甘草对抗D-半乳糖诱导大鼠糖耐量减低的作用

Effect of glycyrrhiza against impaired glucose tolerance in rats induced by D-galactose

目的:观察甘草拮抗D-半乳糖诱导大鼠糖耐量减低作用,分析该作用性别差异性,并与二甲双胍和水飞蓟宾作对照。方法:实验于2003-03/05在广州市中医中药研究所药理研究室的普通级动物室完成。①选用鼠龄6～8周的SD大鼠103只,雌雄不拘,随机分为5组:正常对照组(n=21)、模型组(n=18)、甘草组(n=22)、二甲双胍组(n=20)、水飞蓟宾组(n=22)。除正常对照组腹腔注射等量溶媒代替D-半乳糖连续56d外,其余组大鼠腹腔注射D-半乳糖150mg/kg,1次/d,连续56d造成糖耐量减低模型。在后42d造模同时,甘草组:按0.44g/(kg·d)剂量灌胃甘草混悬液(主要成分:甘草,由广东一方制药厂生产,批号:020315,5g/袋,将甘草颗粒剂用蒸馏水配成混悬液);二甲双胍组:以0.25g/kg剂量灌胃二甲双胍(由深圳中联制药厂生产,生产批号:200212305,0.5g/片)溶液;水飞蓟宾组:以0.25g/kg剂量灌胃水飞蓟宾(由江苏中兴药业有限公司生产,批号:20030303,50mg/片)溶液;均1次/d,连续42d。②造模成功后,大鼠称体质量,测空腹血糖和口服葡萄糖耐量试验后2h血糖,计算空腹血糖与餐后2h血糖差值。③计量资料差异比较采用t检验(方差不齐,用t’检验)。结果:大鼠103只均进入结果分析。①模型组大鼠空腹血糖与正常对照组接近,但口服葡萄糖耐量试验后2h血糖明显高于正常对照组(t=6.5214,P<0.01),即糖耐量减低的胰岛素抵抗状态;而甘草组、二甲双胍组、水飞蓟宾组大鼠体质量和空腹血糖与模型组相近(P>0.05),口服葡萄糖耐量试验后2h血糖明显低于模型组(t=3.585～5.980,P<0.01),空腹血糖与口服葡萄糖耐量试验后2h血糖差值明显低于模型组(t=2.897～6.094,P<0.01),即改善D-半乳糖诱导胰岛素抵抗大鼠的糖耐量减低。另外,模型组大鼠体质量低于正常对照组,但差异不明显(P>0.05)。雄性大鼠各指标组间差异同前。②模型组雌鼠空腹血糖和口服葡萄糖耐量试验后2h血糖明显高于正常对照组(t=3.4014,6.858,P<0.01),即糖耐量减低的胰岛素抵抗状态。甘草组、二甲双胍组雌鼠空腹血糖明显低于模型组(t=2.288,2.301,P<0.05),水飞蓟宾组雌鼠空腹血糖与模型组相近(P>0.05);3个给药组雌鼠口服葡萄糖耐量试验后2h血糖和空腹血糖与口服葡萄糖耐量试验后2h血糖间血糖差值明显低于模型组(t=4.1763～6.3716,P<0.01),即能改善糖耐量减退。另外,各给药组雄鼠体质量与正常对照组和模型组相近(P>0.05)。结论:①D-半乳糖可诱导以糖耐量减低为表现的胰岛素抵抗,以雌性大鼠更为明显。②甘草、二甲双胍和水飞蓟宾均能改善D-半乳糖诱导胰岛素抵抗大鼠的糖耐量。

AIM; To investigate the effects of glycyrrhiza on impaired glucose tolerance （IGT） induced by D-galactose （D-gal） in rats, analyze the sex differences and compare with metformin and silibinin. METHODS： The experiment was conducted at the Common Animal Laboratory, Department of Pharmacology, Guangzhou Institute of Traditional Chinese Medicine and Materia Medica.①Totally 103 SD rats of 6-8 weeks old and either sex were .randomly divided into 5 groups： control group （n=21）, model group （n=18）, glycyrrhizia group （n=22）, metformin group （n=20） and silibinin group （n=22）. The solvent of same dose was injected intraperitoneally continuously for 56 hours in the control group while 150 mg/kg D-gol was given intraperitoneally in other groups, once a day continuously for 56 days to establish the IGT models. From the 14^th day of model establishment, 0.44 g/kg glycyrrhizia suspension （main component： glycyrrhizia, produced by Guangdong Yifang Pharmaceutical Company, batch number：020315, 5 g/pocket, suspension was obtained by the distilled water mixing glycyrrhizia granules） was administrated intragastricallly in the glycyrrhizia group, while 0.25 g/kg silibinin solution （produced by Jiangsu Zhongxing Pharmacy Company Limited, number： 20030303, 50 rag/sheet） and 0.25 g/kg metformin solution （produced by Shenzhen Zhonglian Pharmaceutical Company, batch number： 200212305, 0.5 g/sheet） were given intragastrically in the silibinin group and the metformin group, respectively. The three kinds of solutions were given once a day continuously for 42 days.②After the model establishment, the body mass of rats was weighed. The fasting blood glucose （FBG） and 2-hours blood glucose （2hBG） after oral glucose tolerance test （OGTF） detected and the different value was compared. ③The measurement data were compared with t test （The t＇test was used for variance nonhomogeneity）. RESULTS：Totally 103 rats were involved in the result analysis.①FBG in the groups of control, glycyrrhiza, metformin and silibinin were similar with that in the model group （P 〉 0.05）, while the content of 2hBG after OGTI＂ was significantly higher in model group than in groups of control, glycyrrhiza, metformin and silibinin （t=6.521 4, t=3.586-5.980,P 〈 0.0l）,which showed the insulin resistance for IGT. The difference between FBG and 2hBG after OGTI＇ was lower in the groups of glycyrrhiza, metformin and silibinin than in the model group （t=2.897-6.094,P 〈 0.01）,which indicated the improvement in D-gal-induced 1GT. Moreover, ,the body mass of rats in model group was similar with that in groups of glycyrrhiza, metformin and silibinin, and lower than that of control group, with the insignificant difference （P 〉 0.05）. So did the difference between groups in male rats. ②FBG and 2hBG after OGTY of female rats .in the model group were significantly higher than that in the control group （t=3.401, 6.858,P 〈 0.01）, which showed the insulin resistance for IGT. The FBG of female rats in glycyrrhiza and metformin groups were significantly lower than that in the model group （t=2.288,2.301,P 〈 0.05） while the FBG in silibinin group was not different from that in model groap （P 〉 0.05）; 2hBG after OGTY of female rats of three medication groups were significantly lower than that in the model group, and the differenee between FBG and 2hBG after OGTF of female rats in three medication groups were significantly lower than that in the model group （t=4.176 3-6.371 6,P 〈 0.01）, which indicated the improvement of IGT, The body mass of male rats in the medication groups was not different from thuse in control group and model group （P 〉 0.05）. CONCLUSION： ①D-gal can induce the insulin resistance expressed as IGT,. particularly in the female rats. ②The glycyrrhizin, mettbrmin and silibinin can antagonize D-gal-induced insulin resistance and improve IGT,