黄杞总黄酮对2型糖尿病合并动脉粥样硬化大鼠主动脉损伤的保护作用

Protective effects of total flavonoids from Engelhardtia roxburghiana on aorta injury in rats with type 2 diabetes and complication of atherosclerosis

目的探讨黄杞总黄酮对2型糖尿病合并动脉粥样硬化大鼠主动脉损伤的保护作用。方法高脂饲料结合腹腔注射N-硝基-L-精氨酸甲酯(5 mg/kg)诱导GK大鼠动脉粥样硬化后,将其随机分为5组,模型组,二甲双胍组,阿托伐他汀组,黄杞总黄酮高、低剂量组,以Wistar大鼠为正常对照组。各组(除模型组和正常对照组外)大鼠分别灌胃给予二甲双胍(150 mg/kg)、阿托伐他汀(10 mg/kg)、黄杞总黄酮(500、250 mg/kg),持续8周,检测空腹血糖、HDL、LDL、TG、TC水平。然后,离体主动脉环灌流法评价黄杞总黄酮对离体胸主动脉舒缩功能的影响,HE染色、Masson染色观察主动脉病理变化,Real-time PCR法检测主动脉NF-κB p65、ICAM-1 mRNA表达。结果黄杞总黄酮降低空腹血糖、LDL、TG、TC水平,抑制去甲肾上腺素介导的主动脉收缩,改善主动脉损伤,下调NF-κB p65、ICAM-1 mRNA表达,差异均有统计学意义(P<0.05,P<0.01)。结论黄杞总黄酮可通过抑制主动脉收缩和NF-κB信号通路、降低炎性因子表达来对2型糖尿病合并动脉粥样硬化大鼠主动脉损伤起到保护作用。

AIM To investigate the protective effects of total flavonoids from Engelhardtia roxburghiana Wall.（TFER） on aorta injury in rats with type 2 diabetes and complication of atherosclerosis. METHODS GK rats fed with high fat diet were intraperitoneally injected with N-nitro-L-arginine-methyl ester hydrochloride（5 mg/kg） to induce atherosclerosis,which were then randomly divided into five groups,model group,metformin group,atorvastatin group,high-dose TFER group and low-dose TFER group,Wistar rats were taken as normal control group. The rats in the various groups（ except for the model group and the normal control group） were given 8-week intragastrical administration of metformin（150 mg/kg）,atorvastatin（10 mg/kg）,TFER（500,250 mg/kg）,respectively,after which fasting blood glucose,HDL,LDL,TG,TC levels were measured. Then the effect of TFER on diastolic and systolic function of isolated thoracic aorta was evaluated by isolated vascular perfusion method,the pathologic changes of thoracic aorta were observed by HE staining and Masson staining,and the mRNA expressions of NF-κB p65 and ICAM-1 in thoracic aorta were detected by real time-PCR. RESULTS TFER decreased fasting blood glucose,LDL,TG,TC levels,inhibited aorta contraction induced by norepinephrine,improved aorta injury,and down-regulated the mRNA expressions of NF-κB p65 and ICAM-1. All the differences had statistical significances（P 〈 0. 05,P 〈 0. 01）. CONCLUSION TFER can exhibit protective effects on aorta injury in rats with type 2 diabetes and complication of atherosclerosis by inhibiting aorta contraction and NF-κB signal pathway,and decreasing expressions of inflammatory factors.