Effect of Dendrobii Officinalis Caulis water extract on hyperviscosity rats based on TLR4/NF-κB/ICAM-1 signaling pathway
This study aims to reveal the effect and mechanism of Dendrobii Officinalis Caulis water extract on the rat model of hyperviscosity induced by a high-sugar,high-salt,and high-fat diet.Thirty-six male SD rats were randomized into normal,model,Compound Danshen Tablets(0.5 g·kg-1),and low-,medium-,and high-dose(0.25,0.5,and 1.0 g·kg-1,respectively)Dendrobii Officinalis Caulis water extract groups.Except the normal group,the remaining groups were fed with a high-salt and high-fat diet and received regular gavage of sucrose solution(20 g·kg-1)for 12 consecutive weeks.The modeling was accompanied by gavage of corresponding drugs.During the experimental period,general signs(such as grip strength,automatic activity,vertigo time,and pain threshold),blood rheology,and blood flow in the tail microcirculation were measured.Flow cytometry was employed to detect the positive cells of intercellular cell adhesion molecule 1(ICAM-1/CD54)and vascular cell adhesion molecule 1(VCAM-1/CD106)in the peripheral blood and the Ca2+fluorescence intensity.Enzyme-linked immunosorbent assay was employed to measure the levels of ICAM-1,VCAM-1,platelet endothelial cell adhesion molecule 1(PECAM-1/CD31),endothelin 1(ET-1),thromboxane A2(TXA2),prostaglandin I2(PGI2),nitric oxide(NO),interleukin-1β(IL-1β),C-reactive protein(CRP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and lipopolysaccharide(LPS).Hematoxylin-eosin,Masson,and Gomori's aldehyde-fuchsin staining were used to observe the pathological and morphological changes in rat colon and aorta.Fluorescence quantitative PCR was conducted to determine the mRNA levels of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),nuclear factor-kappaB(NF-κB),ICAM-1,and VCAM-1 in the aortic tissue.Western blot was employed to determine the protein levels of occludin and claudin-1 in the colon tissue and ICAM-1,VCAM-1,and IL-6 in the aortic tissue.Immunohistochemistry and immunofluorescence were employed to detect the expression of TLR4 and NF-κB in the aortic tissue.The results showed that Dendrobii Officinalis Caulis water extract significantly improved the general signs,reduced the whole blood viscosity,whole blood reducing viscosity,and whole blood flow resistance,increased the blood flow of tail microcirculation,reduced the rates of CD54,CD106-positive cells in peripheral blood,and attenuated the blood flow obstruction in the rat model of hyperviscosity.The water extract significantly lowered the serum levels of ICAM-1,VCAM-1,PECAM-1,and ET-1,elevated the PGI2 and NO level,and alleviated vascular endothelial injury.In addition,the water extract decreased the content of IL-1β,TNF-α,IL-6,and CRP in the serum and reduced the vascular inflammatory injury.Moreover,the Dendrobii Officinalis Caulis water extract improved the morphology of colon and aortic tissues,promoted the expression of occludin and claudin-1 in the colon,and down-regulated the mRNA levels of TLR4,MyD88,NF-κB,ICAM-1,and VCAM-1 as well as the protein levels of TLR4,NF-κB,and IL-6 in the aortic tissue.In conclusion,the results suggest that the Dendrobii Officinalis Caulis water extract may regulate the endothelial inflammatory injury via the TLR4/NF-κB/ICAM-1 pathway,thereby ameliorating hyperviscosity.
Dendrobii Officinalis Caulis water extracthyperviscosityintestinal barrierinflammationendothelial injuryadhesion molecule
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