豹皮樟总黄酮降低2型糖尿病大鼠血糖的可能机制研究

目的探讨豹皮樟总黄酮降低2型糖尿病(T2DM)大鼠血糖的可能机制。方法 T2DM大鼠给予豹皮樟总黄酮(total flavonoids of litsea coreana,TFLC,400mg/kg)或阳性对照药二甲双胍(MET,400mg/kg)灌胃治疗6周。各组大鼠空腹血清作常规生化指标测定,肝脏作HE染色和透射电镜观察;肝匀浆作丙二醛(MDA)和超氧化物歧化酶(SOD)分析;RT-PCR检测大鼠肝脏中蛋白酪氨酸磷酸酶1B(protein tyrosine phosphatase 1B,PTP1B)的表达。结果糖尿病大鼠经TFLC或MET治疗后葡萄糖耐量明显改善,空腹血糖(FBG)、糖化血红蛋白(HbA1c)、胰岛素(FINS)、游离脂肪酸(FFA)、总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)显著下降,高密度脂蛋白胆固醇(HDL-C)明显增加,肝匀浆MDA含量下降,SOD活性升高,2个治疗组的各指标之间差异无统计学意义。光镜下T2DM组肝脏有明显的脂肪变性,电镜下肝脏线粒体肿胀,内质网断裂,TFLC组和MET组均有不同程度的改善。T2DM组肝脏中PTP1B的表达明显升高,TFLC组PTP1B表达显著降低,MET组PTP1B的表达无明显改变。结论 TFLC可明显降低血糖和血脂,减轻肝脏组织的氧化应激,其改善胰岛素抵抗,可能与其降低T2DM大鼠肝脏中PTP1B的表达,增强胰岛素信号通路有关。

Study on the Mechanism of Action of Total Flavonoids of Litsea Coreana for Reducing Blood Glucose Level in Rat with Type 2 Diabetes Mellitus

Objective To explore the possible mechanism of total flavonoids of Litsea coreana （TFLC） on reducing blood glucose level in rat with type 2 diabetes mellitus （T2DM）. Methods Male SD rats of T2DM allocated in two groups were treated with 400 mg/kg TFLC or metformin respectively via gastrogavage for 6 weeks. Blood routine biochemical indices in rats were measured; pathology of rats＇ liver was examined with HE stain under transmission electron microscopy; levels of malondialdehyde （MDA） and superoxide dismutase （SOD） in liver homogenate were determined,and the expression of protein tyrosine phosphatase1B （PTP1B） in liver was detected using RT-PCR at the terminal of the experiment. Results Biochemical measuring showed that the glucose tolerance of rats after treatment was markedly improved in both groups. Meantime,levels of fast blood glucose （FBG）,glycohemoglobin （HbA1c）,fast blood insulin （FINS）,free fatty acid （FFA）,total cholesterol （TC）,triglyceride （TG） and low density lipoprotein-cholesterol （LDL-C）,as well as MDA level in liver were decreased,while levels of high density lipoprotein-cholesterol （HDL-C） in blood and SOD in liver were significantly increased in both groups after treatment,showing insignificant difference between two treatment groups. Light microscopic examination showed markedly fatty degeneration of liver,and electron microscopic examination found mitochondria swelling and endoplasmic reticulum breakage in liver of T2DM rats,but these changes were ameliorated to some extent after treatment. The elevated PTP1B expression in liver of T2DM rats was decreased in the TFLC treated group,but unchanged in the metformin treated group. Conclusion TFLC can significantly decrease the blood levels of glucose and lipid and ameliorate oxidation stress in liver; its mechanism of action in improving insulin resistance might be related with its suppression on PTP1B expression in rat＇s liver to enhance the insulin signaling pathway.