抵挡汤早期干预对2型糖尿病大鼠大血管病变的影响及其机制

Early intervention of Didang Decoction on macroangiopathy in type 2 diabetic rats and its mechanisms

目的观察抵挡汤早期干预对糖尿病大鼠大血管病变的影响及其机制。方法采用高脂饲料喂养及链尿佐菌素(STZ)诱导方法制备2型糖尿病大鼠模型,大鼠分成对照组,模型组,抵挡汤早期(给予STZ前4周给药)、中期(与STZ同时给药)及晚期(给予STZ后4周给药)干预组(每天均ig给予抵挡汤3.24 g/kg 1次),阳性药吡咯列酮(2.7 mg/kg)和辛伐他汀(1.8 mg/kg)组,各组给药至给予STZ后24周。免疫组化染色法观察大鼠主动脉细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)的表达,Western blotting法检测主动脉核因子-κB(NF-κB)及基质金属蛋白酶-9(MMP-9)蛋白表达。结果与模型组比较,抵挡汤早期和中期干预组、辛伐他汀组大鼠主动脉ICAM-1表达减少(P<0.05);抵挡汤早期干预组与辛伐他汀组主动脉VCAM-1表达减少(P<0.05);抵挡汤早期和中期干预组主动脉NF-κB及MMP-9蛋白表达明显降低(P<0.05),其中以抵挡汤早期干预组效果最显著。结论抵挡汤早期干预有效降低NF-κB调控的靶基因ICAM-1、VCAM-1及MMP-9蛋白表达,可能是其延缓2型糖尿病大鼠大血管病变发展的重要机制之一。

Objective To observe the effects of the early intervention with Didang Decoction （DDD） on macroangiopathy in type 2 diabetic rats. Methods The type 2 diabetic rat model was established using high-fat diet and Streptozotocin （STZ）, and the rats were divided into control, model, Pioglitazone （2.7 mg/kg）, Simvastatin （1.8 mg/kg）, early-, mid-, and late-term DDD-intervene groups （ig administered with 3.24 g/kg DDD once daily, before 4 weeks, at the same time, and after 4 weeks of STZ administration, respectively）, the rats in each group were administered until 24 weeks of STZ administration. The immunohistochemical and pathological changes of intercellular cell adhesion molecule- 1 （1CAM-l） and vascular cell adhesion molecule-1 （VCAM-1） in the aorta were observed, and the expression of nuclear factor-kappa B （NF-nB） and matrix metalloproteinases-9 （MMP-9） in aorta was detected using Western blotting. Results Compared with the model group, the ICAM-1 expression decreased in early- and mid-term DDD-intervene groups, and Simvastatin group （P 〈 0.05）, the VCAM-I expression decreased in early-term DDD-intervene and Simvastatin groups （P 〈 0.05）, the protein expression of NF-rd3 and MMP-9 was lower in early- and mid-term DDD-intervene groups （P 〈 0.05）, and it is the most obvious in early-term DDD-intervene group. Conclusion The contents of ICAM-1 and VCAM-1 as well as the protein expression of NF-r.B and MMP-9 in type 2 diabetic rats decrease after early-term DDD-intervene, which could regulate NF-rd3 signaling pathway to delay the development of diabetic macroangiopathy.