Early Intervention of Didang Decoction on MLCK Signaling Pathways in Vascular Endothelial Cells of Type 2 Diabetic Rats.

Shoujiao Ye,Zhenqiang Song,Jing Li,Juhong Yang,Bai Chang,Chunshen Li

doi:10.1155/2016/6704851

Shoujiao Ye, Zhenqiang Song + Show 4 more

Open Access

https://doi.org/10.1155/2016/6704851

Copy DOI

Abstract

In the study, type 2 diabetic rat model was established using streptozotocin (STZ) combined with a high-fat diet, and the rats were divided into control and diabetic groups. Diabetic groups were further divided into nonintervening, simvastatin, Didang Decoction (DDD) early-phase intervening, DDD mid-phase intervening, and DDD late-phase intervening groups. The expression level of MLCK was detected using Western Blot analysis, and the levels of cyclic adenosine monophosphate (cAMP), protein kinase C (PKC), and protein kinase A (PKA) were examined using Real Time PCR. Under the electron microscope, the cells in the early-DDD-intervention group and the simvastatin group were significantly more continuous and compact than those in the diabetic group. Compared with the control group, the expression of cAMP-1 and PKA was decreased in all diabetic groups, whereas the expression of MLCK and PKC was increased in early- and mid-phase DDD-intervening groups (P < 0.05); compared with the late-phase DDD-intervening group, the expression of cAMP-1 and PKA was higher, but the level of MLCK and PKC was lower in early-phase DDD-intervening group (P < 0.05). In conclusion, the early use of DDD improves the permeability of vascular endothelial cells by regulating the MLCK signaling pathway.

Highlights

Diabetic macrovascular complications are the leading cause of death and disability causing 70–80% of deaths in diabetic patients [1]
This study investigated the effect of early intervention with Didang Decoction (DDD) on the expression of myosin light chain kinase (MLCK), cyclic adenosine monophosphate (cAMP)-1, protein kinase C (PKC), and protein kinase A (PKA) and gene expression in vascular endothelial cells of aortas of diabetic rats, to explore the roles of DDD on the permeability of vascular endothelial cells and its relationship with the MLCK signaling pathway
The finding suggested that the traditional Chinese medicine DDD intervention, early intervention of DDD, significantly ameliorated the injury of vascular endothelium, regulated intercellular junctions of endothelial cells, changed the permeability of vascular endothelial cells, and eventually prevented vascular atherosclerosis

Summary

Introduction

Diabetic macrovascular complications are the leading cause of death and disability causing 70–80% of deaths in diabetic patients [1]. There are many theories about the pathogenesis of diabetic vascular diseases, including insulin resistance, oxidative stress, lipid metabolism disorder, and inflammation theory. According to these theories, many medications have been developed to treat diabetic vascular diseases. We confirmed that early intervention with DDD can significantly increase the serum levels of IL-4 and IL-3 and reduce the expression of TNF-α, MCP-1, CD68, and E-selectin in the aorta, thereby inhibiting the inflammatory injury and delaying the development of diabetic vascular disease in type 2 diabetic rats [3, 4]. This study investigated the effect DDD on the permeability of vascular endothelial cells when used early and discusses its roles in improving endothelial cell damage and its promise in the prevention of diabetic macrovascular complications

Methods

Results

Conclusion