Effects of Zinimaibi Decoction on the expression of LOX-1 in the hindlimb arteries of diabetic rats

Abstract

Objective To investigate the effect and related mechanism of Zinimaibi Decoction on the expression of lectin-like oxidized low-density lipoprotein receptor (LOX)-1 in the hindlimb arteries of diabetic rats. Methods A total of sixty Sprauge-Dawley rats were included in this study. Ten rats were randomly selected as normal control group according to random number table method, whereas all the other rats were fed with high-glucose and high-fat diet combined with the injection of streptozotocin (25 mg/kg) from tail vein to induce diabetes. After successful modeling, all diabetic rats were randomly divided into non-drug intervention group, cilostazol group(10 mg·kg-1·d-1), low dose of Maibi Decoction group(12 g·kg-1·d-1), medium dose of Maibi Decoction group(24 g·kg-1·d-1)and high dose of Maibi Decoction group(48 g·kg-1·d-1)according to random number table method, with 10 rats in each group. After 4 weeks of intervention, body weight, blood glucose, liver function, renal function and total cholesterol(CHO), triglyceride(TG), high density lipoprotein-cholesterol(HDL-C) and low density lipoprotein-cholesterol(LDL-C) were examined.HE staining was used to observe the morphilogical changes of hindlimb artery intima. Western blotting was used to analyze the expression of LOX-1, nuclear factor-κB(NF-κB) p65 and vascular cell adhesion molecule(VCAM)-1 of hindlimb. Results The weight of diabetic rats were decreased and blood glucose were increased significantly compared with non-diabetic rats after modeling (F=4.63, 120.27, all P 0.05). The serum CHO and LDL-C level in the medium and high dose of Maibi Decoction group were downregulated compared with non-drug intervention group, the serum TG level in normal control group, cilostazol group, and all Maibi Decoction groups were decreased significantly compared with non-drug intervention group(F=4.10, 4.97, 17.23, all P<0.01). Mucoid degeneration were found in the hindlimb artery in non-drug intervention group but were improved in all intervention groups, especially in the medium and high dose of Maibi Decoction groups. Compared with non-drug intervention group, the expression of LOX-1 and VCAM-1 protein were decreased significantly in low, medium, high dose of Maibi Decotion intervention group and cilostazol group (F=13.25, 43.01, all P<0.01). The protein level of NF-κB p65 were also decreased significantly in cilostazol group and high dose of Maibi Decoction group compared with non-drug intervention group (F=13.83, P<0.01). Conclusions Zinimaibi Decoction downregulates the expression of LOX-1 in the hindlimb arteries of diabetic rats and inhibits the expression of VCAM-1 by decreasing the expression of NF-κB p65. Key words: Zinimaibi Decoction; Diabetic lower limb atherosclerosis; Lectin-like oxidized low-density lipoprotein receptor-1; Nuclear factor-κB p65; Vascular cell adhesion molecule-1