肾脏去神经对动脉粥样硬化家兔炎症因子的影响

目的:探讨肾脏去神经(renal denervation,RDN)对动脉粥样硬化(atherosclerosis,AS)家兔肿瘤坏死因子α(TNF-α)、白细胞介素1α(IL-1α)和白细胞介素6(IL-6)的影响。方法:28只雄性新西兰白兔随机分为对照组、RDN后高脂饲养(high-fat diet,HFD)组(RDN组)、假手术后HFD组(假手术组)和单纯HFD组(HFD组),每组7只。测量各组血浆去甲肾上腺素(norepinephrine,NE)、炎症因子及血脂水平;免疫组化检测血管紧张素Ⅱ(Ang Ⅱ)的表达,Western blot检测核因子κB(NF-κB)和血管紧张素Ⅱ 1型受体(AT1R)的表达;real-time PCR检测TNF-α、IL-1α和IL-6 mRNA的表达;光镜下观察肾动脉结构改变和主动脉病理变化。结果:8周后RDN组NE水平明显低于假手术组和HFD组(P0.05);RDN组血浆甘油三酯(TG)水平低于HFD组(P0.05);RDN组的Ang Ⅱ蛋白表达低于假手术组和HFD组(P0.01);RDN组NF-κB蛋白表达低于假手术组(P0.05);RDN组TNF-α和IL-1α的血浆水平低于假手术组和HFD组(P0.05),RDN组IL-6 mRNA的表达低于假手术组(P0.01)。结论:RDN能有效抑制全身交感神经活性,降低血浆TG水平,减轻血管炎症反应,延缓动脉粥样硬化的发展。

Effects of renal denervation on inflammatory factors in a rabbit model of early atherosclerosis

AIM: To evaluate the effects of renal denervation (RDN) 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 were divided into control group, RDN+ high-fat diet (HFD) group (RDN group), sham+HFD group (sham group) and HFD group. The rabbits in later 3 groups were fed with 2% cholesterol for 8 weeks to establish an early atherosclerosis model. The blood samples were collected to test the levels of lipids, norepinephrine (NE), TNF-α, IL-1α and IL-6. The protein expression of angiotensin Ⅱ (Ang Ⅱ) was detected by the method of immunohistochemistry. The levels of nuclear factor-κB (NF-κB) and Ang II 1 type receptor (AT1R) were evaluated by Western blot. The mRNA expression of TNF-α, IL-1α and IL-6 was determined by real-time PCR. RESULTS: After 1 d of RDN procedure, the NE level was lower in RDN group than that in sham group (P<0.01). After 8 weeks, the NE level was lower in RDN group than that in sham group and HFD group (P<0.05), and triglyceride (TG) was lower in RDN group than that in HFD group (P<0.05). The protein expression of Ang II was decreased in RDN group compared with sham group and HFD group (P<0.01). The protein expression of NF-κB was lower in RDN group than that in sham group (P<0.05). The plasma levels of TNF-α and IL-1α were reduced in RDN group compared with sham group and HFD group (P<0.05). The mRNA expression of TNF-α, IL-1α and IL-6 was reduced in RDN group compared with sham group (P<0.05). CONCLUSION: RDN inhibits sympathetic activity, decreases the plasma level of TG, and alleviates inflammatory reactions in the rabbits with atherosclerosis.