输血对改善脓毒症急性肾损伤大鼠肾氧合水平和肾功能的作用研究

Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats

目的:探讨输血对脓毒症急性肾损伤大鼠肾脏微血管氧合及肾功能的影响。方法:28只健康雄性12周龄SD大鼠随机分为对照组、脂多糖诱导脓毒症组(LPS组)、脂多糖+液体复苏组(LPS+FR组)、脂多糖+输血组(LPS+BT组),每组各7只。检测各组大鼠肾血流动力学、肾氧合水平和肾功能。实时荧光定量PCR检测肾脏组织中eNOS、iNOS的表达。结果:与对照组相比,LPS输注诱导可引起大鼠血压、肾血流量的早期和持续性下降,输血和液体复苏均明显改善了脓毒症大鼠T2、T3时的血压和T2时的肾血流量(P<0.05);LPS诱导明显降低了大鼠的肾皮质微血管氧张力,液体复苏可明显改善T2时期的肾皮质微血管氧张力,但在T3时间有所下降,而输血可持续改善T2-T3时期的肾皮质微血管氧张力,且在T3时期对大鼠的肾皮质微血管氧张力、左肾静脉压、肾内氧耗的改善作用明显强于液体复苏(P<0.05);T3时期,LPS诱导的脓毒症急性肾损伤大鼠均表现为血清肌酐水平升高和肌酐清除率明显降低(P<0.05),LPS组与LPS+FR组间血清肌酐水平无明显差异(P>0.05),LPS+BT组大鼠血清肌酐水平则较LPS组和LPS+FR组明显降低(P<0.05),但与对照组无明显差异(P>0.05)。LPS+BT组大鼠肌酐清除率明显高于LPS+FR和LPS组,且该三组均明显低于对照组(P<0.05);与对照组相比,LPS诱导脓毒症急性肾损伤大鼠肾脏组织iNOS显著上调,而eNOS表达明显下降(P<0.05)。液体复苏和输血均可恢复大鼠肾脏组织iNOS、eNOS的表达(P<0.05),且输血对大鼠iNOS、eNOS表达的改变优于液体复苏(P<0.05)。结论:脓毒症急性肾损伤大鼠的肾血流量、肾氧合水平和肾功能均显著降低,输血可明显改善脓毒症急性肾损伤大鼠的肾血流量、肾氧合水平和肾功能,可作为一种感染性休克有用的肾脏保护策略。

Objective:To investigate the effects of blood transfusion on renal microvascular oxygenation and renal function in rats with sepsis acute kidney injury.Methods:28 healthy male 12 week old SD rats were randomly divided into control group,lipopolysaccharide induced sepsis group(LPS group),lipopolysaccharide+fluid resuscitation group(LPS+FR group)and lipopolysaccharide+blood transfusion group(LPS+BT group),7 cases in each group.The renal hemodynamics,renal oxygenation and renal function were measured,and the expression of eNOS and iNOS was detected by real-time PCR.Results:Compared with the control group,LPS infusion-induced sepsis could cause early and persistent decrease of blood pressure and renal blood flow in rats.Both blood transfusion and fluid resuscitation significantly improved blood pressure at T2 and T3 and renal blood flow at T2 in sepsis rats(P<0.05).LPS induction significantly reduced the renal cortical microvascular oxygen tension in rats,and fluid resuscitation could significantly improve the renal cortical microvascular oxygen tension in the T2 period,but decreased at T3 time.However,blood transfusion could continuously improve the renal cortical microvascular oxygen tension in the T2-T3 period,and the improvement effect on the renal cortical microvascular oxygen tension,left renal venous pressure,and intrarenal oxygen consumption in the T3 period was significantly stronger than that of fluid resuscitation(P<0.05).At T3,rats with acute renal injury induced by LPS showed increased serum creatinine level and decreased creatinine clearance(P<0.05).There was no significant difference in serum creatinine level between LPS group and LPS+FR group(P>0.05),and the level of serum creatinine in LPS+BT group was significantly lower than that of LPS group and LPS+FR group(P<0.05),but there was no significant difference compared with the control group(P>0.05).The clearance rate of creatinine in the LPS+BT group was significantly higher than that in the LPS+FR and LPS groups,and the three groups were significantly lower than the control group(P<0.05).Compared with the control group,LPS-induced iNOS in the kidney tissue of rats with acute sepsis was significantly up-regulated,while eNOS expression was significantly decreased(P<0.05).Both fluid resuscitation and blood transfusion could restore the expression of iNOS and eNOS in rat kidney tissue(P<0.05),and the change of blood iNOS and eNOS expression was better than fluid resuscitation(P<0.05).Conclusion:The renal blood flow,renal oxygenation level and renal function are significantly reduced in sepsis rats with acute kidney injury,and blood transfusion significantly improve the renal blood flow,renal oxygenation level and renal function in sepsis rats with acute kidney injury,suggesting that blood transfusion may be a useful renal protection strategy for septic shock.