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目的探讨硫化氢(H2S)对脓毒症大鼠动脉压力反射(ABR)的作用及机理。方法盲肠结扎穿刺(CLP)法制作脓毒症大鼠模型,选取47只雄性Spargue-Dawley大鼠随机分为9组:①假手术(SO)+0.9%NaCl(NS)静脉注射组;②SO+硫氢化钠(NaHS)静脉注射组;③CLP+NaHS静脉注射组;④SO+人工脑脊液(aCSF)双侧孤束核(NTS)注射组;⑤SO+NaHS双侧NTS注射组;⑥SO+安慰剂(DMSO)+NaHS组;⑦SO+格列苯脲(Gli)+NaHS组;⑧CLP+安慰剂(DMSO)组;⑨CLP+Gli组。分别在给药前、给药后5 min和30 min 3个时间点对各组大鼠的ABR功能进行测定。结果①同一组内不同时相间ABR值的变化结果:与给药前比较,SO+NaHS静脉注射组、CLP+NaHS静脉注射组、SO+NaHS双侧NTS注射组及SO+安慰剂+NaHS组给药后5 min和30 minABR值均明显降低(P<0.05,P<0.01),而CLP+Gli组明显升高(P<0.05)。②相同时相不同组间ABR值的变化结果:给药前,CLP+NaHS静脉注射组明显低于SO+NS静脉注射组或SO+NaHS静脉注射组(P<0.05);给药后5 min和30 min,CLP+NaHS静脉注射组明显低于SO+NS静脉注射组或SO+NaHS静脉注射组(P<0.05),SO+NaHS静脉注射组明显低于SO+NS静脉注射组(P<0.05);SO+NaHS双侧NTS注射组明显低于SO+aCSF双侧NTS注射组(P<0.01);SO+Gli+NaHS组明显高于SO+安慰剂+NaHS组(P<0.05);CLP+Gli组明显高于CLP+安慰剂组(P<0.05)。结论脓毒症H2S生成增加对ABR功能有降低作用,该作用可能与ATP敏感性钾通道开放有关;脓毒症状态下H2S不仅通过外周静脉系统发挥作用,而且可能通过中枢NTS影响ABR功能。
Objective To investigate the effect and mechanism of hydrogen sulfide (H2S) on arterial pressure reflex (ABR) in septic rats. Methods Septic rat model was made by cecal ligation and puncture (CLP). Forty-seven male Spargue-Dawley rats were randomly divided into 9 groups: ① sham operation (SO) + 0.9% NaCl (NS) NaHS intravenous injection group; ③CLP + NaHS intravenous injection group; ④SO + artificial cerebrospinal fluid (aCSF) bilateral NTS group; ⑤SO + NaHS bilateral NTS injection group; Group; ⑦SO + glibenclamide (Gli) + NaHS group; ⑧CLP + placebo group; ⑨CLP + Gli group. The ABR function of each group was measured before administration, 5 min and 30 min after administration. Results ① The changes of ABR values in different time phases within the same group: SO + NaHS intravenous injection group, CLP + NaHS intravenous injection group, SO + NaHS bilateral NTS injection group and SO + placebo + NaHS group TheABR values at 5 min and 30 min after drug treatment were significantly decreased (P <0.05, P <0.01), while those in CLP + Gli group were significantly increased (P <0.05). (2) Results of ABR changes between different groups in the same time phase: before administration, CLP + NaHS intravenous injection group was significantly lower than SO + NS intravenous injection group or SO + NaHS intravenous injection group (P <0.05); 5 min after administration (P <0.05). Compared with the SO + NS intravenous injection group and SO + NaHS intravenous injection group (P <0.05), SO + NaHS intravenous injection group was significantly lower than SO + NS intravenous injection group (P <0.05); SO + NaHS bilateral NTS injection group was significantly lower than SO + aCSF bilateral NTS injection group (P <0.01); SO + Gli NaHS group was significantly higher than SO + placebo + NaHS group + Gli group was significantly higher than CLP + placebo group (P <0.05). Conclusions Increased production of H2S in sepsis may decrease the function of ABR. This effect may be related to the opening of ATP-sensitive potassium channels. In septic state, H2S not only acts through the peripheral venous system, but also may affect ABR function through central NTS.