绞股蓝与黄芩防治糖尿病心脏病的协同作用研究

Study on the Synergistic Effect between Gynostemma pentaphyllum and Scutellaria baicalensis in Control of Diabetic Cardiopathy

摘要:

目的: 探讨绞股蓝与黄芩在防治糖尿病心脏病方面可能存在的协同作用及相关机制。 方法: 体外考察绞股蓝提取物(GP),黄芩提取物(SBG),以及绞股蓝提取物与黄芩提取物的混合物(GPSBG)各0.5,5,50 mg·L^-1对血管内皮细胞、心肌细胞以及系膜细胞的直接作用;采用高脂大鼠加静脉注射链脲佐菌素(STZ)25 mg·kg^-1诱导糖尿病心脏病大鼠模型,将造型成功的动物随机分为GP 300 mg·kg^-1,SBG 300 mg·kg^-1,GPSBG 600 mg·kg^-1以及模型组,每天灌胃给药1次,连续8周,末次给药后24 h测定各心脏血流动力学相关指标,并取血测定血脂。 结果: SBG 5 mg·L^-1可对抗高糖抑制血管内皮细胞ECV-304生长(P<0.05)、增加一氧化氮(NO)生成(P<0.05),抑制系膜细胞增殖(P<0.001);GPSBG 5 mg·L^-1可对抗高糖抑制ECV-304生长(P<0.05)、增加一氧化氮(NO)生成(P<0.001)、降低谷胱甘肽(GSH)水平(P<0.001)的作用,抑制系膜细胞增殖(P<0.001);GP 5 mg·L^-1可对抗H₂O₂抑制心肌细胞生长(P<0.05)、增加NO生成(P<0.05)、降低GSH水平(P<0.05)的作用;SBG 0.5 mg·L^-1可以减少H₂O₂环境下心肌细胞的NO生成(P<0.05),提高GSH(P<0.05)水平;GPSBG 5 mg·L^-1均可对抗H₂O₂抑制心肌细胞生长(P<0.05)、增加NO生成(P<0.05)、降低GSH水平(P<0.001)的作用;GP 300 mg·kg^-1,SBG 300 mg·kg^-1可抑制Ⅱ型糖尿病大鼠心脏指数的增加(P<0.05),GPSBG 600 mg·kg^-1则可显著降低Ⅱ型糖尿病大鼠血清甘油三酯(TG)、总胆固醇(TC)水平以及心脏指数(P<0.05或P<0.001),GP 300 mg·kg^-1可显著增加Ⅱ型糖尿病大鼠心率、左室收缩压、左室舒张末期压、左室收缩及舒张时间变化率等指标,降低左室舒张末期压(P<0.05);SBG 300 mg·kg^-1可显著降低Ⅱ型糖尿病大鼠左室舒张末期压(P<0.05);GPSBG 600 mg·kg^-1可显著增加Ⅱ型糖尿病大鼠心率、左室收缩压、左室收缩及舒张时间变化率,降低左室舒张末期压(P<0.01或P<0.001)。 结论: 上述研究结果显示:GP,SBG在改善Ⅱ型糖尿病大鼠心脏功能方面表现出明显的协同增效作用,这可能与黄芩、绞股蓝均有降低Ⅱ型糖尿病大鼠血清TG,TC水平的趋势,并能在内皮细胞、心肌细胞、系膜细胞以及醛糖还原酶等方面作用有关。

Abstract:

Objective:To study the synergistic effect between Gynostemma pentaphyllum (GP) and Scutellaria baicalensis Georgi (SBG) in control of diabetic cardiopathy(DC), providing the scientific basis for the clinical application. Method: The in vitro effects of GP (0.5, 5, 50 mg·L^-1), SBG (0.5, 5, 50 mg·L^-1) and the mixture of GP extract and SBG extract (GPSBG, 0.5, 5, 50 mg·L^-1) on vascular endothelial cells, myocardial cells and mesangial cells were investigated. Rat model of DC was induced by high fat feeding and injection of streptozotocin(STZ)of 25 mg·kg^-1. The DC rats were randomly divided into GP 300 mg·kg^-1,SBG 300 mg·kg^-1,GPSBG 600 mg·kg^-1 and DC model group. The investigation groups were respectively ig given corresponding extracts once daily for 8 weeks, while the controls and the models were given the same volume of sodium carboxy methyl cellulose (0.5%). The cardiac hemodynamic indexes and serum lipids were measured at 24 hours after the last administration. Result: SBG 5 mg·L^-1and GPSBG 5 mg·L^-1could compete the suppression of ECV-304 growth in 30 mmol·L^-1 glucose, increasing NO generation, reduce GSH levels, compete the inhibition of mesangial cell proliferation in 30 mmol·L^-1 glucose medium. SBG 5 mg·L^-1, GP 5 mg·L^-1 and GPSBG 5 mg·L^-1could compete the suppression of ECV-304 growth, increase NO generation, reduce GSH levels by H₂O₂ on myocardial cell. GP 300 mg·kg^-1and SBG 300 mg·kg^-1 could decrease the cardiac index in typeⅡdiabetic rats, GPSBG 600 mg·kg^-1 could significantly reduce the serum levels of TG and TC, index of heart in typeⅡdiabetic rats. GP 300 mg·kg^-1 could significantly increase left ventricular systolic blood pressure and heart rate, left ventricular end-diastolic pressure, the rate index of left ventricular contraction and relaxation time, and lower left ventricular end-diastolic pressure. SBG 300 mg·kg^-1could significantly reduce left ventricular end-diastolic pressure, GPSBG 600 mg·kg^-1 could significantly increase heart rate, left ventricular systolic blood pressure, left ventricular contraction and relaxation time rate, reduce left ventricular end-diastolic pressure in typeⅡdiabetic rats. Conclusion: GP and SBG show synergistic effect on improving cardiac function in typeⅡdiabetic rats. This may be related to the effects of GP and SBG on reducing serum TG, TC in typeⅡ diabetic rats, and their effects on endothelial cells, myocardial cells, mesangium cells and aldose reductase.