非诺贝特治疗酒精性与药物性脂肪肝的实验研究

Therapy effects of fenofibrate on alcoholic fatty liver and drug-induced fatty liver in rats

目的 研究非诺贝特对酒精性脂肪肝以及药物性脂肪肝的作用,并探讨两种脂肪肝的发病机制。方法 建立酒精性脂肪肝和药物性脂肪肝大鼠模型并分为治疗组(80 mg/kg)和对照组。4周后处死,分别测定肝功能,血清甘油三酯(TG)、胆固醇(TC)、高密度脂酯(HDL),血清及肝组织丙二醛(MDA)、肝脂酯(HL),脂蛋白脂酶(LPL)及肝脏病理变化。 结果 酒精性脂肪肝非诺贝特组与对照组比较,血清TG治疗组为(1.07±0.06)mmol/L,对照组为(1.56±0.29)mmol/L,血清MDA分别为(1.10±0.22)nmol/L和(1.26±0.21)nmol/L,肝组织内MDA分别为(5.92±1.24)nmol/g和(7.42±1.22)nmol/g,血清内HL分别为(0.053±0.006)μEq·ml-1·h-1和(0.037±0.006)μEq·ml-1·h-1,LPL水平明显升高分别为(0.018±0.004)μEq·ml-1·h-1和(0.014±0.004)μEq·ml-1·h-1;肝组织HL分别为(0.075±0.010)μEq·ml-1·h-1和(0.065±0.007)μEq·ml-1·h-1,LPL分别为(0.022±0.014)μEq·ml-1·h-1和(0.008±0.002)μEq·ml-1·h-1,TC的水平无明显变化,肝内脂质含量分别为(26.01±1.69)mg/g和(71.45±2.66)mg/g,同时肝脏病理明显改善。药物性脂肪肝非诺贝特组与对照组比较肝脏病理改变差异无显著意义。 结论 非诺贝特治疗酒精性脂肪肝可以明显减少肝内脂质的含量。

Objective To investigate the fat decreasing effects of fenofibrate on alcoholic fatty liver and drug-induced fatty liver in rats. Methods Alcoholic fatty liver and drug-induced fatty liver rats models were established. The two kinds of rats with fatty liver were seperatedly divided into fenofibrate treatment group (80mg/kg daily) and control group without treatment.Rats were killed after four weeks, then the levels of serum triglycerides (TG), totalcholesterol (TC), high density lipoprotein (HDL) and malondialdehyde (MDA), hepatic lipase (HL), lipopro-tein lipase (LPL) both in serum and liver tissue were measured according to the Test Kits. Histopathological changes in liver was dyed with HE and observed under light microscope. Results After treatment by fenofibrate, in the serum of rats with alcoholic fatty liver, the level of TG decreased significantly (1.07 mmol/L ± 0.06 mmol/L vs 1.56 mmol/L ± 0.29 mmol/L, t = 5.115, P < 0.001), while the level of TC had no alteration. The levels of MDA both in serum and liver tissue decreased (1.10 nmol/L ?0.22 nmol/L vs 1.26 nmol/L ± 0.21 nmol/L, t = 0.592, P < 0.05; 5.92 nmol/g ± 1.24 nmol/g vs 7.42 nmol/g ±1.22 nmol/g, t = 3.477, P < 0.05, respectively), while the levels of HL, LPL in serum and liver tissue increased significantly (Serum: 0.053 μEq · ml-1· h-1± 0.006μEq· ml-1· h-1 vs 0.037μEq· ml-1· h-1± 0.006μEq · ml-1· h-1, t=-5.086, P < 0.001; 0.018μEq· ml-1·h-1 ± 0.004μEq · ml-1·h-1 vs 0.014μEq· ml-1·h-1± 0.004μEq· ml-1·h-1, t = -2.485, P < 0.05. Liver tissue: 0.075μEq·ml-1·h-1± 0.010μEq· ml-1· h-1 vs 0.065μEq· ml-1· h-1 ± 0.007μEq· ml-1· h-1, t= -2.437, P< 0.05; 0.022μEq· ml-1·h-1± 0.014 μEq · ml-1· h-1 vs 0.008μEq· ml-1·h-1± 0.002μEq·ml-1· h-1, t=-2.876, P< 0.05). Fat content in liver decreased (26.01mg/g ± 1.69 mg/g vs 71.45mg/g ± 2.66mg/g, t = -43.224, P < 0.001). The pathological changes of liver in fenofibrate-treated rats with alcoholic fatty liver were improved. For the drug-induced fatty liver rats, fenofibrate treatment group had no difference from the untreated control group. Conclusions Fenofibrate can significantly decrease the fat content in liver tissue of rats with alcoholic fatty liver, as well as ameliorating liver pathological changes. But fenofibrate has no effect on drug-induced fatty liver.