截肢创伤致心肌损伤的信号调控机制及其防治

Mechanism of signal regulation and protection of myocardial injury induced by amputation trauma in rats

目的探讨截肢创伤致大鼠心肌组织损伤的发生机制。方法雄性Wistar大鼠42只,体重260～300g,随机分为正常对照组、创伤对照组、硫氢化钠(NaHS,28μmol/kg,截肢后立即腹腔内注射)组、炔丙基甘氨酸(PPG,50mg/kg,截肢后立即腹腔内注射)组、FK506(0.1mg/kg,截肢后立即腹腔内注射)组、螺内酯(20mg/kg,截肢前灌胃,1/d,共6d)组,每组7只。后5组截肢后6h处死。测定各组血浆硫化氢(H2S)、醛固酮浓度,心肌胱硫醚-γ-裂解酶(CSE)活性、醛固酮含量,以及心肌神经钙蛋白(CaN)AβmRNA表达情况并进行组间比较。结果与正常对照组比较,大鼠截肢后6h血浆醛固酮及H2S浓度、心肌醛固酮含量、CaNAβmRNA表达水平均下降(P<0.05)。与创伤对照组比较,予NaHS及FK506干预后,截肢大鼠心肌损伤减轻,血浆醛固酮浓度及心肌CSE活性均升高(P<0.05),而予NaHS、FK506及螺内酯干预后,血浆H2S浓度及心肌醛固酮含量升高、心肌CaNAβmRNA表达水平均下降(P<0.05)。结论醛固酮与其受体结合增加以及血浆H2S、心肌CSE降低是截肢创伤后心肌损伤的重要致病因素。在截肢创伤所致的心肌损伤中,新型气体信号体系——H2S/CSE体系与心肌CaN信号通路存在交互作用。

Objective To explore the generative mechanism of myocardial injury induced by amputation trauma in rats. Methods Forty-two male Wistar rats weighed 260-300g were randomly divided into six groups （7 each）：normal control group, trauma control group, sodium hydrosulfide （NaHS） group, propargyl glycine （PPG） group, tacrolimus （FKS06） group and spironolactone （Spiron） group. Rats in NariS group, PPG group and FK506 group were treated with NariS, PPG and FK506 （28μmol/kg, 50mg/kg and 0. 1mg/ kg, respectively） by intraperitoneal injection immediately after amputation, while in Spiron group were treated with 20mg/kg spironolactone by gavage once a day for 6 days before amputation. Rats in the latter 5 groups were sacrificed 6-hours after amputation. Hydrogen sulphide （H2S） and aldosterone （ALD） levels in plasma, and cystathionine-γ-lyase （CSE） activity, ALD content and calcineurin （CAN） Aβ mRNA expression in myocardial tissue were determined. Results H2S and ALD levels in plasma, CSE activity, AID content and CaN Aβ mRNA expression in myocardial tissue declined significantly in trauma control group than in normal control group （P〈0. 05）. Compared with trauma control group, ALD levels of plasma and CSE activity of myocardial tissue increased remarkably in NaHS and FK506 group （P〈 0. 05）, while H2S level in plasma and ALD content in myocardial tissues increased and CaN Aβ mRNA expression in myocardial tissues decreased significantly in NariS, FK506 and Spiron group （P〈0. 05）. Conclusions The increased binding of ALD and its receptor, and decreased H2S level in plasma and CaN Aβ mRNA expression in myocardial tissue may be the important pathogenic factors in amputation-induced myocardial injuries. The interaction of H2S/CSE system and CaN signaling pathway may play an important role in this pathological process.