolimod group, above indexes of fingolimod+wortmannin group were reversed (P<0.05 or P<0.01). CONCLUSIONS: Fingolimod can obviously ameliorate renal injury induced by RIRI in mice, the mechanism of which may be associated with the activation of PI3K/Akt signaling pathway.
期刊: 2018年第29卷第1期
作者: 黄倩,梁青龙,陈慧勤,王梅爱,黄秋虹,郑丹丹,林佩璜
AUTHORS: HUANG Qian,LIANG Qinglong,CHEN Huiqin,WANG Meiai,HUANG Qiuhong,ZHENG Dandan,LIN Peihuang
关键字: 芬戈莫德;肾缺血再灌注损伤;小鼠;磷脂酰肌醇3-激酶;蛋白激酶B
KEYWORDS: Fingolimod; Renal ischemia reperfusion injury; Mice; Phosphatidylinositol 3-kinase; Phosphorylated protein kinase B
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