玉泉丸防治糖尿病慢性并发症的作用机理研究

Study on the mechanism of Yuquan pill on prevention of diabetic chronic complications

目的:探讨玉泉丸对2型糖尿病的防治作用及可能的作用机理。方法:新生大鼠自出生第二天起颈部皮下注射L谷氨酸钠(MSG)5g.kg-1隔天一次,共三次,诱导肥胖大鼠胰岛素抵抗模型,8w后将其分为空白对照组,模型组,玉泉丸3.0、6.0、12.0g.kg-1组及阳性对照(罗格列酮)组,运用正糖钳技术测定胰岛素敏感性,ELISA法测定大鼠的胰岛素水平,考察玉泉丸对胰岛素抵抗的影响;运用高脂膳食加腹腔注射链脲佐菌素(Streptozotocin,STZ)20mg.kg-1复制Ⅱ型糖尿病大鼠模型,分为空白对照组,模型组,玉泉丸3.0、6.0、12.0g.kg-1组及阳性对照(罗格列酮)组,考察玉泉丸对血液脂质等指标的影响。结果:(1)与对照组相比,MSG模型大鼠血糖水平明显升高,Lee′s指数及胰岛素水平明显升高,葡萄糖输注速率(Glucose infusion rate,GIR)显著降低;与MSG模型大鼠相比,玉泉丸3.0g.kg-1可显著降低MSG模型大鼠血糖水平,玉泉丸各剂量组均可显著增加MSG模型大鼠GIR。(2)与对照组相比,STZ诱导的2型糖尿病大鼠血清TG、TC、HDL显著升高,经玉泉丸3.0g.kg-1治疗可显著降低血清TC以及LDL水平,而玉泉丸6.0g.kg-1可显著降低Ⅱ型糖尿病大鼠血清TC、HDL以及LDL水平。结论:玉泉丸一方面可通过改善胰岛素敏感性发挥其防治糖尿病慢性并发症的作用,另一方面也可通过调节血脂代谢改善糖尿病患者大血管病变以及微血管病变,为临床应用该药以改善糖尿病慢性并发症提供了一定的实验依据,其详细作用机理有待进一步研究。

Objective.. To investigate the effects and mechanism of Yuquan pill on type Ⅱ-diabetes mellitus. Methods.. The neonatal rats were subcutaneous injection of monosodium glutamate （MSG） 5 g ·kg^-1 every other day, for three times, to induce obesity. Eight weeks and then divided into the model group, Yuquan pill 3.0, 6. 0 and 12. 0 g ·kg^-1, positive control group （Rosiglitazone）, and normal control group. To study the effect of Yuquan pill on insulin resistance, the glucose clamp technique was used to check the insulin sensitivity index, the blood insulin concentration was detected by ELISA. To evaluate the effect of Yuquan pill on blood lipid, the type 2-diabetic rats were induced by high-fat diet and intraperitoneal injection of streptozotocin （STZ） 20 mg·kg^-1.Divided into the model group, Yuquan pill 3. 0, 6.0 and 12. 0 g·kg^-1 , positive control group （Rosiglitazone）, and normal control group. Results.. （1） Compared with normal control rats, Leers index, levels of insulin and glucose in serum were significantly higher, and GIR （Glucose infusion rate） was lower in MSG rats. Yuquan pill 3. 0 g ·kg^-1 can decrease glucose level, and Yuquan pill 3.0,6. 0 and 12. 0 g ·kg^-1 can significantly increase GIR, as compared to MSG rats. （2） Compared with normal control rats, the serum levels of TG, TC, and HDL were significantly increased in the type Ⅱ-diabetic rats. Yuquan pill 3. 0 g ·kg^-1 significantly decreased the levels of TC, LDL, and Yuquan pill 6. 0 g·kg^-1 reduced significantly the levels of TC, HDL and LDL levels in serum, as compared to MSG rats. Conclusion： The results suggest that the effects of Yuquan pill on diabetic chronic complications may be related to improve insulin sensitivity and regulate blood lipid metabolism improving diabetics＇ vascular complication and microangiopathy. The detailed mechanism needs further research.