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[当归方对动脉粥样硬化糖尿病大鼠糖脂代谢及氧化应激的干预研究]

[Research of Dangua Recipe on intervening the glycolipid metabolism and oxidative stress in diabetic rats with atherosclerosis].

作者信息

Heng Xian-Pei, Huang Su-Ping, Cheng Xin-Iing, Lan Yuan-Long, Yang Liu-Qing, Pan Xu-Dong, Ling Chen, Lin Jiu-Mao, Li Peng-Hui, Wu Jing, Lin Miao-Xian, Chen Min-Ling, Xie Yu, Guo Fang, Ding Zong-Ping, Lei Ying

机构信息

Department of Endocrinology, People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou (350004), China.

出版信息

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2013 Feb;33(2):244-51.

PMID:23646483
Abstract

OBJECTIVE

To explore the effects of Dangua Recipe (DGR) on glycolipid metabolism, serum reactive oxygen species (ROS) level, nuclear factor kappa B (NF-kappaB) 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-kappaB level was analyzed with immunohistochemical assay. The expression of NF-kappaB (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-kappaB positive expression rate of the thoracic aorta of the four groups of GK modeled rats, and NF-kappaB 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-kappaB 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-kappaB mRNA expression level in the thoracic aorta in three drug intervention groups, and NF-kappaB 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-kappaB 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.

摘要

目的

探讨瓜蒌方(DGR)对动脉粥样硬化糖尿病大鼠糖脂代谢、血清活性氧(ROS)水平、核因子κB(NF-κB)阳性表达及其在胸主动脉中mRNA表达水平的影响,从而揭示其干预慢性糖尿病并发症的部分机制。

方法

选取40只Goto-Kakisaki(GK)Wistar大鼠,用含代谢抑制剂丙基硫氧嘧啶的高脂饲料喂养,并腹腔注射内皮型一氧化氮合酶抑制剂N-硝基-L-精氨酸甲酯,建立伴有动脉粥样硬化的高脂糖尿病模型。将造模成功后的GK大鼠按体重分层,再按血糖水平从高到低,根据随机数字表随机分为DGR组(每日剂量8 mL/kg)、二甲双胍组(MET,每日剂量150 mg/kg)、辛伐他汀组(SIM,每日剂量2 mg/kg)和模型组(MOD,给予纯水,每日剂量8 mL/kg),每组10只。另选取10只年龄相同、体重水平相近的Wistar大鼠作为正常对照组。所有干预均通过灌胃持续24周。监测空腹血糖(FBG)和体重。测定糖化血红蛋白(HbA1c)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)、血清ROS。用免疫组织化学法分析主动脉NF-κB水平。用实时荧光定量聚合酶链反应检测主动脉中NF-κB(P65)mRNA的表达。

结果

正常对照组最终体重比其他组重(P < 0.01)。四组GK造模大鼠之间无差异(P > 0.05)。四组GK造模大鼠的FBG均高于正常对照组(P < 0.01,P < 0.05)。GK造模组首次就诊时和基线时血糖水平无统计学差异(P > 0.05)。MET组和DGR组末次FBG水平明显低于MOD组(P < 0.01)和SIM组(P < 0.05)。干预24周后,四组GK造模大鼠的FBG、HbA1c、TC、LDL-C、HDL-C水平以及胸主动脉NF-κB阳性表达率,MOD组、MET组和DGR组胸主动脉中NF-κB mRNA表达均显著高于正常对照组(P < 0.01,P < 0.05)。MET组、DGR组和SIM组的TG水平、血清ROS以及SIM组胸主动脉中NF-κB mRNA表达水平均显著低于正常对照组(P < 0.01,P < 0.05)。三个药物干预组的FBG、TC、LDL-C水平、胸主动脉中血清ROS、NF-κB mRNA表达水平以及DGR组和MET组的NF-κB阳性表达率,DGR组的HbA1c、TG水平均显著低于MOD组(P < 0.01,P < 0.05)。MET组和DGR组的FBG水平低于SIM组(P < 0.05)。SIM组和DGR组胸主动脉中NF-κB mRNA表达水平以及DGR组的TC和LDL-C水平均显著低于MET组(P < 0.01)。

结论

DGR通过全面调节血糖和血脂以及下调氧化应激在防治慢性糖尿病并发症中发挥作用。

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