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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。
OBJECTIVE: To observe the expression of P38 mitogen activated protein kinase (P38MAPK) in nonalcoholic fatty liver disease (NAFLD) and its effect on inflammatory reaction in rats and to explore the role of P38MAPK signal transduction Pathway in NAFLD role. Methods: Thirty-six adult male Sprague Dawley rats were randomly divided into control group, high glucose model group and SB203580 intervention group, with 12 rats in each group. The rats in high glucose group were given non-alcoholic steatohepatitis (NASH) model by high-carbohydrate diet for 12 weeks. SB203580 intervention group were intraperitoneal injected with SB203580 once a week for 12 weeks After sacrifice, specimens were taken. The histopathology of each group was observed. The levels of serum biochemistry, liver index, insulin resistance and the content of inflammatory cytokines in liver homogenates were determined. The expression of p38MAPK and p-p38MAPK in liver were detected by Western blot. Results: Compared with the control group, the hepatic steatosis in the high glucose group showed obvious hepatic steatosis. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) Glu, Cholesterol (CHO) and triglyceride (TG) were significantly increased, and liver index, insulin resistance and tumor necrosis factor-α (TNF- α and Interleukin (IL) -6 were significantly increased in the SB203580 intervention group than in the high glucose model group. Compared with the control group, the expression of P-P38MAPK in liver tissue of high glucose group was significantly increased. Compared with high glucose group, the expression of PP38MAPK in SB203580 group was significantly decreased. The expression of P38MAPK in each group was not statistically significant. CONCLUSION: P38MAPK signal transduction pathway is involved in the regulation of inflammatory cytokines in NAFLD of rats and plays an important role in NASH. Inhibition of P38MAPK may be a potential effective means of intervention for NAFLD.