Effect of Compound Danshen Dropping Pills on Heart of Diabetic Cardiomyopathy Rats by Regulating VEGF/TGF-β<sub>1</sub> by miRNA-200b

Ya-wen FAN; Li-chang LIANG; Tian-feng ZHANG; Lei MU; Tian XIE; Xiao-bing JIANG; Hui REN

doi:10.13422/j.cnki.syfjx.20191606

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Effect of Compound Danshen Dropping Pills on Heart of Diabetic Cardiomyopathy Rats by Regulating VEGF/TGF-β₁ by miRNA-200b

Pharmacology | 更新时间：2021-02-09

- Effect of Compound Danshen Dropping Pills on Heart of Diabetic Cardiomyopathy Rats by Regulating VEGF/TGF-β₁ by miRNA-200b
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 17, Pages: 34-42(2019)
- 作者机构：
  
  1.广州中医药大学　深圳医院(福田)，广东　深圳　 518034；
  2.广州中医药大学　第一附属医院，广州　 510405
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191606
  CLC： R2-0; R22; R285.5; R289
- Received：24 February 2019，
  
  Published Online：06 May 2019，
  
  Published：05 September 2019
- 稿件说明：
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Ya-wen FAN, Li-chang LIANG, Tian-feng ZHANG, et al. Effect of Compound Danshen Dropping Pills on Heart of Diabetic Cardiomyopathy Rats by Regulating VEGF/TGF-β₁ by miRNA-200b[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(17): 34-42.
DOI：

Ya-wen FAN, Li-chang LIANG, Tian-feng ZHANG, et al. Effect of Compound Danshen Dropping Pills on Heart of Diabetic Cardiomyopathy Rats by Regulating VEGF/TGF-β₁ by miRNA-200b[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(17): 34-42. DOI： 10.13422/j.cnki.syfjx.20191606.

摘要

目的：

研究复方丹参滴丸对2型糖尿病心肌病大鼠心脏的保护作用及机制。

方法：

将75只雄性SD大鼠随机分为正常组(15只)，和造模组(60只)，造模组用高糖高脂饲料＋高糖高脂乳制＋蔗糖水三联法喂养，6周后选择符合食源性肥胖(体质量≥正常组体质量均值＋2倍标准差)的大鼠，予以单次腹腔注射1%链脲佐菌素(STZ)28 mg·kg

－1

，12周后将空腹血糖≥11.1 mmol·L

－1

，且有多饮、多尿、多食、体质量减轻等现象的大鼠随机分为模型组、复方丹参滴丸组(0.5 g·kg

－1

)和二甲双胍组(0.5 g·kg

－1

)，连续干预12周。实验末采用超声心动图评价心功能。取血测定大鼠相应生化指标。苏木素-伊红(HE)和马松(Masson)染色观察心肌组织病理变化。电镜下观察心肌组织超微结构。蛋白免疫印迹法(Western blot)检测血管内皮生长因子(VEGF)，转化生长因子-

(TGF-

)和Ⅰ型胶原(Collagen Ⅰ)蛋白的表达。实时荧光定量聚合酶链式反应(Real-time PCR)检测miR-200b mRNA的表达。

结果：

与正常组比较，模型组大鼠心脏质量指数(HMI)，空腹血糖(FBG)，糖化血红蛋白(HbA1c)，空腹胰岛素(FINS)，总胆固醇(TC)，甘油三脂(TG)，低密度脂蛋白胆固醇(LDL-C)水平明显升高(

0.05，

0.01)，高密度脂蛋白胆固醇(HDL-C)水平显著降低(

0.01)；心功能受损，心肌胶原纤维沉积增加(

0.01)，心肌组织破坏程度明显；心肌组织中miR-200b mRNA表达显著降低(

0.01)，VEGF，TGF-

和Collagen Ⅰ蛋白表达显著升高(

0.01)。与模型组比较，复方丹参滴丸组大鼠HMI，TC，TG，LDL-C水平明显下降(

0.05，

0.01)，HDL-C水平显著升高(

0.01)；心功能得到改善，心肌胶原纤维沉积明显减少(

0.05)，心肌组织破坏程度减轻；心肌组织中miR-200b mRNA表达明显升高(

0.05)，VEGF，TGF-

和Collagen Ⅰ蛋白表达明显降低(

0.05，

0.01)。

结论：

复方丹参滴丸可能是通过降脂，上调miR-200b的表达并抑制VEGF，TGF-

，Collagen Ⅰ的表达水平，对2型糖尿病心肌病大鼠的心脏起保护作用。

Abstract

Objective:

To study the protective effect and mechanism of compound Danshen dropping pills on the heart of rats with type 2 diabetic cardiomyopathy.

Method:

Seventy-five male SD rats were randomly divided into blank group (15 rats) and model group (60 rats). The model group was fed with high-sugar and high-fat diet

high-sugar and high-fat milk and sucrose water. Six weeks later

rats with foodborne obesity (body mass ≥ the mean body mass of blank control group + 2 times standard deviation) were selected and intraperitoneally injected with 1% streptozotocin (STZ)28 mg·kg

-1

. After 12 weeks

rats with fasting blood glucose ≥ 11.1 mmol·L

-1

and polydipsia

diuresis

polyphagia and weight loss were randomly divided into model group

compound Danshen dropping pills group (0.5 g·kg

-1

) and metformin group (0.5 g·kg

-1

) and intervened for 12 weeks. At the end of the experiment

echocardiography was used to evaluate cardiac function. Blood samples were taken to determine the corresponding biochemical indicators of rats. Histopathological changes of myocardium were observed by hematoxylin-eosin (HE) and Masson staining. The ultrastructure of myocardium was observed under electron microscope. Western blot was used to detect the expressions of vascular endothelial growth factor (VEGF)

transforming growth factor-beta 1 (TGF-

) and type Ⅰ collagen (Collagen Ⅰ). Real-time fluorescence quantitative analysis (Real-time PCR) was used to detect the expression of miRNA-200b.

Result:

Compared with the blank group

the heart weight index (HMI)

fasting blood glucose (FBG)

glycosylated hemoglobin (HbA1c)

fasting insulin (FINS)

total cholesterol (TC)

triglyceride (TG)

low-density lipoprotein cholesterin(LDL-C) levels in the model group were significantly increased (

0.05

0.01)

while the levels of high-density lipoprotein cholesterin(HDL-C) decreased significantly (

0.01); the cardiac function was impaired

the deposition of collagen fibers increased (

0.01)

and the degree of myocardial tissue damage was obvious; the expression of miR-200b in myocardial tissue decreased (

0.01)

and the expressions of VEGF

TGF-

and Collagen I increased (

0.01). Compared with the model group

the levels of HMI

TG and LDL-C in the compound Danshen dropping pills group were significantly increased (

0.05

0.01)

and the levels of HDL-C increased significantly (

0.01)

the cardiac function was improved

the deposition of collagen fibers in myocardium was decreased (

0.05)

the degree of myocardial tissue damage was reduced

the expression of miRNA-200b in myocardium was increased (

0.05)

and the expressions of VEGF

TGF-

and Collagen I was decreased (

0.05

0.01).

Conclusion:

Compound Danshen dropping pills may play a protective role in the heart of type 2 diabetic cardiomyopathy rats by lowering lipid

up-regulating the expression of miR-200b and inhibiting the expression levels of VEGF

TGF-

and Collagen I.

关键词

Keywords

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⁰

Effect of Compound Danshen Dropping Pills on Heart of Diabetic Cardiomyopathy Rats by Regulating VEGF/TGF-β1 by miRNA-200b

DOI：10.13422/j.cnki.syfjx.20191606

摘要

Abstract

关键词

Keywords

references

Effect of Compound Danshen Dropping Pills on Heart of Diabetic Cardiomyopathy Rats by Regulating VEGF/TGF-β₁ by miRNA-200b