丹栝方干预糖尿病动脉粥样硬化大鼠糖脂代谢及氧化应激研究

作者	单位	E-mail
衡先培	福建中医药大学附属人民医院内分泌科（福州350004）	hengxianpei@hotmail.com
黄苏萍,程心玲,蓝元隆,杨柳清

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中文摘要:

目的探讨丹栝方对糖尿病动脉粥样硬化大鼠糖脂代谢及血清活性氧族（ROS）、胸主动脉核因子κB（nuclear factor kappa B，NF-κB）阳性表达及其 mRNA表达水平的影响，以揭示其干预糖尿病慢性并发症的部分机制。方法选取自发性糖尿病GK大鼠（Goto-Kakisaki Wistar rats）40只，以含代谢抑制剂丙硫氧嘧啶的高脂饲料饲养及内皮型一氧化氮合酶（NOS）抑制剂N-硝基-L-精氨酸甲酯腹腔注射，制备高脂糖尿病动脉硬化模型。将GK糖尿病成模鼠先按体重分层，再按血糖浓度根据随机数字表法分为丹栝方组［丹栝方，8 mL/（kg·d）］、二甲双胍组［二甲双胍，150 mg/（kg·d）］、辛伐他汀组［辛伐他汀，2 mg/（kg·d）］、模型组［纯净水，8 mL/（kg·d）］，每组各10只；另取同龄、体重可比Wistar大鼠10只作为正常对照组（正常组）。各组均灌胃干预24周。监测空腹血糖（FBG）、体重，测定HbA1c、TC、LDL-C、HDL-C、TG、血清ROS，免疫组化法分析主动脉NF-κB，Real-time PCR检测主动脉NF-κB（P65） mRNA表达。结果正常组体重最终显著超过其他各组（P<0.01），四组GK造模组间比较，差异无统计学意义。四组GK造模鼠全程FBG都高于正常组（P<0.01，P<0.05）；首次FBG、基线血糖各组间比较，差异无统计学意义（P>0.05），末次FBG二甲双胍组和丹栝方组都显著低于模型组（P<0.01）和辛伐他汀组（P<0.05）。干预24周后，四组GK造模鼠FBG、HbA1c、TC、LDL-C、 HDL-C、胸主动脉NF-κB的阳性表达率，及模型组、二甲双胍组、丹栝方组胸主动脉NF-κB mRNA的表达均高于正常组（P<0.01，P<0.05）；二甲双胍组、丹栝方组、辛伐他汀组TG、血清ROS，及辛伐他汀组胸主动脉NF-κB mRNA表达低于正常组（P<0.01，P<0.05）。药物干预三组FBG、TC、LDL-C、血清ROS、胸主动脉NF-κB mRNA的表达，丹栝方组、二甲双胍组胸主动脉NF-κB的阳性表达率，及丹栝方组HbA1c、TG显著低于模型组（P<0.01，P<0.05）。二甲双胍组、丹栝方组FBG低于辛伐他汀组（P<0.05）。辛伐他汀组、丹栝方组胸主动脉NF-κB mRNA的表达，及丹栝方组TC、LDL-C显著低于二甲双胍组（P<0.01）。结论丹栝方通过综合调节血糖、血脂，下调氧化应激，以发挥其防治糖尿病的慢性并发症作用。

英文摘要:

Objective To explore the effects of Dangua Recipe （DGR） on glycolipid metabolism， serum reactive oxygen species （ROS） level， nuclear factor kappa B （NF-κB） positive expression and its mRNA expression level in the thoracic aorta of diabetic rats with atherosclerosis， thus revealing its partial mechanisms for intervening chronic diabetic complications. Methods Recruited 40 Goto-Kakisaki （GK） Wistar rats were fed with high fat forage containing metabolic inhibition Propylthiouracil， and peritoneally injected with endothelial NOS inhibitor N-nitro-L-arginine methyl ester to establish a high fat diabetes model with atherosclerosis. The modeled GK rats were stratified by body weight， and then， by blood glucose level from high to low， randomly divided into the DGR group （at the daily dose of 8 mL/kg）， the metformin group （MET， at the daily dose of 150 mg/kg）， the simvastatin group （SIM， at the daily dose of 2 mg/kg）， and the model group （MOD， fed with pure water， at the daily dose of 8 mL/kg） according to the random number table， 10 in each group. Another 10 Wistar rats of the same ages and comparable body weight level were recruited as the normal control group. All the interventions lasted for 24 weeks by gastrogavage. The fasting blood glucose （FBG） and body weight were monitored. The HbA1c， TC， LDL-C， HDL-C， TG， serum ROS were determined. The aortic NF-κB level was analyzed with immunohistochemical assay. The expression of NF-κB （P65） mRNA in the aorta was detected with Real-time PCR. Results The body weight in the normal control group was eventually heavier than others （P<0.01）. There was no difference among the four groups of GK modeled rats （P>0.05）. The FBG in the four GK modeled groups were higher than that in the normal control group （P<0.01， P<0.05）. There was no statistical difference in the blood glucose level at the first visit and at the baseline among the GK modeled groups （P>0.05）. The last FBG level was obviously lower in the MET and DGR groups than in the MOD group （P<0.01） and the SIM group （P<0.05）. Twenty-four weeks after intervention， the level of FBG， HbA1c， TC， LDL-C， HDL-C， and NF-κB positive expression rate of the thoracic aorta of the four groups of GK modeled rats， and NF-κB mRNA expression in the thoracic aorta in the MOD group， the MET group， and the DGR group were significantly higher than those in the normal control group （P<0.01， P<0.05）. The TG level， serum ROS in the MET， DGR， and SIM groups， and the NF-κB mRNA expression level in the thoracic aorta in the SIM group were significantly lower than those in the normal control group （P<0.01， P<0.05）. The levels of FBG， TC， LDL-C， serum ROS， NF-κB mRNA expression level in the thoracic aorta in three drug intervention groups， and NF-κB positive expression rate in the DGR and MET groups， and the levels of HbA1c， TG in the DGR group were significantly lower than those in the MOD group （P<0.01， P<0.05）. The level of FBG in the MET and DGR groups were lower than that in the SIM group （P<0.05）. The level of NF-κB mRNA expression in the thoracic aorta of the SIM and DGR groups， and the levels of TC and LDL-C in the DGR group were significantly lower than those in the MET group （P<0.01）. Conclusion DGR played a role in preventing and treating chronic diabetic complications by comprehensively regulating blood glucose and serum lipids， as well as down-regulating oxidative stress.

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