补肾益气化浊通络法对糖尿病肾病小鼠肾脏细胞外基质的影响

史晓伟; 张定华; 罗向霞; 刘怡; 裴文丽; 张东鹏; 李继文; 谢卓霖; 马如龙

doi:10.13422/j.cnki.syfjx.20180792

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补肾益气化浊通络法对糖尿病肾病小鼠肾脏细胞外基质的影响

药理 | 更新时间：2024-01-04

- 补肾益气化浊通络法对糖尿病肾病小鼠肾脏细胞外基质的影响
- Effect of Bushen Yiqi Huazhuo Tongluo Method on Renal Extracellular Matrix of Diabetic Nephropathy Mice
- 中国实验方剂学杂志 2018年24卷第7期页码：114-120
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金项目（81460699）;国家中医药管理局国家中医临床研究基地业务建设科研专项（JDZX2015）;甘肃省自然科学基金项目（1308RJZA202）
- DOI：10.13422/j.cnki.syfjx.20180792
  中图分类号： R285.5
- 纸质出版日期：2018
- 稿件说明：
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史晓伟, 张定华, 罗向霞, 等. 补肾益气化浊通络法对糖尿病肾病小鼠肾脏细胞外基质的影响[J]. 中国实验方剂学杂志, 2018,24(7):114-120.

SHI Xiao-wei, ZHANG Ding-hua, LUO Xiang-xia, et al. Effect of Bushen Yiqi Huazhuo Tongluo Method on Renal Extracellular Matrix of Diabetic Nephropathy Mice[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(7): 114-120.
史晓伟, 张定华, 罗向霞, 等. 补肾益气化浊通络法对糖尿病肾病小鼠肾脏细胞外基质的影响[J]. 中国实验方剂学杂志, 2018,24(7):114-120. DOI： 10.13422/j.cnki.syfjx.20180792.

SHI Xiao-wei, ZHANG Ding-hua, LUO Xiang-xia, et al. Effect of Bushen Yiqi Huazhuo Tongluo Method on Renal Extracellular Matrix of Diabetic Nephropathy Mice[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(7): 114-120. DOI： 10.13422/j.cnki.syfjx.20180792.

摘要

目的：探讨补肾益气化浊通络法对2型糖尿病肾病db/db小鼠肾脏细胞外基质（extracellular matrix，ECM）的影响。方法：以具有补肾益气化浊通络作用的科研协定方糖肾康（Tangshenkang，TSK）为研究药物，将100只12周龄SPF级雄性db/db小鼠随机分为5组，模型组，罗格列酮组，糖肾康低、中、高剂量组（4.6，13.8，41.4 g · kg-1），另将20只SPF级SD大鼠设为空白组。各组连续灌胃12周后采血，并留取肾脏组织。全自动生化仪检测甘油三酯（triglycerides，TG），总胆固醇（total cholesterol，TC），高密度脂蛋白胆固醇（high density lipoprotein cholesterol，HDL-C），低密度脂蛋白胆固醇（low density lipoprotein cholesterol，LDL-C），血清胱抑素-C（serum cystatin-C，Cys-C），肌酐清除率（creatinine clearance rate，CCr）；免疫组化法检测纤维连接蛋白（fibronectin，FN），层粘连蛋白（laminin，LN），胶原（collagen，Col），α-平滑肌肌动蛋白（alpha-smooth muscle actin，α-SMA），转换生长因子（transforming growth factor，TGF）-β和T细胞群集分化抗原8+（cluster of differentiation 8+，CD8+）。结果：治疗后，TSK中、高剂量小鼠体质量明显降低（P<0.01）；在第8周，TSK各剂量组小鼠的随机血糖均明显降低，TSK高剂量组降糖效果持续（P<0.05，P<0.01）；TSK中、高剂量组TG，TC，LDL-C，Cys-C均明显下降，CCr，HDL-C上升（P<0.05，P<0.01）；TSK各剂量组ECM（FN，LN，ColⅢ和ColⅣ），α-SMA，TGF-β和CD8+显著降低（P<0.05，P<0.01），且呈剂量依赖性。结论：TSK通过减少α-SMA，TGF-β和CD8+在DN小鼠肾脏的表达，降低DN小鼠体质量，改善血脂代谢及肾功能，降低肾脏组织ECM沉积，减轻了肾小球硬化和肾间质纤维化程度，这可能是补肾益气化浊通络法治疗DN的机制之一。

Abstract

Objective: To explore the effect of Bushen Yiqi Huazhuo Tongluo method on renal cell extracellular matrix (ECM) in mice with type 2 diabetic nephropathy (db/db). Method: Tangshenkang(TSK)with the functions of tonifying kidney

replenishing Qi

clearing turbidity and dredging collaterals as the research drug.The 100 SPF male db/db mice at 12 weeks old were randomly divided into 5 groups

namely model control group

rosiglitazone (positive control) group

TSK high

medium and low-dose groups (TH

4.6

13.8

41.4 g · kg-1). Another 20 SPF SD rats were used as blank control group.After 12 weeks of continuous gastric administration

the blood and the kidney tissueswere taken.Triglycerides (TG)

total cholesterol(TC)

high-density lipoprotein cholesterol (HDL-C)

low density lipoprotein cholesterol (LDL-C)

serum cystatin-C (Cys-C) and creatinine clearance (CCr) levels were detected by automatic biochemistry analyzer; and the levels of fibronectin (FN)

laminin (LN)

collagen (Col) and alpha-smooth muscle actin (α-SMA)

transforming growth factor(TGF)-β and cluster of differentiation 8+(CD8+) were detected by immunohistochemical method. Result: After treatment

the body weight was significantly decreased in TM group and TH group(P<0.01).In week 8

the random blood glucose of the mice in TSK groups was significantly reduced

and the hypoglycemic effect was still present in TH group (P<0.05

P<0.01).The TG

LDL-C

Cys-C levels of TM group and TH group were all significantly reduced

CCr and HDL-C was increased (P<0.05

P<0.01);ECM(FN

Col Ⅲ and Col Ⅳ)

α-SMA

TGF-β and CD8+ of TSK groups were significantly reducedin a dose-dependent manner. Conclusion: TSK had reduced the degree of glomerular sclerosis and renal interstitial fibrosis

by reducing the expression of α-SMA

TGF-β and CD8+ in DN mice kidney

lowering the weight of DN mice

improving blood lipid metabolism and renal function

and reducing kidney tissue ECM deposition.This may be one of the mechanisms for the treatment of DN by the method of Bushen Yiqi Huazhuo Tongluo method.

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