胰升血糖素样肽1对非酒精性脂肪性肝病大鼠氧化应激损伤的干预

Influence of GLP-1 on oxidative stress injury in non-alcoholic fatty liver disease rats

目的通过建立大鼠非酒精性脂肪性肝病（NAFLD）模型，观察胰升血糖素样肽1（GLP-1）对NAFLD大鼠氧化应激损伤的干预效应。方法60只雄性SD大鼠分为正常饮食组（NC组，n=15）和高脂饮食组（HF组，n=45），12周末评估NAFLD模型的建立。NC组给予等渗盐水干预，HF组再分为等渗盐水组（NS组，n=10），低剂量GLP-1组（LG组，n=10），中剂量GLP-1组（MG组，n=10），高剂量GLP-1组（HG组，n=10），给予等渗盐水及不同剂量（50μg／kg，100μg／Kg，200μg／kg）GLP-1进行干预，4周后检测血清生物化学指标（甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白、ALT、AST），肝组织超氧化物歧化酶、丙二醛及细胞色素氧化酶P450 2El（CYP2E1）mRNA和蛋白含量。两个样本均数比较采用t检验或近似t检验，多个样本均数比较采用LSD检验或Dunnett T3检验。结果NS组超氧化物歧化酶水平较NC组显著降低[（165.81±11.64）U／mg对比（192.89±16.53）U／mg，P〈0.05]，丙二醛水平显著升高[（7.30±1.79）nmol／mg对比（3.10±1.30）nmol／mg，P〈0.05]，CYP2E1 mRNA及蛋白含量亦明显升高（P〈0.05）。经过GLP-1干预后，与NS组比较，LG、MG、HG组大鼠肝组织超氧化物歧化酶水平呈升高趋势[（171.44±9.80）U／mg对比（177.66±14.77）对比（186.17±15.43）U／mg，仅HG组，P〈0.05]，MDA水平明显降低[（5.16±1.45）nmol／mg对比（4．08±1．22）nmol／mg对比（3.31±1.14）nmol／mg，P〈0.05]，CYP2E1 mRNA和蛋白水平亦呈降低趋势（CYP2E1 mRNA含量仅HG组差异有统计学意义，P〈0.05}CYP2E1蛋白含量在MG、HG组差异均有统计学意义，P值均〈0.05）。结论GLP-1可改善肝组织脂质沉积，减轻NAFLD大鼠氧化应激损伤。

Objective To investigate the effects of ghcagon-like peptide-1 （GLP-1） on liver oxidative stress injury using a rat model of non-alcoholic fatty liver disease. Methods Sixty male Sprague-Dawley rats were fed 12 weeks of either a diet of normal chow （NC）, for use as controls（n= 15） or high-fat chow （HF）, for use as models （n = 45）. The NC rats were administered normal saline, while the HF rats were treated with either normal saline （N S）, for use as untreated model controls （n = 10）, low-dose GLP-1 （LG, 50 μg/kg; n = 10）, mid-dose GLP-1 （MG, 100μg/kg; n = 10）, or high-dose GLP-1 （HG, 200 lag/kg;n = 10）; all treamaants lasted for 4 weeks. The rats＇ weight, levels of serum biochemical markers （triglycerides, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, alanine aminotransferase, and aspartate aminotransferase）, levels of superoxide dismutase （SOD） and malondialdehyde （MDA）, and expression of CYP2E1 mRNA and protein in liver homogenates were measured. TheFtest, t-test, least significant difference test and Dunnett＇s T3 test were usedfor statistical analyses. Results Compared with the NC group, the rats in the NS group showed significantly lower SOD （165.81±11.64 vs. 192.89±16.53 U/mg, P〈 0.05）, significantly higher MDA （7.30±1.79 vs. 3.10-±1.30 nmol/ mg, P 〈 0.05）, and significantly higher expressions of CYP2E1 rnRNA and protein （both P 〈 0.05）. After GLP- 1 treatment, the rats in the LG, MG and HG groups showed increased levels of SOD （compared to the NS group; 171.44±9.80 vs. 177.66±14.77 vs. 186.17±15.43 U/mg; only the HG group hadP 〈 0.05）, significantly decreased levels of MDA （compared to the NS group; 5.16±1.45 vs. 4.08±1.22 vs. 3.31±1.14 nmol/mg; all P 〈 0.05], and decreased levels of CYP2E1 mRNA and protein expressions （CYP2E1 mRNA： only the HG group hadP 〈 0.05; CYP2E1 protein： both the MG and HG groups hadP 〈 0.05）. Conclusion GLP-1 treatment can improve oxidative stress injury, suggesting its potential as a therapeutic agent for non-alcoholic fatty liver disease.