大黄酸改善糖尿病大鼠空腹血糖、胰岛素敏感性并增强肝脏PPARγ和GLUT-2的表达  

Rhein improves fasting blood glucose, insulin sensitivity of diabetic rats and increases expression levels of PPARγ, GLUT-2 in hepatic tissue

作　　者：金苗苗[1] 迟铖[1] 母义明[1] 汪保安[1] 马晓莉[1] 贾贺堂[1] 杨丽娟[1] 窦京涛[1] 陆菊明[1] 潘长玉[1] 

机构地区：[1]解放军总医院内分泌科,北京100853

出　　处：《中华内分泌代谢杂志》2008年第5期537-541,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：973重大基础研究项目（2006CB503903）课题;全军“十一五”中医新药研发项目

摘　　要：目的探讨大黄酸改善高脂喂养联合链脲佐菌素（STZ）诱导糖尿病大鼠血糖及肝脏胰岛素敏感性的作用及其可能机制。方法（1）55只雄性Wistar大鼠随机分为正常对照组（NC，n=15）和糖尿病组（DM，n=40）。NC组以基础饲料喂养，DM组以高脂饲料喂养5周后给予一次性腹腔注射STZ（30mg／kg），其中30只成模大鼠再分为糖尿病模型组（DM-C）和糖尿病大黄酸治疗组（DM-T），后者即开始大黄酸灌胃（100mg·kg^-1·d^-1），灌胃11周后处死动物，收集标本，记录体重、肝重，测定空腹血糖（FBG）、甘油三酯（TG）、总胆固醇（Tc）、HbA。糖化血清蛋白（GSP）等生化指标，放射免疫法测定血清胰岛素浓度（FINS），计算胰岛素敏感指数（ISI）及稳态模型评估的胰岛素抵抗指数（HOMA—IR）。（2）免疫组化法检测肝脏组织中PPARγ的表达，Western印迹法检测肝脏组织中葡萄糖转运蛋白2（GLUT-2）表达。结果实验结束时，测得DM—C组FBG[（22．57±3．23 vs 7．11±1．44）mmol／L，P〈0．01]、TG1（0．89±0．29 vs 0．58±0．17）mmol／L，P〈0．01]、HbAlc[（12．49±1．96 vs 8．36±0．84）％，P〈0．01]、GSP[（57．29±4．14 vs 13．43±2．70）μmol／L，P〈0．01]和肿瘤坏死因子α[TNF-α，（1．365±0．133 vs 1．233±0．159）μg／L，P〈0．05]较NC组均显著升高。DM．C组肝重指数亦明显高于NC组（0．032±0．004vs 0．024±0．002，P〈0．01），FINS与NC组无明显差别，ISI较NC组下降明显[ln（ISI），-5．46±0．61vs-4．81±0．75，P〈0.05]，HOMA-IR较NC组升高[ln（HOMA-IR），2．34±0．64 vs 1．70±0．78，P〈0．05]。DM-C组肝脏PPARγ[11131．7（5723．1-18979．4） vs 48782．1（21576．7-108829．5），P〈0．01]和GLUT-2（0．98±0．35 vs 1．29±0．27，P〈0．05）表达较NC组有明显下降趋势。而DM-T组大鼠的FBG[（15．94±3．16）mmol／L]、HbA1c[（10．51±1．74）％]和GObjective To investigate the effects of rhein on insulin sensitivity of diabetic rats induced by high fat feeding and low dose streptozotocin （ STZ ）, and the possible mechanisms. Methods （ 1 ） Fifty-five Wistar rats were randomly divided into normal control group （NC, n = 15） and diabetes group （DM, n =40）. The NC rats were fed with regular chow and DM rats were fed with high fat diet. Five weeks later, the DM rats were injected with STZ 30 mg/kg once. The 30 diabetic rats were randomly divided into two subgroups, diabetic control group （DM-C） and diabetic group treated with rhein （DM-T）. DM-T rats received intragastric administration of rhein and DM-C rats were given equal doses of solvent. All rats were sacrificed eleven weeks later, the blood sample was collected. The body weight, fasting blood glucose （FBG）, HbA1c, triglycerides （TG）, tolal cholesterol （TC） , glycosylated serum protein （GSP） and Fasting insulin （FINS） concentrations were examined. The insulin sensitive index （ ISI ） and homeostasis model assessment for insulin resistance （ HOMA-IR ） were calculated. （2） The PPARγ and GLUT-2 expression in hepatic tissue were detected by immunohistochemistry and Western-blot. Results At the end of experiment the FBG [ （22.57 ± 3.23 vs 7.11 ± 1.44） mmol/L, P 〈 0.01 ], HbA1c[（12.49±1.96vs8.36±0.84）%,P〈0.01],TG[（0.89±0.29vs 0.58±0.17）mmol/L,P〈0.01] GSP [（57.29±4.14 vs 13.43 ±2. 70）μmol/L, P〈0.01] and tumor necrosis factor-or [TNF-α, （1.365 ± 0. 133 vs 1. 233 ± 0.159 ） μg/L, P 〈 0.05 ] and the liver weight index （0. 032 ± 0. 004 vs 0. 024 ±0. 002, P 〈 0.01 ） in DM-C rats were higher than those in NC rats. Besides, the ISI of DM-C rats decreased [ In（ ISI）, - 5.46 ±0. 61 vs - 4.81 ± 0.75, P 〈 0.05 ] and HOMA-IR elevated [ ln（ HOMA-IR）, 2.34 ± 0.64 vs 1.70 ± 0.78,P 〈 0.05]. The expression of PPAR3, [11 131.7（5 723.1-18 979.4） vs48 782.1（21 576.7-108 829.5）, P〈 0. 01 ] and GLUT-2 （0.

关 键 词：大黄酸 胰岛素敏感性 PPARΓ 葡萄糖转运蛋白2 

分 类 号：R285.5[医药卫生—中药学]