国产多极消融导管对醋酸脱氧皮质酮诱导高血压模型猪下丘脑炎症反应及交感活性的抑制作用

Inhibition of hypothalamus inflammatory and sympathetic system reaction in DOCA induced hypertension model by renal denervation with a multi-electrode ablation system

目的探讨国产多极消融导管对醋酸脱氧皮质酮(DOCA)诱导高血压模型猪下丘脑炎症反应及交感活性的抑制作用.方法研究入选12头3月龄的实验动物猪分为三组,分别为DOCA诱导的高血压模型+RDN消融组、DOCA诱导的高血压模型+假手术组和正常对照组,每组4头.DOCA诱导的高血压模型消融组采用自主研发的国产Spark多极消融导管对其进行肾动脉去神经消融术.术后1个月随访三组实验动物的平均动脉压(MAP),通过Elisa方法和荧光免疫组化方法分析下丘脑炎性因子、交感兴奋相关蛋白的表达水平.结果DOCA高血压模型消融组术后MAP显著降低[(141.25±2.60)mm Hg比(120.38±2.46)mm Hg,P<0.001];DOCA诱导高血压模型消融组与DOCA诱导高血压模型假手术组比较,下丘脑白介素-6(IL-6)水平[(9.60±1.81)ng/ml比(4.52±0.32)ng/ml,P=0.009]及肿瘤坏死因子-α(TNF-α)水平[(10.92±0.51)pg/ml比(1.37±1.02)pg/ml,P<0.001]显著降低;下丘脑c-Fos蛋白表达比例[(8.03±0.69)%比(15.75±1.47)%,P=0.011]及Fos-B蛋白的表达比例[(16.70±0.49)%比(37.52±0.70)%,P<0.001)]与假手术组比较,RDN消融组均显著降低.结论国产Spark多极消融导管进行肾动脉去神经消融术后能够有效降低DOCA诱导的高血压模型猪的平均动脉压.同时对于该模型的中枢下丘脑炎症反应及交感神经兴奋性均具有抑制作用.

Objective To investigate the inhibition of hypothalamus inflammatory and sympathetic system reaction in deoxycortone acetate(DOCA)induced hypertension model by renal denervation(RDN)with a multielectrode ablation system.Methods 12 Bama pigs were randomly assigned to 3 groups:Control group(n=4),DOCA induced hypertension+Sham group(n.=4)and DOCA induced hypertension+RDN group(n.=4).1 month after the operation,the mean blood pressure,expression of inflammatory factors and sympathetic system related proteins in hypothalamus were tested by Elisa and fluorescence immunity.Results MAP in DOCA induced hypertension+RDN group was significantly reduced[(141.25±2.60)mm Hg vs.(120.38±2.46)mm Hg,P<0.001].Meanwhile inflammatory factors as IL-6[(9.60±1.81)ng/ml vs.(4.52±0.32)ng/ml,P=0.009]and TNF-a[(10.92±0.51)pg/ml vs.(1.37±1.02)pg/ml,P<0.001]were also attenuated in DOCA induced hypertension+RDN group.The sympathetic system related proteins in hypothalamus as c-Fos[(8.03±0.69)%vs.(15.75±1.47)%,P=0.011]and Fos-B[(16.70±0.49)%vs.(37.52±0.70)%,P<0.001)]showed lower expression in DOCA induced hypertension+RDN group.Conclusion RDN proceeded by multi-electrode ablation catheter could attenuate MAP of DOCA induced hypertension.Inhibition of the inflammatory reaction and over reaction of sympathetic system could be the possible mechanism of this procedure.