非诺贝特对高脂血症大鼠肝脏氧化应激和内质网应激的影响

摘要

目的：研究非诺贝特对高脂血症大鼠肝脏氧化应激和内质网应激的影响。方法：12周高脂饮食建立高脂血症大鼠模型，非诺贝特[100 mg /（kg·d）]灌胃治疗4周。糖耐量和胰岛素耐量实验分析胰岛素抵抗的改善作用，检测大鼠空腹血糖、胰岛素、血脂指标，油红染色分析肝脏脂质沉积，肝匀浆测定总 SOD、GSH和 T-AOC 等氧化应激指标，Realtime RT-PCR、Western blot 分析肝组织 GRP78的 mRNA 和蛋白表达变化。结果：高脂血症大鼠经非诺贝特治疗后糖耐量和胰岛素耐量明显改善，空腹血胰岛素、TG、TC 水平均显著降低（P ＜0．05），肝脏组织切片中脂滴的数目和大小均明显减少，T-SOD 水平明显升高（P ＜0．05），GSH 和 T-AOC水平升高，但差异无显著性（P ＞0．05），GRP78的 mRNA、蛋白表达显著升高（P ＜0．05）。结论：非诺贝特具有明显的改善胰岛素抵抗和调脂作用，可能与其减少氧化应激进而降低内质网应激有关。%Objective To study the influences of fenofibrate on oxidative stress and endoplasmic reticulum stress in livers of hyperlipidemic rats. Methods Male SD rats were fed with high-fat diet for 12 weeks to induce a model of hyperlipidemia, then divided into control group, high-fat diet group with another four-week high-fat diet and fenofibrate group, in which rats were treated with fenofibrate [100 mg / (kg·d)] for 4 weeks. Then improvement of insulin resistance was detected in rats with GTT and ITT experiment. The serum levels of glucose (GLU), fasting insulin (FINS),triglyceride (TG) and total cholesterol (TC) were detected. The pathological changes of livers were detected with Oil Red O staining. The oxidative stress indices such as T-SOD, Mn-SOD, GSH and T-AOC were detected with liver homogenate. The expression of GRP78 was detected with real-time quantification RT-PCR and Western blot analysis respectively. Results Compared with rats with high-fat-diet, rats after fenofibrate treatment showed obviously improved insulin resistance, lower serum level of TG, TC and FINS (P < 0.05), decreased number and size of lipid droplets in liver tissue sections. T-SOD level in liver homogenate was significantly increased (P < 0.05), while GSH and T-AOC levels increased but had no obvious differences when compared with control group (P > 0.05). The expression of GRP78 at mRNA and protein levels were increased significantly after fenofibrate treatment (P < 0.05). Conclusions Fenofibrate has significant effects on improving insulin resistance and lipid regulation, which might be related to decreased oxidative stress and subsequent endoplasmic reticulum stress.