他罗利姆对截肢大鼠NO和H_2S的活化作用

目的观察大鼠截肢创伤应激后重要血管舒缩因子的变化及他罗利姆（FK506）对其调控作用,为截肢术后引起的远隔器官损伤的干预治疗提供依据。方法建立大鼠左后肢截肢创伤模型,将雄性Wistar大鼠80只随机分为10组：正常对照组、截肢后1h、2h、4h、6h、12h、24h、48h、72h组、他罗利姆干预组。测定血浆H2S、AngⅡ、NO的含量,心、肺、肝、肾组织CSE活性。结果与对照组比较,截肢创伤后1h血浆AngⅡ含量明显升高,于6h达峰值（684.497±77.515）pmol/L（P〈0.05）,72h恢复至正常水平;血浆NO、H2S截肢创伤后4h明显降低,6h达最低,分别为（8.553±0.896）μmol/L（P〈0.05）、（55.654±6.332）μmol/L（P〈0.05）,24h恢复正常值。他罗利姆干预后,血浆H2S、NO,心、肺、肝、肾组织CSE活性较创伤6h组明显升高（P〈0.05）,血浆AngⅡ含量无明显变化。结论大鼠截肢创伤应激后血管收缩作用增强,他罗利姆主要升高血管舒张因子NO和H2S,对AngⅡ无明显调控作用。

Activation effect of tacrolims on hydrogen sulfide and nitric oxide in rats after amputation

Objective To observe the changes of major vasoconstriction and vasodilation factors in rats after amputation and the role of FK506 in their regulation for the intervention treatment of distal organ injuries induced by amputation.Methods Eighty male Wistar rats were randomly divided into control group,1,2,4,6,12,24,48,72h post-amputation groups,and tacrolims group（n=8）.Plasma levels of hydrogen sulfide（H2S）,angiotensinⅡ（AngⅡ） and nitric oxide（NO） were measured,and cystathionineγ-lyase（CSE） activity in heart,lung,liver and kidney tissues was detected.Results Compared with control group,the plasma AngⅡlevel was significantly increased 1h after amputation,reached its peak 6h after amputation（684.497±77.515）pmol/L（P0.05）,and returned to normal 72h after amputation,while the plasma NO and H2S levels were significantly decreased 4h after amputation,reached their lowest value 6h after amputation（8.553±0.896）μmol/L and（55.654±6.332）μmol/L（P0.05）,and returned to normal 24h after amputation.The plasma NO and H2S level and the CSE activity were significantly increased in different tissues 6h after intervention with tacrolims（P0.05）,with no obvious change in plasma AngⅡlevel.Conclusion Vasoconstriction increases in rats after amputation,tacrolims increases plama H2S and NO level but has no significant effect on Ang Ⅱ.