罗布麻叶提取物对两肾一夹高糖高脂饮食大鼠脂肪性肝病的保护作用

Hepatoprotective effect of Apocynum venetum L extract on fatty liver disease of 2K1C rats with high-fat and refined-carbohydrate diet

目的:探讨罗布麻叶提取物对两肾一夹加高糖高脂饮食大鼠脂肪性肝病的影响.方法:采用两肾一夹术和喂高糖高脂饲料12wk复制代谢综合征大鼠脂肪性肝病模型,第5周测定大鼠收缩压,取收缩压达160mmHg以上的大鼠42只,随机分为罗布麻叶提取物高、中、低剂量组[200、100、50mg/(kg·d),n=8]、卡托普利组[30mg/(kg·d),n=8]和模型组[0.5%羧甲基纤维素5mg/(kg·d),n=10],另设假手术组[0.5%羧甲基纤维素5mg/(kg·d),n=10],按上述设定剂量每天9:00-10:00灌胃一次连续8wk.第13周,称体质量和肝湿质量,测收缩压、血清胰岛素和FFA水平、肝功能、肝组织氧化和抗氧化指标,HE染色观察肝组织形态学改变.结果:模型组大鼠血清胰岛素、FFA、GOT和GPT水平明显升高,肝组织中T-SOD和GSH-Px活力和ISI明显下降,脂质过氧化物MDA含量显著增加,HE染色示肝小叶中大部分肝细胞肿胀,胞质中出现大小不等的脂滴空泡,以大泡性脂肪滴为主,核居边,细胞界限不清,肝窦狭窄,且存在小叶内及门管区炎症细胞浸润.与模型组比较,罗布麻叶提取物高中剂量能明显降低代谢综合征大鼠血清胰岛素、FFA、GOT和GPT水平(41.31±14.46,48.03±10.19vs62.56±19.48;468.52±205.36,584.14±185.89vs830.51±355.17;192.63±67.41,325.18±96.47vs466.16±95.63;49.06±21.52,108.32±38.63vs178.37±66.55,P<0.05或0.01),提高肝组织中T-SOD和GSH-Px活力以及ISI,减少脂质过氧化物MDA含量(83.80±7.10,70.86±11.68vs47.33±12.53;681.85±173.99,481.27±70.05vs250.50±102.97;-5.19±0.44,-5.45±0.31vs-5.79±0.42;17.36±3.45,25.69±5.46vs37.69±4.13,P<0.05或0.01),改善肝细胞的脂质沉积和小叶内及汇管区炎症细胞浸润.结论:罗布麻叶提取物具有抗氧化应激和改善代谢综合征大鼠脂肪性肝病的作用.

AIM： To explore effect of extracts of Apocynum venetum L extract （AVLE） on fatty liver disease of rats with metabolic syndrome. METHODS： Fatty liver disease of rats with metabolic syndrome were copied by two- Kidney, one-Clip method （2KIC） and high-fat and refined-carbohydrate diet for twelve weeks.Systolic blood pressure （SBP） was determined at 5th week. Forty-two rats with SBP exceed- ing 160 mmHg were randomly assigned to five groups： AVLE with high-, middle- and low-dose groups [200, 100, 50 mg/（kg.d）, n = 8], captopril group [30 mg/（kg.d）, n = 8） and model group （0.5% carboxymethylcellulose [5 mg/（kg.d）, n = 10], another laying sham-operation group [0.5% carboxymethylcellulose 5 mg/（kg.d）, n = 10]. Rats were intragastrically administrated between 9：00-10：00 everyday for eight weeks according to above-mentioned setting dosage. At 13th week body weight and liver humid weight were weighed, SBP and functional, oxidative and antioxidative indexes for liver tissue were determined. Pathological changes of liver tissue was observed using hematoxylin-eosin staining method. RESULTS： Levels of insulin, FFA, GOT and GPT in serum were significantly increased in model group; activities of T-SOD and GSH-Px in liver tissue and ISI were notably decreased, and content of lipid perhydride MDA was increased. HE staining revealed that there was hepatic cel- lular swelling in hepatic lobules, inequality of size of lipid droplets （most of fat drops were bullous） in periplast, nucleus on one side, narrowed sinus hepaticus and inflammatory cell infiltration in hepatic lobules and portal area. Decrease levels of insulin, FFA, GOT and GPT for serum （41.31 ± 14.46, 48.03 ± 10.19 vs 62.56 ± 19.48; 468.52 ± 205.36, 584.14 ± 185.89 vs 830.51 ± 355.17; 192.63 ± 67.41, 325.18 ± 96.47 vs 466.16 ± 95.63; 49.06 ± 21.52, 108.32 ± 38.63 vs 178.37 ± 66.55, P 〈 0.05 or 0.01） and content of lipid perhydride MDA （17.36 ± 3.45, 25.69 ± 5.46 vs 37.69 ± 4.13） for liver tissue were obviously observed in high- and middle-dosage AVLE groups; activities of T-SOD and GSH-Px in liver tissue and ISI were notably increased （83.80 ± 7.10, 70.86 ± 11.68 vs 47.33 ± 12.53; 681.85 ± 173.99, 481.27 ± 70.05 vs 250.50 ± 102.97; -5.19 ± 0.44, -5.45 ± 0.31 vs -5.79 ± 0.42, P 〈 0.05 or 0.01）; lipidoses in liver cells and inflammatory cell infiltration in hepatic lobules and portal area were ameliorated. CONCLUSION： AVLE plays a great role in antioxidative stress and has protective effect upon fatty liver disease of rats with metabolic syndrome.