Effect of NF-κB inhibitor on Toll-like receptor 4 expression in left ventricular myocardium in two-kidney-one-clip hypertensive rats

摘要

OBJECTIVE: To investigate the effects of an inhibitor of NF-κB, PDTC (pyrrolidine dithiocarbamate), on TLR4 (Toll-like receptor 4) expression in the left ventricle of Goldblatt hypertension rats. MATERIALS AND AND METHODS: Goldblatt rat model of two-kidney, one-clip (2K1C) hypertension was established in 70 healthy male rats. The rats were randomly divided into sham operation group (S group, n=20), non-drug intervention hypertension group (H group, n=25), and PDTC intervention group (P group, n=25). P group was injected with PDTC. The clip was inserted in the left renal artery of H group and P group (2K1C). Eight weeks after the operation, the rats were sacrificed and the samples of the left ventricle were collected. The concentration of AngII in the left ventricle was assessed by radioimmunoassay. RT-PCR was used to examine the mRNA expression of TLR4 in the left ventricle. Immunohistochemistry was adopted to examine the location of TLR4 and NF-κB in the myocardium. Victoria blue-Ponceau staining of Cardiac collagen was used to evaluate the degree of myocardial fibrosis. RESULTS: Eight weeks after the operation, caudal SBP, meridional end-systolic stress, left ventricular mass index, relative wall thickness, cardiac fibrosis degree, and the concentration of AngII in the left ventricle in P group were significantly lower than those in H group (p<0.01). In cardiac myocytes of S group and P group, TLR4 expression was diffused and presumably cytoplasmic. TLR4 mRNA expression in P group was significantly lower than that of H group (p<0.01). CONCLUSIONS: PDTC not only inhibited the activation of NF-κB, but decreased TLR4 expression and AngII content, indicating that the inflammatory signals and oxidative stress mediated by TLR4/NF-κB are involved in the occurrence and development of left ventricular remodeling. Intervention with TLR4/NF-κB and anti-inflammatory and anti-oxidative therapy may be a new target to reverse left ventricular remodeling.