硫化氢对脓毒症大鼠动脉压力反射的影响

Effect of Hydrogen Sulfide on Arterial Baroreflex in Rat with Sepsis

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 potential role and mechanism of hydrogen sulfide （H2S） in regula- ting arterial baroreflex （ABR） in septic rats. Methods The rat model of cecal ligation and puncture （CLP） induced sepsis was established. Forty-seven male Spargue-Dawley rats were randomly divided into 9 groups：①Sham opera- tion （SO）＋0.9% NaCI（NS） intravenous injection （i. v. ） group;② SO＋NaHS i. v. group; ③ CLP＋NaHS i. v. group;④SO＋artificial cerebrospinal fluid （aCSF） bilater nucleus tractus solitarii （NTS） microinjection group;⑤ SO＋ NaHS bilater NTS mieroinjection group;⑥SO＋vehicle （DMS（））＋NaHS group;⑦SO ＋ Gli ＋ NaHS group;⑧CLP＋vehicle （DMS（）） group;⑨CLP＋GIi group. The ABR function was measured before administra tion and 5 min and 30 min after administration. Results ①The ABR value of rats at different time in the same group： Compared with the ABR value before administration in the SO＋ NaHs i.v. group, CLP＋NaHS i. v. group, SO＋NaHS bilater NTS microinjection group, and SO＋vehicle＋NaHS group, the ABR values of rats sig nificantly decreased at 5 min and 30 min after administration （P〈0.05, P〈0.01）, which significantly increased in the CLP＋GIi group at 5 min and 30 min after administration （P〈0.05）.②The ABR value of rats at the same time in the different groups： Before administration, the ABR value of rat in the CLP＋ Naris i. v. group was significantly lower than that in the SO＋NS i. v. group or SO＋NaHS i. v. group （P〈0.05）. At 5 min and 30 min after adminis-tration, the ABR value of rat in the CLP＋NaHS i. v. group was significantly lower than that in the SO＋NS i. v. group or SO＋NaHS i. v. group （P〈0.05）, which in the SO＋NaHS i. v. group or SO＋NaHS bilater NTS micro- injection group was significantly lower than that in the SO＋NS i. v. group or SO＋aCSF bilater NTS microinjection group, respectively （P〈0.05, P〈0.01 ）, in the SO＋ Gli＋NaHS group or CLPq-Gli group was significantly higher than that in the SO＋vehicle^-NaHS group or CLP＋vehicle group, respectively （P〈0. 05）. Conclusions H2S plays an adverse role in septic ABR function, and opening KATP channel located at the pathway of ABR, may be the mechanism involved in the down-regulation of ABR function in septic rat. Notably, the NTS may be also responsible for reduction of ABR value.