目的:观察小檗碱及其衍生物对2型糖尿病大鼠骨骼肌蛋白酪氨酸磷酸酯酶1B(PTP1B)蛋白表达的影响。方法:采用尾静脉注射小剂量链脲佐菌素(STZ)和高脂高热卡饮食喂养的方法建立大鼠2型糖尿病模型。随机分为模型组、小檗碱组、8-羟基二氢小檗碱(Hdber)高、中、低剂量组和二甲双胍组,另设正常对照组。干预8周后,检测各组大鼠血糖、血脂、空腹胰岛素(FINS)水平及骨骼肌PTP1B、胰岛素受体β(InsRβ)亚基蛋白及其酪氨酸磷酸化水平的差异。结果:与正常组比较,模型组大鼠血糖升高,血脂代谢紊乱,FINS及骨骼肌PTP1B蛋白表达升高(P〈0.05,P〈0.01),而InsRβ亚基蛋白表达及其酪氨酸磷酸化水平降低(P〈0.01);与模型组比较,各治疗组代谢紊乱均得到明显改善、FINS降低(P〈0.05,P〈0.01),但骨骼肌组织PTP1B蛋白表达水平无明显差异;与小檗碱组比较,Hdber中高剂量组对各指标的改善程度相接近。结论:小檗碱及Hdber均可改善2型糖尿病大鼠糖脂代谢紊乱,其机制可能与增加骨骼肌组织InsRβ亚基蛋白表达及其酪氨酸磷酸化水平有关,而未观察到其对PTP1B蛋白表达水平的显著影响。
OBJECTIVE To explore the effects of berberine and its derivatives on the expression of PTP1B protein in skeletal tissues of type 2 diabetic rats.METHODS The rat model of type 2 diabetes was established by intravenous injection of small doses of streptozotocin and feeding a high-fat diet for 8 weeks.The rats were randomly divided into diabetic group,berberine group,8-hydroxy dihydroberberine(Hdber) groups with different doses,and metformin group.Meanwhile,another normal group of rats was established as control.After eight weeks treatment,blood glucose,plasma lipid profiles,fasting plasma insulin(FINS) levels,the expressions of PTP1B,insulin receptorβ(InsRβ) protein and phospho-tyrosine level of InsRβ in skeletal tissues were detected.RESULTS Compared with the control group,the plasma glucose,serum lipids and FINS in diabetic group were elevated.Skeletal expression of PTP1B protein was increased,while InsRβ protein and its phospho-tyrosine level were decreased significantly(P〈0.05,P〈0.01).Compared with model group,the addition of berberine or Hdber reversed the above abnormalities(P〈0.05,P〈0.01) except skeletal expression of PTP1B protein was not significantly changed.The difference of the hypoglycemic and lipid-regulating effects between berberine group and high and middle doses Hdber groups were hardly observed.CONCLUSION Berberine and its derivative are effective on regulating glucose and lipid metabolism disturbance in type 2 diabetic rats.The therapeutic mechanism is possibly related to the increase of the expression of InsRβ protein and its phospho-tyrosine level,and the influence of berberine and its derivative on the expression of PTP1B protein in skeletal tissue was not demonstrated.