基于病证结合探讨血瘀证糖尿病肾病大鼠肾损害与内质网应激的关系

庞欣欣; 彭紫凝; 邢玉凤; 韩佳瑞; 孙新宇

doi:10.13422/j.cnki.syfjx.20202042

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基于病证结合探讨血瘀证糖尿病肾病大鼠肾损害与内质网应激的关系

药理 | 更新时间：2020-09-16

- 基于病证结合探讨血瘀证糖尿病肾病大鼠肾损害与内质网应激的关系
- Investigating Relationship Between Renal Damage and Endoplasmic Reticulum Stress in Diabetic Kidney Disease Rats with Blood Stasis Syndrome Based on Combination of Disease and Syndrome
- 中国实验方剂学杂志 2020年26卷第20期页码：74-81
- 作者机构：
  
  1.河南省中医院，郑州 450002
  2.河南中医药大学第二临床医学院，郑州 450046
- 作者简介：
  
  庞欣欣，博士，副主任医师，从事中医药治疗慢性肾脏病的研究，Tel：0371-60979837，E-mail：doctorpang@aliyun.com
  韩佳瑞，博士，副教授，从事中医药防治慢性肾脏病，Tel：0371-60979837，E-mail：HanJR2018@126.com
- 基金信息：
  
  国家中医临床研究基地科研项目(2019JDZX068);河南省高等学校重点科研计划项目(19A360009)
- DOI：10.13422/j.cnki.syfjx.20202042
  中图分类号： R2-0;R289;R587.1
- 收稿日期：2020-03-10，
  
  网络出版日期：2020-08-14，
  
  纸质出版日期：2020-10-20
- 稿件说明：
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庞欣欣,彭紫凝,邢玉凤等.基于病证结合探讨血瘀证糖尿病肾病大鼠肾损害与内质网应激的关系[J].中国实验方剂学杂志,2020,26(20):74-81.

PANG Xin-xin,PENG Zi-ning,XING Yu-feng,et al.Investigating Relationship Between Renal Damage and Endoplasmic Reticulum Stress in Diabetic Kidney Disease Rats with Blood Stasis Syndrome Based on Combination of Disease and Syndrome[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(20):74-81.
庞欣欣,彭紫凝,邢玉凤等.基于病证结合探讨血瘀证糖尿病肾病大鼠肾损害与内质网应激的关系[J].中国实验方剂学杂志,2020,26(20):74-81. DOI： 10.13422/j.cnki.syfjx.20202042.

PANG Xin-xin,PENG Zi-ning,XING Yu-feng,et al.Investigating Relationship Between Renal Damage and Endoplasmic Reticulum Stress in Diabetic Kidney Disease Rats with Blood Stasis Syndrome Based on Combination of Disease and Syndrome[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(20):74-81. DOI： 10.13422/j.cnki.syfjx.20202042.

摘要

目的

观察血瘀证对糖尿病肾病（DKD）大鼠的肾损害以及对内质网应激（ERS）的影响，探讨DKD血瘀证大鼠肾损害与ERS之间的关系。

方法

选用50只SPF级雄性SD大鼠，用高脂高糖饲料联合腹腔注射链脲佐菌素（STZ）方法建立DKD大鼠模型。随机分为正常组、糖尿病组、糖尿病+血瘀证组，其中糖尿病+血瘀证组（0.05 mg·kg

-1

）采用右旋糖酐法制备。观察各组大鼠一般情况、血液流变学指标，24 h尿蛋白含量、肌酐、肾脏病理学变化；免疫组化、蛋白免疫印迹法（Western blot）和实时荧光定量聚合酶链式反应（Real-time PCR）检测肾组织ERS相关蛋白葡萄糖调节蛋白78（GRP78），活化转录因子6（ATF6）和肾脏纤维化指标纤维连接蛋白（FN），

-平滑肌肌动蛋白（

-SMA）的mRNA及蛋白表达。

结果

与正常组比较，糖尿病组大鼠出现多饮多食多尿、体质量减轻，血液流变学指标全血黏度和血浆黏度均明显升高（

0.05，

0.01），24 h尿蛋白含量、肌酐、尿素氮显著上升（

0.01），肾脏病理加重，肾组织的GRP78，ATF6，FN和

-SMA的mRAN及蛋白表达明显升高（

0.05，

0.01）；经过右旋糖酐法制备血瘀证模型后，糖尿病+血瘀证组大鼠死亡率增加，体征变化较糖尿病组更加明显，全血黏度、血浆黏度，24 h尿蛋白含量、肌酐、尿素氮等较糖尿病组显著升高（

0.01），同时病理改变较糖尿病组加重，肾组织的GRP78，ATF6，FN，

-SMA的mRNA及蛋白表达较糖尿病组明显升高（

0.05，

0.01）。

结论

在病证结合模型下，血瘀证可能明显加重糖尿病肾病大鼠肾脏病理损害，且与增强糖尿病肾病大鼠肾脏组织的ERS有关。

Abstract

Objective

To observe the effect of blood stasis syndrome on renal damage and endoplasmic reticulum stress (ERS) in diabetic kidney disease (DKD) rats

and to explore the relationship between renal syndrome of blood stasis damage and ERS in DKD rats.

Method

The 50 Male SD rats of SPF level were selected to establish DKD rat model by high fat and high sugar diet combined with intra-abdominal injection of streptozotocin(STZ). They were randomly divided into normal group

diabetes mellitus group and diabetes mellitus and blood stasis syndrome group（0.05 mg·kg

-1

）

among which diabetes mellitus and blood stasis syndrome group was prepared by dextran method. The general conditions

hemorheology indexes

24 h urine protein

serum creatinine and renal pathology of the rats in each group were observed. Immunohistochemical analysis

Western blot and Real-time fluorescent quantitative polymerase chain reaction(Real-time PCR)were used to detect mRNA and protein expressions of endoplasmic reticulum stress-related proteins glucose regulated protein 78(GRP78)

activating transcription factor-6(ATF6) and renal fibrosis index fibronectin(FN)

and alpha smooth muscle actin(

-SMA).

Result

Compared with normal group

the rats in diabetes mellitus group showed polyphagia

polyuria and weight loss

increased hemorheology index of whole blood viscosity and plasma viscosity(

0.05，

0.01)

increased 24 h urine protein

serum creatinine and urea nitrogen(

0.01)

and increased renal pathology

and increased mRNA and protein expression of GRP78

ATF6

FN and

-SMA(

0.05，

0.01). After dextran preparation of blood stasis model. Diabetes mellitus and blood stasis syndrome group increased mortality

signs of change is more obvious in the diabetic group

whole blood viscosity

plasma viscosity

24 h urine protein ration

serum creatinine and urea nitrogen were significantly higher than those in diabetic rats(

0.01)

pathological changes aggravated in the diabetes group. At the same time， mRNA and protein expressions of GRP78

ATF6

and

-SMA in renal tissue were significantly higher than those in diabetic mellitus group(

0.05，

0.01).

Conclusion

Under the combined disease and syndrome model

the blood stasis syndrome may further aggravate the pathological damage of the kidney of DKD rats

and is related to the enhancement of ERS in the kidney of DKD rats.

关键词

Keywords

references

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