机构地区:[1]广州中医药大学中药学院,广东广州510006
出 处:《中药新药与临床药理》2018年第1期1-7,共7页Traditional Chinese Drug Research and Clinical Pharmacology
基 金:国家自然科学基金项目(81503375;81373775);广东省自然科学基金项目(2015A030313350);广州中医药大学青年英才培养工程项目(QNYC20170107)
摘 要:目的观察黄芪散有效部位群(HQS)对Ⅱ型糖尿病大鼠肝糖原含量及糖异生酶的影响。方法采用低剂量链脲佐菌素(STZ)腹腔注射联合高脂饲料喂养建立Ⅱ型糖尿病大鼠模型,造模同时给予HQS(2.4 g·kg-1)灌胃给药,连续16周。给药12周进行口服葡萄糖耐量实验(OGTT),测定不同时间点血糖浓度,计算血糖-时间曲线下面积(AUC);给药14周测定空腹血糖(FBG)、空腹胰岛素(FINS),计算胰岛素抵抗指数(HOMA-IR);测定大鼠体质量、肝脏质量,计算肝脏系数;采用HE染色观察肝脏组织和细胞结构;采用过碘酸-希夫(PAS)染色观察肝细胞糖原颗粒并测定肝糖原含量;q PCR法检测磷酸烯醇式丙酮酸羧激酶(PEPCK)、葡萄糖-6-磷酸酶(G6Pase)m RNA表达。结果与正常组比较,模型组大鼠的FBG、FINS、HOMA-IR、OGTT不同时间点血糖值、AUC值、大鼠体质量、肝脏质量以及肝脏系数均显著升高,肝脏中PEPCK及G6Pase m RNA表达水平亦明显升高,差异有统计学意义(P<0.05,P<0.01,P<0.001)。与模型组比较,HQS组的FBG、FINS、HOMA-IR水平、OGTT第0,60,120 min血糖值及AUC值、大鼠的体质量、肝脏质量及肝脏系数均显著降低,肝脏PEPCK m RNA表达亦明显下降,差异有统计学意义(P<0.05,P<0.01,P<0.001),G6Pase m RNA表达有明显下降的趋势,但差异无统计学意义(P>0.05)。结论 HQS通过增加肝糖原合成及下调糖异生酶的表达来抑制糖异生,从而改善Ⅱ型糖尿病大鼠肝脏胰岛素抵抗。Objective To observe the effects of Huangqi san effective fractions(HQS)on hepatic glycogen content and gluconeogenesis enzymes in type 2 diabetes mellitus(T2DM)rats.Methods The T2DM model rats were produced by intraperitoneal injection of low-dose streptozotocin(STZ) and feeding with high-fat diet.At the same time,rats were administered intragastrically with HQS(2.4 g·kg^-1)once a day for 16 weeks.After intervention by drugs for 12 weeks,oral glucose tolerance test(OGTT) was carried out.The blood glucose contents of different time points were measured,and the blood glucose-time area under curve(AUC) was calculated.After intervention by drugs for 14 weeks,fasting blood glucose(FBG),fasting insulin levels(FINS),insulin resistance index(HOMA-IR),liver weight and liver coefficient of all rats were measured.The liver pathological changes and liver glycogen granule were observed by HE staining and PAS staining,respectively;and the content of glycogen was also measured.The gene expression of phosphoenolpyruvate carboxykinase(PEPCK m RNA) and glucose-6-phosphatase(G6 Pase m RNA) of all rats were measured by quantitative PCR(q PCR).Results As compared with control group,the FBG,EINS,HOMA-IR,glucose contents of different time points in OGTT,AUC,body weight,liver weight and liver coefficient,and the gene expression of PEPCK and G6 Pase in model group rats were all increased with statistically significant levels(P <0.05,P < 0.01,P < 0.001).As compared with model group,HQS significantly reduced the FBG,FINS,HOMA-IR,the blood glucose of 0,60,120 min in OGTT and AUC;decreased body weight,liver weight and liver coefficient of rats,and also notably reduced the expression of liver PEPCK m RNA with statistically significant levels(P < 0.05,P< 0.01,P < 0.001).The expression of G6 Pase m RNA showed a downward trend although it was not significantly influenced by HQS.Conclusion HQS improved the hepatic insulin resistance by increasing liver glycogen synthesis,downregulating the expression of gluconeogenesis enzyme and inhibiting glu
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