桑白皮药性改变对其降糖功效的影响

Influence of Property Change of Cortex Mori on Its Hypoglycemic Effect

目的:基于以桑白皮配伍对神经系统与内分泌系统活性的影响,探讨桑白皮药性改变对其药性偏向的影响;同时考察与无降糖功效的寒热中药青黛、高良姜合用,增强或降低其寒性,对其降糖功效的影响,以期为中药药性研究提供参考。方法:雄性大鼠,灌胃给予桑白皮0.87 g/kg、桑白皮0.87 g/kg+高良姜0.59 g/kg、桑白皮0.87 g/kg+青黛1.73 g/kg、高良姜0.59 g/kg、青黛1.73 g/kg,连续15 d,观察对正常动物基础指标及神经内分泌系统的影响,初步探讨中药合用对其药性改变的影响。在改变桑白皮药性的基础上,采用雄性昆明种小鼠单次腹腔注射链脲佐菌素(STZ)160 mg/kg, 72 h后检测空腹血糖(FBG),以FBG≥16.7 mmol/L为成模小鼠,灌胃给予桑白皮1.25 g/kg、桑白皮1.25 g/kg+高良姜0.85 g/kg、桑白皮1.25 g/kg+青黛2.49 g/kg、高良姜0.85 g/kg、青黛2.49 g/kg,持续给药四周,检测给药期间体重、日均饮水进食量及给药后空腹血糖(FBG)、血清胰岛素(INS)、C肽、糖化血清蛋白(GSP)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-c)、低密度胆固醇(LDL-c)含量,观察桑白皮药性的改变对其降糖功效的发挥是否有影响。结果:桑白皮合用寒性中药青黛明显降低正常大鼠体重、肛温及5-羟色胺(5-HT)、多巴胺(DA)、去甲肾上腺素(NE)、肾上腺素(EPI)、总三碘甲状腺原氨酸(TT3)、总甲状腺素(TT4)、促甲状腺激素(TSH)、促黄体生成素(LH)水平(P<0.05或P<0.01),明显升高正常大鼠乙酰胆碱酯酶(AChE)水平(P<0.05或P<0.01);而合用热性中药高良姜则显示相反的作用趋势。合用寒性中药青黛能增强其寒性作用趋势,而合用热性中药高良姜能削弱其寒性作用趋势,提示中药合用可以改变药性。同时,对小鼠饮水量、摄食量的影响发现,糖尿病模型与热证模型的表现更为相似。在糖尿病模型实验中,桑白皮能明显降低糖尿病小鼠日均饮水摄食量、FBG含量、血清GSP、TC、TG和LDL-c含量(P<0.05或P<0.01),显著升高C肽和HDL-c含量(P<0.01);合用高良姜后,虽对糖尿病小鼠有一定改善作用,但对糖尿病小鼠饮水摄食量、C肽、GSP、HDL-c和LDL-c的改善作用显著弱于桑白皮;而与无降糖功效的寒性中药青黛配伍使用后,能进一步改善糖尿病小鼠的糖脂代谢紊乱状态,且改善作用明显优于桑白皮单独给药。桑白皮合用典型寒性药青黛能增强其降糖作用,但合用典型热性药高良姜能削弱其降糖作用,提示药性的改变影响药效的发挥。结论:中药合用可以改变药性,且桑白皮寒性影响其降糖功效的发挥。

Objective: Based on the effect of Cortex Mori compatibility on autonomic nervous system and endocrine system, to study the bias of medicinal properties according to property change. At the same time, the influence on its hypoglycemic effect was investigated by the combination of Cortex Mori with Han and Re Chinese medicine(Indigo Naturalis and Alpiniae Officinarum Rhizoma, without hypoglycemic effect) to enhance or reduce its Han property, in order to provide reference for the property study of traditional Chinese medicine. Methods: SD rats were administered with 0.87 g/kg Cortex Mori, 0.87 g/kg Cortex Mori + 0.59 g/kg Alpiniae Officinarum Rhizoma, 0.87 g/kg Cortex Mori+1.73 g/kg Indigo Naturalis, 0.59 g/kg Alpiniae Officinarum Rhizoma and 1.73 g/kg Indigo Naturalis for 15 days, respectively. The effects on the basic indexes of normal animals and neuroendocrine system were observed, to explore the effect of TCM combination on the property change. Based on the property change, male Kunming mice were intraperitoneally injected with 160 mg/kg streptozotocin(STZ) once. FBG was detected after 72 h, mice with FBG≥16.7 mmol/L were selected in the model group, and were orally administered with 1.25 g/kg Cortex Mori, 1.25 g/kg Cortex Mori + 0.85 g/kg Alpiniae Officinarum Rhizoma, 1.25 g/kg Cortex Mori+2.49 g/kg Indigo Naturalis, 0.85 g/kg Alpiniae Officinarum Rhizoma and 2.49 g/kg Indigo Naturalis for 4 weeks. During administration, the body weight, the daily drinking water intake, the contents of fasting glucose(FBG), Insulin(INS), C-peptide, glycosylated serum protein(GSP), TC, TG, HDL-c and LDL-c were detected to observe the influence of medicinal property change of Cortex Mori on its hypoglycemic effect. Results: After combined with Han property Indigo Naturalis, the body weight, the anal temperature, the levels of 5-HT, DA, NE, EPI, TT3, TT4, TSH and LH of normal rats were significantly decreased(P<0.05 or P<0.01), the AChE level was significantly increased(P<0.05 or P<0.01). However, the combination with Re property Chinese medicine Alpiniae Officinarum Rhizoma showed the opposite trend. It was suggested that the combination with Indigo Naturalis enhanced its effect in Han property, while the combination with Alpiniae Officinarum Rhizoma weakened its effect in Han property, which suggested that the combination of traditional Chinese medicine changed its effect in Han property. At the same time, the changes of water consumption and food intake in mice showed that symptoms of the diabetic model were more similar with those of the typical Re syndrome model. In diabetes mice model, Cortex Mori significantly decreased the water consumption, the food intake, the anal temperature, FBG content, and the levels of GSP、TC、TG and LDL-c(P<0.05 or P<0.01), and significantly increased the levels of C peptide and HDL-c(P<0.01). After combined with Indigo Naturalis, although it showed a certain improvement in diabetes mice, the improvement of the water consumption, food intake, anal temperature, C peptide, GSP、HDL-c and LDL-c was weaker than that by Cortex Mori alone. However, after combined with Alpiniae Officinarum Rhizoma, it further improved the disorder of glycolipid metabolism in diabetic mice, and the improvement effect of the drug combination is significantly better than that of Cortex Mori in single use. The combination with Indigo Naturalis enhanced its hypoglycemic effect, but the combination with Alpiniae Officinarum Rhizoma weakened its hypoglycemic effect, indicating that the change of medicinal properties affected the effect of the traditional Chinese medicine. Conclusion: The combination of traditional Chinese medicine can change the medicinal properties, and the Han property of Cortex Mori affects its hypoglycemic effect.