高容量血液滤过对感染性休克所致急性肾损伤影响的实验研究

Experimental study on the effect of high volume hemofiltration to septic shock induced acute kidney injury

目的 研究高容量血液滤过（High Volume Hemofiltration,HVHF）对感染性休克所致急性肾损伤（Acute Kidney Injury,AKI）的影响,并探讨其可能机制.方法 18只猪随机分为对照组、连续性肾脏替代治疗（continuous renal replacement therapy,CRRT）组和HVHF组,静脉注射大肠杆菌脂多糖（lipopolysaccharide,LPS）诱导感染性休克模型.各组给予液体复苏及血管活性药物维持保证组织灌注,复苏成功后根据分组给予不同处理：对照组不予特殊处理,CRRT组和HVHF组分别行超滤率为25ml/（kg·h）和85ml/（kg·h）的血液滤过治疗.记录各组血流动力学指标、血管活性药物用量及维持时间,检测血浆中IL-6和IL-10浓度、肾组织NF-κB表达水平,并观察肾组织病理改变.结果 各组在给入LPS后约40-60min成功复制出休克模型;各组血流动力学指标在30min、40min、50min及60min时间点与基础相比差异均有统计学意义（P＜0.05）;HVHF组CO值在T6时下降较少,高于基础正常值,与其它两组相比具有统计学差异（P＜0.05）;HVHF组的dPmax在T4、T5、T6时较其它两组有明显升高（P＜0.05）;HVHF组的补液量较其它两组明显减少（P＜0.01）,CRRT组较对照组减少（P＜0.05）;在T4、T5、T6时间点HVHF组去甲肾上腺素用量较前下降,与其它两组相比有明显统计学差异（P＜0.01）;与CRRT组相比,HVHF组IL-6在T3-T6下降明显,IL-10在T2-T6下降明显,差异均有统计学意义（P＜0.05）;HVHF组肾NF-κB的mRNA相对表达量明显低于其它两组（P＜0.01）,CRRT组低于对照组（P＜0.05）;与对照组及CRRT组相比,HVHF组肾脏病理评分明显降低（P＜0.01）.结论 HVHF能够减少血管活性药物的用量和液体复苏量,有效降低血浆IL-6、IL-10浓度及肾组织NF-κB的表达水平,改善肾组织病理改变,对感染性AKI具有一定的肾保护作用.

Objective To investigate the effect and mechanisms of high volume hemofiltration （HVHF） to septic shock induced acute kidney injury （AKI）. Methods Eighteen pigs were randomly divided into control group, continuous renal replacement therapy （CRRT） group or HVHF group, and then intravenously infused with Escherichia coli lipopolysaccharide （LPS） to induce septic shock. Animals were given fluid resuscitation and vasoactive drugs to maintain tissue perfusion. After successful resuscitation, animals in the control group were managed without specific measures, and those in the other two groups were treated with continu- ous venovenous hemofiltration （CVVH, ultrafiltration rate 25 ml/kg/h） or HVHF （ultrafiltration rate 85 ml/kg/ h）. DATA about hemodynamic parameters, vasoactive drug dosage and therapeutic duration, plasma IL-6 and IL-10, NF-kB expression in kidney tissue, and kidney pathological changes were collected. Results Animal shock model was established after LPS administration for 40-60 min. Hemodynamic parameters were statis- tically different at 30 min, 40 min, 50 min and 60 min time points compared with the baseline status in each of the three groups （P〈0.05）. The dPmax at T4, T5 and T6 time points were significantly higher in HVHF group than in the other two groups （P〈0.05）. Fluid resuscitation volume was significantly lower in HVHF group than in the other two groups （P〈0.01）, and was significantly lower in CRRT group than in control group （P〈0.05）. Norepinephrine dosage decreased more at T4, T5, T6 time points than at baseline （P〉0.05） in HVHF group, and the difference was statistically significant as compared with that in the other two groups （P〈0.01）. Plasma IL-6 decreased more at T3-T6 time points and plasma IL-10 decreased more at T2-T6 time points in HVHF group than in CRRT group （P〈0.05）. NF-kB mRNA in kidney was lower in HVHF group than in the other two groups （P〈0.01）, and was lower in CRRT group than in the control group （P〈0.05）. Kidney pathology score was lower in HVHF than in the other two groups （P〈0.01）. Conclusion HVHF led to the decreases of vasoactive drug dosage, fluid volume for resuscitation, NF-kB expression in kidney, inflammatory cytokine expression, and kidney pathological changes, thus protected the kidney from AKI during septic shock.