诱导性低温复苏失血性休克大鼠肾组织过氧化物酶体增殖物激活受体γ辅助激活因子、法尼酯衍生物X受体表达研究

Effect of induced hypothermia resuscitation on the expression of peroxisome proliferator activated receptor gamma coactivator-1 and farnesoid X receptor in kidney of rats with hemorrhagic shock

目的探讨诱导性低温复苏对失血性休克大鼠肾组织中过氧化物酶体增殖物激活受体γ辅助激活因子(PGC-1)、法尼酯衍生物X受体(FXR)表达的影响。方法选取40只成年SD大鼠,随机分为对照组(n=8)、常温复苏组(n=16)及低温复苏组(n=16)。常温复苏组、低温复苏组大鼠建立失血性休克模型,并于维持休克状态60 min后,分别以常温(38℃)、低温(32℃)复苏。对照组仅进行相关手术操作,不建立休克模型。采用蛋白质印迹法和聚合酶链式反应检测复苏3 h后大鼠肾组织中PGC-1、FXR蛋白及mRNA表达情况。结果建模前,3组大鼠心率、平均动脉压比较,差异无统计学意义(P>0.05)。建模后,常温复苏组、低温复苏组大鼠心率均较建模前明显升高,平均动脉压均较建模前明显降低,差异有统计学意义(P<0.05)。复苏后,常温复苏组、低温复苏组大鼠心率均较建模后降低,平均动脉压均较建模后升高,差异有统计学意义(P<0.05)。复苏结束后3 h,常温复苏组大鼠肾组织中PGC-1 mRNA表达量高于对照组,而低温复苏组大鼠肾组织中PGC-1 mRNA表达量低于对照组、常温复苏组,差异均有统计学意义(P<0.01)。复苏结束后3 h,常温复苏组、低温复苏组大鼠肾组织中FXR mRNA表达量均低于对照组,且低温复苏组低于常温复苏组,差异均有统计学意义(P<0.01)。复苏结束后3 h,常温复苏组、低温复苏组大鼠肾组织PGC-1、FXR蛋白表达均低于对照组,且低温复苏组低于常温复苏组,差异有统计学意义(P<0.05)。常温复苏组、低温复苏组大鼠在休克模型期、复苏期均无死亡。Kaplan-Meier生存分析结果显示,低温复苏组大鼠72 h存活率显著高于常温复苏组,差异有统计学意义(P<0.05)。结论诱导性低温可调节失血性休克大鼠模型肾组织中PGC-1和FXR基因表达,从而改善能量代谢失衡。

Objective To investigate the effects of induced hypothermia resuscitation on the expression of peroxisome proliferator activated receptor gamma coactivator-1(PGC-1)and farnesoid X receptor(FXR)in kidney of rats with hemorrhagic shock.Methods A total of 40 adult SD rats were randomly divided into control group(n=8),normal-temperature resuscitation group(n=16)and low-temperature resuscitation group(n=16).The rats in normal-temperature resuscitation group and low-temperature resuscitation group established hemorrhagic shock model,and after 60 min of shock,the rats were respectively resuscitated at normal temperature(38℃)and low temperature(32℃).The control group were performed the relevant surgical operations only,without establishing hemorrhagic shock model.Western blot and polymerase chain reaction were used to detect the changes of PGC-1 and FXR protein and mRNA expression in kidney of rats after 3 hours of resuscitation.Results Before establishing the hemorrhagic shock model,there were no significant differences in heart rate and mean arterial pressure among the three groups(P>0.05).After establishing the hemorrhagic shock model,the heart rate of rats in normal-temperature resuscitation group and low-temperature resuscitation group significantly increased,while the mean arterial pressure decreased significantly(P<0.05).After the resuscitation,the heart rate of rats in normal-temperature resuscitation group and low-temperature resuscitation group decreased and the mean arterial pressures increased than establishing the hemorrhagic shock model,with statistical significance(P<0.05).Three hours after the resuscitation,the expression level of PGC-1 mRNA in kidney tissues of rats in the normal-temperature resuscitation group was higher than that in the control group,while the expression level of PGC-1 mRNA in kidney tissues of rats in the low-temperature resuscitation group was lower than that in the other two groups with statistical significance(P<0.01).Three hours after the resuscitation,the expression level of FXR mRNA in kidney tissue of rats in the normal-temperature resuscitation group and low-temperature resuscitation group was lower than that in the control group,and the expression level of FXR mRNA in the low-temperature resuscitation group was lower than that in normal-temperature resuscitation group,the differences were statistically significant(P<0.01).Three hours after the resuscitation,the protein expression levels of PGC-1、FXR in kidney tissue of rats in the normal-temperature resuscitation group and low-temperature resuscitation group were significantly lower than those in the control group,and those expression levels in the low-temperature resuscitation group were significantly lower than those in the normal-temperature resuscitation group(P<0.05).There was no death in normal-temperature resuscitation group and low-temperature resuscitation group during shock model period and resuscitation period.Kaplan-meier survival analysis showed that the 72-hour survival rate of rats in low-temperature resuscitation group was significantly higher than that in the normal-temperature resuscitation group(P<0.05).Conclusion Induced hypothermia resuscitation can regulate the expression of PGC-1 and FXR genes in the kidney tissue of the hemorrhagic shock model rats,thereby improving the energy metabolism imbalance.