脑内肿瘤坏死因子-α参与高血压发病机制的研究

The study on TNF-α playing role in pathogenesis of hypertension by modulating norepinephrine

目的探讨脑内肿瘤坏死因子(TNF)-α通过调节下丘脑室旁核去甲肾上腺素影响高血压大鼠交感神经活动的机制。方法雄性成年SD大鼠,将血管紧张素Ⅱ(ANGⅡ)溶解在生理盐水中由静脉内以10ng.kg-1.min-1持续给药4周制作高血压模型,对照组大鼠给予生理盐水,治疗组通过侧脑室给予TNF-α阻断剂己酮可可碱(PTX)4周,非治疗组给予人工脑脊液(aCSF)4周。大鼠分为高血压治疗组(ANGⅡ+PTX)、高血压非治疗组(ANGⅡ+aCSF)、对照治疗组(生理盐水+PTX)和对照非治疗组(生理盐水+aCSF)。4周后采用高效液相色谱法(HPLC)测量下丘脑室旁核和血浆中去甲肾上腺素水平。结果高血压大鼠下丘脑室旁核和血浆中去甲肾上腺素水平升高(P<0.05),经侧脑室给予PTX4周后可降低下丘脑室旁核和血浆中去甲肾上腺素水平(P<0.05)。结论脑内TNF-α可通过调节下丘脑室旁核去甲肾上腺素水平参与高血压的发病机制,阻断中枢TNF-α合成可在一定程度上降低交感神经兴奋性。

Objective Angiotensin Ⅱ（ANGⅡ）-induced inflammatory responses have been reported to contribute to the pathogenesis of hypertension.This study is to explore the possible roles of brain TNF-α in sympathetic activities of hypertensive rats through modulation of norepinephrine in paraventricular nucleus（PVN）.Methods Adult male SD rats were used to establish hypertensive model by continuous intravenous infusion with ANGⅡ in saline at 10 ng·kg-1·min-1 for 4 weeks.Rats in the control group were administered with normal saline（NS）.Continuous intracerebroventricular（ICV） infusion of TNF-α blocker pentoxifylline（PTX） and artificial cerebrospinal fluid（aCSF） were given respectively to the treatment group and non-treatment group for 4 weeks.The rats were divided into hypertension treatment group（ANGⅡ＋PTX）,hypertension non-treatment group（ANGⅡ＋aCSF）,treatment control group（NS＋PTX） and non-treatment control group（NS＋aCSF）.High performance liquid chromatogram（HPLC） was used to test the level of norepinephrine in PVN and in plasma 4 weeks later.Results Hypertensive rats showed elevated levels of norepinephrine in PVN and in serum（P0.05）,which were ameliorated by 4-week ICV of TNF-α blocker PTX.Conclusion Norepinephrine in plasma can be an indirect signal of sympathetic excitation.TNF-α may be involved in hypertension by modulating norepinephrine in the PVN,and may also reduce sympathetic excitation by blocking TNF-α synthesis in a certain degree.