P38丝裂原活化蛋白激酶在大鼠非酒精性脂肪肝中的作用

发布时间：2018-07-17 08:35

【摘要】：目的:观察P38丝裂原活化蛋白激酶(p38 mitogen activated protein kinase,P38MAPK)在大鼠非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)中的表达以及对炎症反应的影响,探讨P38MAPK信号转导通路在NAFLD中的作用。方法:清洁级成年雄性SD大鼠36只,随机分为对照组、高糖模型组和SB203580干预组,每组12只。高糖模型组大鼠经高糖饮食12周造成非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)模型;SB203580干预组大鼠在给予高糖饮食的同时并每周腹腔注射1次SB203580;12周后处死,留取标本。观察各组肝组织病理学形态,测定血清生化、肝指数、胰岛素抵抗和肝匀浆中炎症因子的含量,免疫印迹法测定肝中p38MAPK、p-p38MAPK的表达。结果:与对照组比较,高糖模型组肝组织病理学显示肝脂肪变性明显,血清中丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspertate aminotransferase,AST)、葡萄糖(glucose,Glu)、胆固醇(cholesterol,CHO)、甘油酯(triglyceride,TG)明显升高,肝指数、胰岛素抵抗评估和肝匀浆中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白介素(Interleukin,IL)-6均明显升高;SB203580干预组上述指标较高糖模型组明显减轻。与对照组比较,高糖模型组大鼠肝组织P-P38MAPK表达明显增加;与高糖模型组比较,SB203580干预组PP38MAPK表达明显降低。各组大鼠P38MAPK表达无统计学意义。结论:P38MAPK信号转导通路参与了大鼠NAFLD中炎症因子的调控,在NASH中起着重要作用,对P38MAPK的抑制可成为干预NAFLD的潜在有效手段。
[Abstract]:Aim: to investigate the expression of p38 mitogen activated protein kinase- p38 MAPK and its effect on inflammatory response in rats with non-alcoholic fatty liver disease (NAFLD), and to investigate the role of P38 MAPK signal transduction pathway in NAFLD. Methods: Thirty-six adult male SD rats of clean grade were randomly divided into control group, high glucose model group and SB203580 intervention group with 12 rats in each group. The rats in the high glucose model group were killed after 12 weeks of high glucose diet and SB203580 rats were given high glucose diet and intraperitoneally injected SB203580,12 weeks later, the model of nonalcoholic steatohepatitis Nash was established. The rats in the intervention group were sacrificed after 12 weeks of hyperglycemic diet and intraperitoneal injection of SB2035800.The rats in SB203580 intervention group were sacrificed after 12 weeks of high glucose diet. The liver histopathology, serum biochemistry, liver index, insulin resistance and the content of inflammatory factors in liver homogenate were observed. The expression of p38 MAPK- p-p38 MAPK in liver was detected by Western blot. Results: compared with the control group, the liver histopathology of the high glucose model group showed obvious steatosis, and the serum levels of alanine aminotransferase (alt), aspertate aminotransferase (AST), glucose glutamate (Glu), cholesterol (cholesterol), triglyceride (TG) were significantly increased, and the liver index was increased. The evaluation of insulin resistance and the increase of TNF-伪 (tumor necrosis factor- 伪 TNF- 伪 and interleukin (IL)-6 in liver homogenate were significantly reduced in SB203580 intervention group than in high glucose model group. Compared with the control group, the expression of P-P38 MAPK was significantly increased in the high glucose model group, and the expression of PP38 MAPK in the SB203580 intervention group was significantly lower than that in the high glucose model group. There was no significant difference in the expression of P38 MAPK in all groups. Conclusion the proportion of P38 MAPK signal transduction pathway is involved in the regulation of inflammatory factors in NAFLD and plays an important role in Nash. The inhibition of P38 MAPK may be a potential effective means to interfere with NAFLD.
【作者单位】：贵州航天医院消化内科;重庆医科大学附属第二医院消化内科;
【基金】：贵州省科技厅资助项目(编号:黔科合J字[2011]2258号)
【分类号】：R575.5

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