槲皮素对非酒精性脂肪性肝病大鼠抵抗素和白细胞介素18及胰岛素抵抗影响的研究  

Effects of quercetin on serum levels of resistin and IL-18 and on insulin resistance in nonalcoholic fatty liver disease rats

作　　者：张茂华[1] 梁志清[1] 秦青[1] 李胜联[1] 周冬生[1] 唐灵[1] 

机构地区：[1]广西桂林医学院附属医院感染性疾病科,桂林541001

出　　处：《中华肝脏病杂志》2013年第1期66-70,共5页Chinese Journal of Hepatology

基　　金：广西科技厅自然科学基金（桂科自0991263）;桂林市科学研究与技术开发计划项目（20090539）,广西卫生厅自筹经费科研课题项目（Z2009036）

摘　　要：目的观察槲皮素对非酒精性脂肪性肝病（NAFLD）大鼠血清抵抗素、白细胞介素18（IL-18）和胰岛素抵抗的影响。方法采用高脂饲料对SD大鼠进行造模，造模成功后用不同剂量槲皮素灌胃治疗，疗程为8周。观察肝脏病理变化，并检测治疗前后血清抵抗素、甘油三酯（TG）、IL-18、空腹血糖（FPG）、空腹胰岛素（FINS）和肝组织丙二醛（MDA）的变化，同时计算胰岛素抵抗指数（HOMA—IR）。结果病理结果显示槲皮素灌胃后，高、低剂量组肝细胞的脂肪变性程度均轻于模型组，矿值分别为4．41和2．19，P〈0．05，差异有统计学意义；高剂量组的病变程度较低剂量组轻（U=2．44，P〈0．05）。模型组大鼠血清抵抗素、IL-18、FPG、FINS和HOMA-IR值分别为（1．31±0．22）ng／ml、（18．92±1．29）ng／L、（10．06±3．44）mmol／L、（16．5±5．23）mU／L、2．01±0．98，与高剂量组大鼠的（1．00±0．13）ng／ml、（13．31±1．39）ng／L、（5．34±1．00）mmol／L、（4．66±1．84）mU／L、1．31±0．22比较，t值分别5．98、10．93、7．45、12．69、4．22，尸值均〈0．05，差异均有统计学意义；而低剂量组大鼠的血清抵抗素、IL-18、FPG、FINS和HOMA—IR值量分别为（1．17±0．15）ng／ml、（14．71±2．19）ng／L、（6．90±1．47）mmol／L、（8．49±1．96）mU／L、1．70±0．26与模型组比较，t值分别2．70、8．21、4．99、8．591．87，P值均〈0．05，差异均有统计学意义。高剂量组血清TG和肝组织MDA表达量分别（0．35±0．06）mmol／L、（17．64±5．77）mmol／mgprot，均低于模型组（0．48±0．14）mmol／L和（24．65±4．85）mmol／mgprot，两组比较，t值分别为4．70和5．14，P值均〈0．05，差异有统计学意义。血清抵抗素、TG、IL-18、FPG、FINS和HOMA—IR水平高剂量组均低于低剂量组，f值分别为3．28，3．25，2．72，2．46，4．10，2．3Objeelive To investigate the effects ofquercetin on serum levels ofresistin and interleukin （IL）-I 8 and incidence of insulin resistance （IR） in nonalcoholic fatty liver disease （NAFLD） using a rat model. Methods NAFLD was induced in Sprague-Dawley rats by administering a high-fat diet for four weeks. The model rats were then treated with quercetin （oral gavage administration; low dose group： 75 mg/kg/day, high dose group： 300 mg/kg/day） for eight weeks. Untreated model rats served as controls. Serum levels of resistin, triglyceride fiG）, IL-18, fasting plasma glucose （FPG）, fasting insulin （FINS）, and malondialdehyde （MDA） were measured by standard biochemical assays before and after the quercetin administration. In addition, the insulin resistance index （HOMA-IR） was calculated and pathological changes in liver were observed by histological analysis. Results Compared to the untreated model rats, the quercetin treated model rats showed significantly lower serum resistin （5.98 vs. 2.70）, serum IL-18 （10.93 vs. 8.21）, FPG （7.45 vs. 4.99）, FINS （12.69 vs. 8.59）, and HOMA-IR （4.22 vs. 1.87） （allP 〈 0.01）. Compared to the untreated model group, the high dose group showed significantly lower TG （t = 4.70） and MDA （t = 5.14） （both P 〈 0.01 ）. Serum levels Of resistin and IL-18, and levels ofTG, FPG and FINS were found to be positively correlated with HOMA-IR and the degree of liver disease （r 〉 0, all P 〈 0.05）. The degree of degeneration was dedeased in accordance with the dosages of quercetin, as compared to the untreated model group （U= 4.41 and 2.19, bothP 〈 0.05）, and the pathological degree was less extensive in the high dose group than in the low dose group （U= 2.44, P 〈 0.01）. Conclusion Quercetin treatment reduces levels of inflammatory cytokines and improves lipid peroxidation and IR in NAFLD rats, and its beneficial effects appear to increase with higher dosage.

关 键 词：胰岛素抗药性 槲皮素 抵抗素 白细胞介素18 非酒精性脂肪性肝病 

分 类 号：R575.5[医药卫生—消化系统]