瑞舒伐他汀调控miR-185-3p抑制MAML1和iNOS的表达影响高脂血症引发的大鼠肝损伤的研究

Rosuvastatin regulates the expression of miR-185-3p to inhibit the expression of MAML1 and iNOS affecting liver damage in rats induced by hyperlipidemia

目的探讨瑞舒伐他汀对高脂饮食诱导的高脂血大鼠肝损伤的影响及作用机制。方法将大鼠随机分为对照组、模型组和实验组,每组10只,除对照组外,其余大鼠用高脂饮食复合饮酒喂养构建高脂血症模型,实验组灌胃给予10mg·kg^(-1)瑞舒伐他汀,对照组和模型组灌胃给予10mL·kg^(-1)蒸馏水,连续4周。用酶联免疫吸附(ELISA)测定大鼠血液血脂、肝功能相关指标;用实时定量聚合酶链反应(qRT-PCR)分析微小RNA(miR)-185-3p、策划者样转录共激活因子1(MAML1)的表达情况;用蛋白质印迹法检测MAML1、诱导型一氧化氮合酶(iNOS)的表达情况。结果对照组、模型组和实验组的大鼠肝组织损伤评分分别为(0.32±0.15)、(4.03±1.62)和(2.36±1.14)分;TG分别为(4.95±0.86)、(6.75±1.42)和(5.51±0.91)mmol·L^(-1);TC分别为(2.36±0.48)、(5.11±2.05)和(3.24±1.39)mmol·L^(-1);LDL-C分别为(0.67±0.16)、(1.73±0.42)和(1.03±0.25)mmol·L^(-1);HDL-C分别为(0.72±0.23)、(0.51±0.14)和(0.64±0.11)mmol·L^(-1);GOT分别为(158.31±32.46)、(253.19±49.27)和(187.52±53.46)U·L^(-1);GPT分别为(53.17±6.81)、(79.64±13.92)和(55.63±9.11)U·L^(-1);模型组与对照组相比,大鼠miR-185-3p表达水平显著下调,MAML1、iNOS表达水平均上升;实验组与模型组相比,大鼠肝组织miR-185-3p表达水平显著上调,MAML1、iNOS表达水平均显著下降(均P<0.05)。对照组上述指标与模型组,在统计学上差异均有统计学意义(均P<0.05);模型组的上述指标与实验组比较,在统计学上差异均有统计学意义(均P<0.05)。结论瑞舒伐他汀通过调控miR-185-3p抑制MAML1和iNOS的表达,从而改善高脂血症引发的大鼠肝损伤。

Objective To investigate the effect and mechanism of rosuvastatin on liver injury induced by high fat diet in hyperlipidemia rats.Methods All rats were randomly divided into control group,model group and experimental group,with 10 rats in each group.Except the control group,hyperlipidiosis model rats were fed with high-fat diet combined with alcohol to construct hyperlipidiosis model rats.The experimental group was given 10 mg·kg^(-1)rosuvastatin by gavage,control group and model group were given gavage with 10 mL·kg^(-1)distilled water,once a day for 4 weeks.Serum lipids and liver function were measured by enzyme-linked immunosorbent assay(ELISA).Quantitative real-time polymerase chain reaction(qRT-PCR)was used to analyze the expression of microRNA(miR)-185-3p and mastermind like transcription coactivator 1(MAML1);the expression levels of MAML1 and inducible nitric oxide synthase(iNOS)were detected by Western blot.Results The liver tissue injury scores of control group,model group and experimental group were0.32±0.15,4.03±1.62 and 2.36±1.14;the TG levels were(4.95±0.86),(6.75±1.42)and(5.51±0.91)mmol·L^(-1);the TC were(2.36±0.48),(5.11±2.05)and(3.24±1.39)mmol·L^(-1);the LDL-C were(0.67±0.16),(1.73±0.42)and(1.03±0.25)mmol·L^(-1);the HDL-C were(0.72±0.23),(0.51±0.14)and(0.64±0.11)mmol·L^(-1);the GOT were(158.31±32.46),(253.19±49.27)and(187.52±53.46)U·L^(-1);the GPT values were(53.17±6.81),(79.64±13.92)and(55.63±9.11)U·L^(-1).Compared with the control group,the expression of miR-185-3p in the model group was significantly down-regulated,the expression of MAMLl and iNOS was significantly increased.Compared with the model group,the expression of miR-185-3p in the liver tissue of experimental group was significantly up-regulated,while the expression of MAML1 and iNOS was significantly decreased(all P<0.05).There were statistically significant differences in the above indexes between the control group and the model group(P<0.05);the above data in the model group were statistically significant compared with the experimental group(P<0.05).Conclusion Rosuvastatin inhibits the expression of MAML1 and iNOS by regulating miR-185-3p,thereby improving the liver injury induced by hyperlipidemia in rats.