H_2S供体——NaHS对肢体缺血再灌注远隔脏器损伤的保护性作用

Protective effect of NaHS,the supplier of H_2S,on the injury of remote organs following hind limb ischemia/reperfusion

目的观察双下肢肢体缺血再灌注(IR)所致心脏、肝脏和肾脏的损伤及H2S对这种损伤的保护作用,为肢体IR引起的远隔器官损伤的干预治疗提供理论依据。方法采用双下肢IR大鼠模型,Wistar大鼠28只随机分为对照组、缺血4h组、缺血4h再灌注4h组、缺血再灌后NaHS干预(IR+NaHS)组(其中NaHS作为H2S的供体可在大鼠体内生成H2S)。干预结束后,心、肝、肾组织HE染色观察病理变化,测定血浆H2S浓度、血浆中心肌酶学指标(CK、CK-MB和Tn-T)以及肝肾功能指标(ALT、AST和Cr、Ur)。结果与对照组相比,缺血4h组血浆CK、CK-MB及Tn-T浓度升高,缺血再灌注组较缺血组进一步升高;缺血组与对照组比较,血浆ALT、AST和Cr、Ur含量无显著变化,缺血再灌注组较缺血组显著升高;IR+NaHS组上述指标较缺血再灌注组均显著降低。病理检查可见缺血后心、肝、肾组织轻度病理改变,缺血再灌组组织损伤更加明显,IR+NaHS组相对减轻。结论肢体缺血再灌注可以引起心、肝、肾的损伤,H2S干预可以对这种损伤起到一定的保护作用。

Objective To observe the injury to the heart, liver and kidney induced by hind limb ischemia/reperfusion （I/R）, and to study the protective effect of H2S by attenuating this injury, in order to offer a theoretical basis for therapeutic application. Methods A model of hind limb I/R was reproduced. 28 rats were divided randomly into 4 groups： normal control group （C, n=8）, ischemia 4h group （I, n=8）, ischemia 4h and reperfusion 4h group （I/R, n=6） and I/R＋NaHS group （n=6） （NariS can provide H2S for rats in vivo）. The concentrations of CK, CK-MB, Tn-T, ALT, AST, Cr and urea in blood plasma were determined. The pathological changes in the heart, liver and kidney were observed with HE staining. Results The concentration of CK, CK-MB and Tn-T in I group increased significantly compared with that in C group, and that in I/R group was higher than in I group. No significant difference was found in plasma concentration of ALT, AST, Cr and Ur between C group and I group, while it they were increased significantly in I/R group compared with that in I group, and that in I/R＋NaHS group were decreased significantly compared with that in I/R group. Pathological examination revealed pathological findings of injury to the heart, liver and kidney in I group, and even more serious injuries were found in I/R group than in I group, while the they were less marked in IR＋NaHS group compared with that in I/R group. Conclusion Hind limb ischemia/reperfusion may result in injury to the heart, liver and kidney. H2S may attenuate injury to remote organs follawing hind limb ischernia/reperfusion.