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目的中枢给予硫化氢(H2S)的供体硫氢化钠(NaHS)观察自发性高血压大鼠血压和心率的变化,以明确中枢H2S的心血管效应,并探讨其可能的作用机制。方法雄性WKY大鼠作为SHR大鼠同种系正常对照组;雄性SHR大鼠,随机分为SHR大鼠对照组、NaHS实验组,Apocynin实验组。免疫组织化学方法观察胱硫醚-β-合酶(CBS)在SHR大鼠和WKY大鼠延髓头端腹外侧核区(RVLM)的分布及含量差异。对照组SHR大鼠和NaHS实验组SHR大鼠分别给予侧脑室注射人工脑脊液和不同剂量的NaHS(1,2,4,8nmol/10μl)并观察其血压和心率的变化,Apocynin实验组SHR大鼠侧脑室注射Apocynin后观察其血压和心率的改变情况。酶标法测定四组大鼠RVLM区活性氧(主要为超氧阴离子,O2-)的水平及NADPH氧化酶的活性。结果 CBS在WKY和SHR大鼠RVLM区都有分布,且SHR大鼠RVLM区CBS的含量明显低于WKY大鼠(P<0.05)。与对照组SHR大鼠相比,NaHS实验组SHR大鼠侧脑室注射NaHS(4nmol/10μl)可产生降低血压和减慢心率的心血管效应(P<0.05),侧脑室注射Apocynin(100nmol/10μl)也可降低SHR大鼠的血压和心率(P<0.05)。对照组SHR大鼠RVLM区活性氧的水平和NADPH氧化酶的活性均比WKY大鼠高(P<0.05),NaHS实验组SHR大鼠其RVLM区活性氧的水平较对照组SHR大鼠明显减少且NADPH氧化酶的活性也显著降低(P<0.05),Apocynin实验组SHR大鼠其RVLM区活性氧水平及NADPH氧化酶活性也较对照组SHR大鼠明显降低(P<0.05)。结论 H2S可以抑制SHR大鼠RVLM区NADPH氧化酶的活性,从而减少活性氧的生成,产生降低血压和减慢心率的心血管效应。
Objective To investigate the changes of blood pressure and heart rate in spontaneously hypertensive rats by giving sodium hydrogen sulfite (NaHS), a donor of hydrogen sulfide (H2S), in order to clarify the cardiovascular effects of central H2S and to explore its possible mechanism. Methods Male WKY rats were used as normal control group in SHR rats. Male SHR rats were randomly divided into SHR control group, NaHS experimental group and Apocynin experimental group. The distribution and content of cystathionine-β-synthase (CBS) in the rostral ventrolateral medulla (RVLM) of SHR rats and WKY rats were observed by immunohistochemistry. SHR rats in control group and SHR rats in NaHS experimental group were given intracerebroventricular injection of artificial cerebrospinal fluid and different doses of NaHS (1, 2, 4, 8nmol / 10μl) and observe the changes of blood pressure and heart rate. Apocynin SHR rats The changes of blood pressure and heart rate were observed after intracerebroventricular injection of Apocynin. The level of active oxygen (mainly superoxide anion, O2-) and the activity of NADPH oxidase in RVLM area of four groups were detected by enzyme-linked immunosorbent assay. Results The distribution of CBS in RVLM region of WKY and SHR rats was significantly lower than that in WKY rats (P <0.05). Compared with SHR rats in control group, NaHS (4nmol / 10μl) injected into the lateral ventricle of SHR rats produced cardiovascular effects of lowering blood pressure and heart rate (P <0.05), and intracerebroventricular injection of Apocynin (100nmol / 10μl ) Also decreased blood pressure and heart rate in SHR rats (P <0.05). The levels of reactive oxygen species and activity of NADPH oxidase in RVLM of SHR rats in control group were higher than those in WKY rats (P <0.05). The levels of reactive oxygen species in RVLM of SHR rats in NaHS group were significantly lower than those in SHR rats (P <0.05). The active oxygen level and activity of NADPH oxidase in RVLM area of SHR rats in Apocynin group were significantly lower than those in SHR rats in control group (P <0.05). Conclusion H2S can inhibit the activity of NADPH oxidase in the RVLM of SHR rats, thus reducing the production of reactive oxygen species (ROS) and the cardiovascular effects of lowering blood pressure and heart rate.