Effect of Puerarin Combined with Tanshinone Ⅱ<sub>A</sub> on t-PA, PAI-1 and Oxidative Stress in DM Rats with Vascular Lesions

Xue YANG; Fei ZHOU; Yang YANG; Chao-li LUO; Wen-tao HUANG; Xian-qin LUO; Xiao-ming ZHONG; Heng-hua LI

doi:10.13422/j.cnki.syfjx.20191905

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Effect of Puerarin Combined with Tanshinone Ⅱ_A on t-PA, PAI-1 and Oxidative Stress in DM Rats with Vascular Lesions

Pharmacology | 更新时间：2021-02-09

- Effect of Puerarin Combined with Tanshinone Ⅱ_A on t-PA, PAI-1 and Oxidative Stress in DM Rats with Vascular Lesions
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 19, Pages: 46-54(2019)
- 作者机构：
  
  1.重庆市中药研究院　重庆市药物安全评价中心，重庆　 400065；
  2.浙江中医药大学　药学院，杭州　 310053
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191905
  CLC： R2-0; R22; R285.5
- Received：24 March 2019，
  
  Published Online：19 June 2019，
  
  Published：05 October 2019
- 稿件说明：
移动端阅览
Xue YANG, Fei ZHOU, Yang YANG, et al. Effect of Puerarin Combined with Tanshinone Ⅱ_A on t-PA, PAI-1 and Oxidative Stress in DM Rats with Vascular Lesions[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(19): 46-54.
DOI：

Xue YANG, Fei ZHOU, Yang YANG, et al. Effect of Puerarin Combined with Tanshinone Ⅱ_A on t-PA, PAI-1 and Oxidative Stress in DM Rats with Vascular Lesions[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(19): 46-54. DOI： 10.13422/j.cnki.syfjx.20191905.

摘要

目的：

观察葛根素联合丹参酮Ⅱ

对糖尿病血管病变大鼠的保护作用及其相关机制。

方法：

高脂饲料喂养SD大鼠给予尾静脉注射链脲佐菌素(STZ)制作糖尿病血管病变模型，将造模成功大鼠随机分为模型组，葛根素联合丹参酮Ⅱ

高(0.5 g·kg

－1

＋1.0 g·kg

－1

)，中(0.25 g·kg

－1

＋0.5 g·kg

－1

)，低剂量组(0.05 g·kg

－1

＋0.1 g·kg

－1

)，丹参酮Ⅱ

(0.5 g·kg

－1

)组，葛根素(0.25 g·kg

－1

)组，二甲双胍药(二甲双胍，0.09 g·kg

－1

)组，每组10只，连续灌胃给药70 d。观察实验各组药物干预后大鼠体质量及一般情况；采用全自动生化分析仪检测大鼠血糖、血脂含量；采用酶联免疫吸附测定(ELISA)检测大鼠血清胰岛素(INS)，晚期糖基化终末产物(AGEs)，超氧化物歧化酶(SOD)，谷胱甘肽过氧化物酶(GSH-Px)含量，血浆组织纤溶酶原激活物(t-PA)，纤溶酶原激活物抑制物-1(PAI-1)，血栓素B

(TXB

)含量，主动脉匀浆AGEs，氧化型低密度脂蛋白(ox-LDL)含量；采用化学比色法检测大鼠血清丙二醛(MDA)含量；苏木素-伊红(HE)染色观察冠状动脉组织病理学改变；免疫组化观察主动脉PAI-1蛋白表达。

结果：

与正常组比较，模型组血糖及血脂明显升高(

0.05，

0.01)，血清INS，AGEs，MDA含量明显增加(

0.05，

0.01)，血浆PAI-1，TXB

含量显著增加(

0.01)，主动脉匀浆AGEs，ox-LDL含量显著增加(

0.01)，血清SOD，GSH-Px水平显著降低(

0.01)，血浆t-PA含量明显降低(

0.05)，主动脉组织PAI-1蛋白表达明显增加(

0.05)；与模型组比较，葛根素联合丹参酮 Ⅱ

可降低血糖及血脂水平(

0.05，

0.01)，降低血清INS，AGEs，MDA含量(

0.05，

0.01)，降低血浆PAI-1，TXB

含量(

0.05，

0.01)，降低主动脉匀浆AGEs，ox-LDL含量(

0.05，

0.01)，升高血清SOD，GSH-Px含量(

0.05，

0.01)，升高血浆t-PA含量(

0.05，

0.01)，减轻冠状动脉组织病变，降低主动脉组织PAI-1蛋白表达(

0.05)，其效果好于单药。

结论：

葛根素联合丹参酮Ⅱ

能减轻糖尿病大鼠血管病变，其机制可能与减轻氧化应激，调节凝血-纤溶系统有关。

Abstract

Objective:

To observe the protective effect and mechanism of combination of puerarin combined with tanshinone Ⅱ

on diabetes mellitus (DM) rats with vascular lesions.

Method:

The SD rats (fed with high-fat diet) were administrated with streptozotocin(STZ) through intravenous injection to make the model of diabetic vascular lesions. The successfully modeled rats were randomly divided into the model control group

the high-dose group (0.5 g·kg

-1

+ 1.0 g·kg

-1

)

the middle-dose group (0.25 g·kg

-1

+ 0.5 g·kg

-1

)

the low-dose group (0.05 g·kg

-1

+ 0.1 g·kg

-1

)

the puerarin group (0.25 g·kg

-1

)

the tanshinone Ⅱ

group (0.5 g·kg

-1

) and the positive control group (Metformin

0.09 g·kg

-1

). Each group was administrated with drugs respectively by gavage for 70 days. After intervention in each group

the general conditions and body weight of the rats were observed. The contents of blood grucose and blood lipids were determined by automatic biochemical analyzer. The contents of insulin

advanced glycation end products (AGEs)

superoxide dismutase(SOD)

glutathione peroxidase (GSH-Px) in serum

the contents of tissue plasminogen activator (t-PA)

plasminogen activator inhibitor-1 (PAI-1) and thromboxane B

(TXB

) in plasma

as well as the contents of AGEs and oxidized low-density lipoprotein(ox-LDL) in aorta homogenate were detected by enzyme-linked immunosorbent assay(ELISA). The content of malondialdehyde(MDA) in serum was determined by chemical colorimetry. Pathological changes of coronary tissue were observed by htoxylin eosin(HE) staining. The expression of PAI-1 protein of aorta was observed by immunohistochemistry.

Result:

Compared with the normal control group

in the model group

the levels of blood grucose and blood lipids (

0.05

0.01)

the contents of insulin

AGEs and MDA in serum (

0.05

0.01)

the contents of PAI-1 and TXB

in plasma (

0.01)

and the contents of AGEs and ox-LDL in aorta homogenate were increased(

0.01). The contents of SOD and GSH-Px in serum (

0.01)

the contents of t-PA in plasma were decreased(

0.05)

whereas the expression of PAI-1 protein of aorta was increased (

0.05). Compared with the model group

in the drug intervention group

the levels of blood grucose and blood lipids (

0.05

0.01)

the contents of insulin

AGEs and MDA in serum (

0.05

0.01)

the contents of PAI-1 and TXB

in plasma (

0.05

0.01)

and the contents of AGEs and ox-LDL in aorta homogenate were decreased(

0.05

0.01)

whereas the contents of SOD and GSH-Px in serum and the contents of t-PA in plasma were increased(

0.05

0.01). The coronary lesions were relieved

and the expression of PAI-1 protein of aorta was reduced (

0.05). The efficacy of combined medication was better than single drug administration.

Conclusion:

Puerarin combined with Tanshinone Ⅱ

could relieve vascular lesions of DM rats. The mechanisms may be related to the reduction of oxidative stress and the regulation of coagulation-fibrinolysis system.

关键词

Keywords

references

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⁰

Effect of Puerarin Combined with Tanshinone ⅡA on t-PA, PAI-1 and Oxidative Stress in DM Rats with Vascular Lesions

DOI：10.13422/j.cnki.syfjx.20191905

摘要

Abstract

关键词

Keywords

references

Effect of Puerarin Combined with Tanshinone Ⅱ_A on t-PA, PAI-1 and Oxidative Stress in DM Rats with Vascular Lesions