FBXW7 and RhoA / Rho kinase protein expressions are involved in myocardial fibrosis in diabetic rats / 中国药理学与毒理学杂志

ABSTRACT

Objective To investigate the relationship between the expression of F-box / Protein-containing WD-40 domain protein (FBXW7), Ras homologous family member A (RhoA), Rho-associated coiled coil protein kinase (ROCK) and myocardial fibrosis in diabetes. Methods SD The rats were randomly divided into a normal control group and a diabetes model group, and a disposable ip streptozotocin 60 mg · kg-1 was used to establish a rat model of type 1 diabetes, which was tested at 2, 4, 8, 12, and 16 weeks, respectively. HE staining to observe the morphological changes of rat heart tissue; Masson staining and measurement of myocardial hydroxyproline (HYP) content to observe the degree of myocardial collagen deposition; ELISA to detect serum FBXW7, transforming growth factor β1 (TGF-β1) and connective tissue growth Factor (CTGF) content; Western blotting and immunohistochemical detection of FBXW7, RhoA and ROCK1 protein expression in myocardium. Results The myocardial cells of the diabetic model group were found to have varying degrees of focal myocardial cell degeneration, necrosis, and fibrous tissue. Hyperplasia, etc. Compared with the normal control group, the collagen deposition area and collagen content in the myocardial tissue of the model group rats increased significantly at 4 to 16 weeks (P <0.05, P <0.01), showing an increasing trend; 2 to 4 weeks The content of FBXW7 in the serum of rats increased significantly (P <0.01). It decreased at 8 weeks, but was still significantly higher than the normal control group (P <0.01); at 8 to 16 weeks, the levels of TGF-β1 and CTGF in the serum of rats gradually increased (P <0.01). The results showed that the myocardial RhoA and ROCK1 protein expressions in the model group were significantly higher than those in the normal control group at each time point (P <0.05, P <0.01); the myocardial FBXW7 expression in the model group rats was higher than that in the normal control group at 2 to 12 weeks Significantly increased (P <0.01, P <0.01), with the highest expression at 4 weeks, decreased expression at 8-16 weeks, and negatively correlated with time (r = -0.988, P <0.05), but still higher than the normal control group ( P <0.01). Conclusion FBXW7 and RhoA / Rho kinase are involved in the development of myocardial fibrosis in diabetic rats and may become targets for the treatment of diabetic cardiomyopathy.