Effects Of Renal Denervation On Inflammatary Factors In A Rabbit Model Of Early Atherosclerosis

Background:Atherosclerosis is a common cardiovascular disease. It causes of highly cardiovascular morbidity and mortality. Some experts consider that atherosclerosis is a chronic inflammation disease. High lipid level increases the expression of lipoproteins (oxidized low-density lipoprotein and cholesterol) in arterial walls. Ox-LDL could damage arterial intima, which results in endothelial dysfunction, lipid deposition and vascular inflammation. Therefore, inflammation plays an important role in the development of atherosclerosis. Recent studies have found that Ang Ⅱ can regulate the expression of NF-κB protein, aggravate inflammation and affect the proliferation and migration of smooth muscle cells. It finally leads to the vascular remodeling and apoptosis. Recent study shows that renal sympathetic nerve regulates the activity of renin-angiotensin system (RAS), and renal sympathetic afferent or efferent nerves could be blocked selectively by catheter ablation. It makes a great progress on reducing sympathetic overload for patients with resistant hypertension and heart failure. But its effect on atherosclerosis has not been clear.Objective:To evaluate the effects of renal denervation on the expression of tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and interleukin-6 (IL-6) in a rabbit model of early atherosclerosis. Methods: New Zealand male rabbits (n=28) were divided into control group, renal denervation (RDN) group, sham group, high-fat-diet (HFD) group. The rabbits in later 3 groups were fed with 2% cholesterol for 8 weeks to establish early atherosclerosis model. The blood samples were collected to test lipids, norepinephrine (NE), TNF-α, IL-1α and IL-6 levels. The protein level of AngⅡ was detected by immunohistochemistry. The levels of NF-κB and Ang Ⅲ type receptor (AT1R) were evaluated by Western boltting. The mRNA expression of TNF-α, IL-1α and IL-6 were determined by RT-PCR. Results:The NE level was lower in RDN group than that in sham group, after 1 d of RDN procedure (P<0.01 for both). At the end of 8 weeks, the NE level was lower in RDN group than that in sham group and HFD group (P<0.05 and P<0.01, respectively). TG was lower in RDN group than that in HFD group (P<0.05). The protein level of Ang Ⅱ was decreased in RDN group compared with sham group and HFD group (P<0.01 for both). The protein level of NF-κB was lower in RDN group than that in sham group (P <0.05). The plasma level of TNF-α and IL-1α were reduced respectively in RDN group compared with sham group and HFD group (P<0.05 and P<0.01). The mRNA expression of TNF-α, IL-1α and IL-6 was reduced respectively in RDN group compared with sham group (P<0.05, P<0.05 and P<0.01). Conclusions:RDN could inhibit sympathetic activity, decrease the levels of TG, and alleviates inflammation in the rabbit with atherosclerosis.