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中华损伤与修复杂志(电子版)

中华损伤与修复杂志(电子版) ›› 2015, Vol. 10 ›› Issue (05) : 388 -394. doi: 10.3877/cma.j.issn.1673-9450.2015.05.004

所属专题： 文献；

论著

丙酮酸钠羟乙基淀粉对50%总体表面积Ⅲ度烧伤大鼠肾血流量和肾功能的影响
高明娟1, 刘维维2, 王晓娜2, 刘洋2, 白晓东2, 周方强3, 刘锐4, 郑金光2, 赵增凯5, 胡森5,†()   
  1. 1. 100048　北京，解放军总医院第一附属医院全军创伤修复与组织再生重点实验室暨皮肤损伤修复与组织再生北京市重点实验室；100039　北京，武警总医院烧伤整形科
    2. 100039　北京，武警总医院烧伤整形科
    3. 60008　美国芝加哥费森尤斯透析中心；201203　上海三代医药科技有限公司
    4. 150040　哈尔滨市第五医院烧伤科
    5. 100048　北京，解放军总医院第一附属医院全军创伤修复与组织再生重点实验室暨皮肤损伤修复与组织再生北京市重点实验室
  • 收稿日期:2015-03-26 出版日期:2015-10-01
  • 通信作者: 胡森
  • 基金资助:
    军队十一五医学科研专项课题基金资助项目(06Z055)

Effects of sodium pyruvate-hydroxyethyl starch on renal blood flow and kidney function in rats with 50% total body surface area full thickness scald injury

Mingjuan Gao1, Weiwei Liu2, Xiaona Wang2, Yang Liu2, Xiaodong Bai2, Fangqiang Zhou3, Rui Liu4, Jinguang Zhen2, Zengkai Zhao5, Sen Hu5,†()   

  1. 1. Key Research Laboratory of Tissue Repair and Regeneration of People′s Liberation Army, and Beijing Key Research Laboratory of Skin Injury and Repair Regeneration, the First Affiliated to General Hospital of People′s Liberation Army, Beijing 100048, China; Department of Burn and Plastic Surgery, the General Hospital of Chinese People′s Armed Police Forces, Beijing 100039, China
    2. Department of Burn and Plastic Surgery, the General Hospital of Chinese People′s Armed Police Forces, Beijing 100039, China
    3. Chicago Fresenius Hemodialysis Center, Chicago 60008, America; Shanghai three generation of medical science and technology company, Shanghai 201203, China
    4. Department of Burn Surgery, the Fifth Hospital of Harbin, Harbin 150040, China
    5. Key Research Laboratory of Tissue Repair and Regeneration of People′s Liberation Army, and Beijing Key Research Laboratory of Skin Injury and Repair Regeneration, the First Affiliated to General Hospital of People′s Liberation Army, Beijing 100048, China
  • Received:2015-03-26 Published:2015-10-01
  • Corresponding author: Sen Hu
  • About author:
    Corresponding author: Hu Sen, Email:
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引用本文：

高明娟, 刘维维, 王晓娜, 刘洋, 白晓东, 周方强, 刘锐, 郑金光, 赵增凯, 胡森. 丙酮酸钠羟乙基淀粉对50%总体表面积Ⅲ度烧伤大鼠肾血流量和肾功能的影响[J]. 中华损伤与修复杂志(电子版), 2015, 10(05): 388-394.

Mingjuan Gao, Weiwei Liu, Xiaona Wang, Yang Liu, Xiaodong Bai, Fangqiang Zhou, Rui Liu, Jinguang Zhen, Zengkai Zhao, Sen Hu. Effects of sodium pyruvate-hydroxyethyl starch on renal blood flow and kidney function in rats with 50% total body surface area full thickness scald injury[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2015, 10(05): 388-394.

目的

研究丙酮酸钠羟乙基淀粉(HES)胶体液对50%总体表面积(TBSA)Ⅲ度烧伤大鼠肾血流量和肾功能指标的影响。

方法

选取SD大鼠180只，100 ℃水浴烫伤制成50%TBSA Ⅲ度烧伤模型，37 ℃水浴制备假伤模型。随机数字表法分为5组：单纯烧伤组(n＝20)、假伤组(n＝40)、丙酮酸钠HES组(n＝40)、醋酸钠HES组(n＝40)和氯化钠HES组(n＝40)，其中前2组大鼠不补液，后3组(统称复苏组)伤后通过颈静脉导管补液，用微量输液泵控制输液速度。静脉补液总量为0.75 mL/kg×1% TBSA，胶晶比例1∶1，伤后12 h内输完，前4 h各复苏组输入总量的1/2均为醋酸钠林格氏液，后8 h输入总量的余1/2为相应不同胶体。单纯烧伤组于伤后4、8 h分别选取鼠10只，余4组于伤后4、8、12、24 h各时刻点选取鼠10只，激光多普勒血流仪测定肾血流量(RBF)，全自动生化分析仪测定血浆中肌酐和尿素氮含量。采用SPSS17. 0统计软件包分析，组间两两比较采用单因素方差分析。

结果

伤后4、8 h，单纯烧伤组大鼠RBF(32.10±6.40、11.80±5.43)BPU较假伤组(146.50±23.73、144.80±24.27)BPU降低，差异有统计学意义(P<0.05)；伤后4、8、12、24 h，丙酮酸钠HES组、醋酸钠HES组、氯化钠HES组大鼠RBF分别为(46.40±8.14、104.80±22.75、89.40±12.07、77.10±10.78)、(45.50±8.21、77.20±13.19、70.60±10.55、56.90±8.49)、(45.30±8.76、58.10±11.32、51.70±9.65、40.20±8.25)BPU，均较假伤组(146.50±23.73、144.80±24.27、147.60±26.55、143.20±23.94)BPU明显降低，差异均有统计学意义(P均小于0.05)；伤后8、12、24 h，丙酮酸钠HES组RBF均高于醋酸钠HES组和氯化钠HES组，醋酸钠HES组又高于氯化钠HES组，差异均有统计学意义(P均小于0.05)。伤后24 h，丙酮酸钠HES组血浆肌酐(66.70±6.67) μmol/L显著低于醋酸钠HES组(80.20±9.97) μmol/L和氯化钠HES组(91.30±9.50)μmol/L,差异均有统计学意义(P均小于0.05),丙酮酸钠HES组尿素氮(29.00±2.48) mmol/L显著低于醋酸钠HES组(34.60±3.11)mmol/L和氯化钠HES组(44.40±4.89)mmol/L,差异均有统计学意义(P均小于0.05)。

结论

严重烧伤大鼠静脉复苏时，HES 130/0.4的载体溶液对肾功能有明显的影响，丙酮酸钠HES能显著改善50%TBSA烧伤大鼠RBF和肾功能指标，优于常用的氯化钠HES和醋酸钠HES。

关键词: 羟乙基淀粉, 烧伤, 缺血, 肾血流量，有效, 肾功能, 丙酮酸钠
Objective

To study the effects of pyruvate-containing hydroxyethyl starch (HES 130/0.4) on renal blood flow and kidney function in rats subjected with 50% total body surface area Ⅲ degree burns.

Methods

One hundred and eighty SD rats, of which 160 rats were subjected to a 50% total body surface area burn, were divided into five groups: burns without fluid resuscitation(n=20), shame control group(n=40), burns with pyruvate-containing hydroxyethyl starch group (n=40), burns with acetate-containing hydroxyethyl starch group (n=40), and burns with normal saline-containing hydroxyethyl starch group (n=40), the front two groups were no resuscition, otherwise fluid infusion was taken via the jugular vein catheter to the after groups, using a trace infusion pump controlled theinfusion speed. The total amount of fluids infused was 0.75 ml/kg × 1% total body surface area (1/2 colloidal rehydration formula) of various hydroxyethyl starch and the equal volume of acetated Ringer′s solution with the colloid to crystalloid ratio of 1∶1 within 12 h post-resuscittion burns. Burn in 4 h with acetated Ringer′s solution, then in after 8 h with different colloid. Each group was further divided into four subgroups: 4 h, 8 h, 12 h, and 24 h after scald (n=10). Laser doppler blood flow meter determination of renal blood flow, automatic biochemical analyzer of creatinine and urea nitrogen content in the blood plasma were measured. SPSS 17.0 statistical software package be used to analyze the data, with two comparison using single factor analysis of variance between groups.

Results

At 4 h and 8 h after burns, the renal blood flow level in burns without fluid resuscitation (32.10±6.40, 11.80±5.43) BPU of rats were lower than those in shame control group (146.50±23.73, 144.80±24.27) BUP, the difference was statistically significant (P<0.05); At 4 h, 8 h, 12 h and 24 h after burns, the renal blood flow of burns with pyruvate-containing hydroxyethyl starch group, burns with acetate-containing hydroxyethyl starch group, and burns with normal saline-containing hydroxyethyl starch group were(46.40±8.14, 104.80±22.75, 89.40±12.07, 77.10±10.78), (45.50±8.21, 77.20±13.19, 70.60±10.55, 56.90±8.49), (45.30±8.76, 58.10±11.32, 51.70±9.65, 40.20±8.25)BPU, which were all significantly lower than those in shame control group(146.50±23.73, 144.80±24.27, 147.60±26.55, 143.20±23.94)BPU, the difference was statistically significant (P<0.05); At 8 h, 12 h and 24 h after burns, the renal blood flow of burns with pyruvate-containing hydroxyethyl starch group was higher than burns with acetate-containing hydroxyethyl starch group and burns with normal saline-containing hydroxyethyl starch group, and burns with acetate-containing hydroxyethyl starch group was higher than burns with normal saline-containing hydroxyethyl starch group, the difference was statistically significant(P<0.05). At 24 h after burns, the Cr level of burns with pyruvate-containing hydroxyethyl starch group was(66.70±6.67)μmol/L, which was significantly lower than burns with acetate-containing hydroxyethyl starch group(80.20±9.97)μmol/L and normal saline-containing hydroxyethyl starch group (91.30±9.50) μmol/L(P<0.05), the difference was statistically significant(P<0.05); and BUN of pyruvate-containing hydroxyethyl starch group was (29.00±2.48) mmol/L, which was also significantly lower than, the difference was statistically significant(P<0.05).

Conclusions

The carrier of HES 130/0.4 played a critical role in renal blood flow and kidney function in resuscitation of rats subjected with 50% total body surface area Ⅲ burns. The sodium pyruvate-containing hydroxyethyl starch might be superior to sodium acetate and normal saline-containing hydroxyethyl starch in preservation of kidney functionduring fluid resuscitation in rats with severe burn injury.

Key words: Hetastarch, Burns, Ischemia, Renal blood flow, effective, Kidney function, Pyruvate
表1 各组50%TBSA烧伤大鼠伤后各时刻点RBF测定结果比较(BPU, ±s, n＝10)
组别 伤后4 h 伤后8 h 伤后12 h 伤后24 h
单纯烧伤组 32.10±6.40 11.80±5.43 － －
假伤组 146.50±23.73 144.80±24.27 147.60±26.55 143.20±23.94
丙酮酸钠HES组 46.40±8.14 104.80±22.75 89.40±12.07 77.10±10.78
醋酸钠HES组 45.50±8.21 77.20±13.19 70.60±10.55 56.90±8.49
氯化钠HES组 45.30±8.76 58.10±11.32 51.70±9.65 40.20±8.25
t1值 23.33 27.13 ? ?
P1值 <0.01 <0.01 ? ?
t2值 20.42 8.16 12.89 14.27
P2值 <0.01 <0.01 <0.01 <0.01
t3值 20.60 13.79 15.71 17.60
P3值 <0.01 <0.01 <0.01 <0.01
t4值 20.64 16.87 19.56 20.36
P4值 <0.01 <0.01 <0.01 <0.01
t5值 2.92 18.97 ? ?
P5值 <0.01 <0.01 ? ?
t6值 2.73 13.34 ? ?
P6值 <0.01 <0.01 ? ?
t7值 2.69 10.26 ? ?
P7值 <0.01 <0.01 ? ?
t8值 0.18 5.63 2.82 3.33
P8值 0.05 <0.01 <0.05 <0.01
t9值 0.22 8.71 6.67 6.07
P9值 >0.05 <0.01 <0.01 <0.01
t10组 0.04 3.08 3.85 2.75
P10组 >0.05 <0.05 <0.01 <0.05
表2 各组50%TBSA烧伤大鼠伤后各时刻点血浆肌酐的含量变化(μmol/L, ±s, n＝10)
组别 伤后4 h 伤后8 h 伤后12 h 伤后24 h
单纯烧伤组 52.70±4.03 108.30±17.66 － －
假伤组 20.20±2.97 21.40±3.08 21.80±3.01 22.10±2.93
丙酮酸钠HES组 36.70±3.56 45.50±4.07 53.20±6.73 66.70±6.67
醋酸钠HES组 37.40±3.19 48.30±4.63 57.70±7.33 80.20±9.97
氯化钠HES组 36.70±3.71 50.70±5.67 61.30±7.22 91.30±9.50
t1值 9.93 26.56 ? ?
P1值 <0.01 <0.01 ? ?
t2值 5.04 7.37 9.60 13.63
P2值 <0.01 <0.01 <0.01 <0.01
t3值 5.26 8.22 10.97 17.76
P3值 <0.01 <0.01 <0.01 <0.01
t4值 5.04 8.96 12.07 21.15
P4值 <0.01 <0.01 <0.01 <0.01
t5值 4.89 19.19 ? ?
P5值 <0.01 <0.01 ? ?
t6值 4.68 18.34 ? ?
P6值 <0.01 <0.01 ? ?
t7值 4.89 17.61 ? ?
P7值 <0.01 <0.01 ? ?
t8值 0.21 8.86 1.38 4.13
P8值 >0.05 >0.05 >0.05 <0.01
t9值 0.01 1.59 2.48 7.52
P9值 >0.05 >0.05 >0.05 <0.01
t10组 0.21 0.73 1.10 3.39
P10组 >0.05 >0.05 >0.05 <0.01
表3 各组50%TBSA烧伤大鼠伤后各时刻点血浆尿素氮的含量变化(mmol/L, ±s, n＝10)
组别 伤后4 h 伤后8 h 伤后12 h 伤后24 h
单纯烧伤组 31.20±2.70 52.70±5.74 － －
假伤组 8.90±0.94 8.40±1.03 8.70±0.72 9.40±1.21
丙酮酸钠HES组 24.80±2.84 21.90±1.31 24.50±1.95 29.00±2.48
醋酸钠HES组 23.50±1.83 22.50±2.28 25.70±1.53 34.60±3.11
氯化钠HES组 24.40±2.03 24.50±2.57 26.80±2.93 44.40±4.89
t1值 8.61 15.51 ? ?
P1值 <0.01 <0.01 ? ?
t2值 5.63 4.60 5.59 6.98
P2值 <0.01 <0.01 <0.01 <0.01
t3值 5.17 4.82 6.02 9.99
P3值 <0.01 <0.01 <0.01 <0.01
t4值 5.49 5.53 7.11 13.11
P4值 <0.01 <0.01 <0.01 <0.01
t5值 2.98 10.91 ? ?
P5值 <0.01 <0.01 ? ?
t6值 3.44 10.70 ? ?
P6值 <0.01 <0.01 ? ?
t7值 3.12 9.99 ? ?
P7值 <0.01 <0.01 ? ?
t8值 0.46 0.21 0.43 3.01
P8值 >0.05 >0.05 >0.05 <0.05
t9值 0.14 0.92 1.52 6.13
P9值 >0.05 >0.05 >0.05 <0.01
t10组 0.32 0.71 1.10 3.12
P10组 >0.01 >0.05 >0.05 <0.01
1
Kancir AS, Pleckaitiene L, Hansen TB, et al. Lack of nephrotoxicity by 6% hydroxyethyl starch 130/0.4 during hip arthroplasty: a randomized controlled trial[J]. Anesthesiology, 2014, 121(5): 948-958.
2
Rossaint J, Berger C, Kraft F, et al. Hydroxyethyl starch 130/0.4 decreased inflammation, neutrophil recruitment, and neutrophil extracellular trap formation[J]. Br J Anaesth, 2015, 114(3): 509-519.
3
Perner A, Haase N, Winkel P, et al. Long-term outcomes in patients with severe sepsis randomised to resuscitation with hydroxyethyl starch 130/0.42 or Ringer′s acetate[J]. Intensive Care Med, 2014, 40(7): 927-934.
4
Estrada CA, Murugan R. Hydroxyethyl starch in severe sepsis: end of starch era[J]. Crit Care, 2013, 17(2): 310.
5
罗高兴，彭毅志，吴军. 建议暂停羟乙基淀粉在严重烧伤休克期中的应用[J]. 中华烧伤杂志，2013, 29(5): 421-423.
6
Almac E, Aksu U, Bezemer R, et al. The acute effects of acetate-balanced colloid and crystalloid resuscitation on renal oxygenation in a rat model of hemorrhagic shock[J]. Resuscitation, 2012, 83(9): 1166-1172.
7
Aksu U, Bezemer R, Demirci C, et al. Acute effects of balanced versus unbalanced colloid resuscitation on renal macrocirculatory and microcirculatory perfusion during endotoxemic shock[J]. Shock, 2012, 37(2): 205-209.
8
Yu W, Hu S, Xie ZY, et al. Pyruvate oral rehydration solution improved visceral function and survival in shock rats[J]. J Surg Res, 2015, 193(1): 344-354.
9
孟祥熙，李娟，白晓东，等. 丙酮酸钠林格液对50%总体表面积烧伤休克犬静脉补液时血液动力学和器官功能的影响[J]. 中华危重病急救医学，2014, 26(4): 244-248.
10
Flaherty DC, Hoxha B, Sun J, et al. Pyruvate-fortified fluid resuscitation improves hemodynamic stability while suppressing systemic inflammation and myocardial oxidative stress after hemorrhagic shock[J]. Mil Med, 2010, 175(3): 166-172.
11
Zager RA, Johnson AC, Becker K. Renal cortical pyruvate depletion during AKI[J]. J Am Soc Nephrol, 2014, 25(5): 998-1012.
12
Béchir M, Puhan MA, Fasshauer M, et al. Early fluid resuscitation with hydroxyethyl starch 130/0.4 (6%) in severe burn injury: a randomized, controlled, double-blind clinical trial[J]. Crit Care, 2013, 17(6): R299.
13
Navickis RJ, Haynes GR, Wilkes MM. Effect of hydroxyethyl starch on bleeding after cardiopulmonary bypass: a meta-analysis of randomized trials[J]. J Thorac Cardiovasc Surg, 2012, 144(1): 223-230.
14
Wilkes NJ, Woolf R, Mutch M, et al. The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients[J]. Anesth Analg, 2001, 93(4): 811-816.
15
张元芳，吴肇光，周方强. 丙酮酸钠在缺氧型乳酸性酸中毒中的潜在临床应用[J]. 中华医学杂志，2015, 95(12): 958-960.
16
Boussekey N, Darmon R, Langlois J, et al. Resuscitation with low volume hydroxyethylstarch 130 kDa/0.4 is not associated with acute kidney injury[J]. Crit Care, 2010, 14(2): R40.
17
Ertmer C, Kampmeier TG, Rehberg S, et al. Effects of balanced crystalloid vs. 0.9% saline-based vs. balanced 6% tetrastarch infusion on renal function and tubular integrity in ovine endotoxemic shock[J]. Crit Care Med, 2011, 39(4): 783-792.
18
Cherry BH, Nguyen AQ, Hollrah RA, et al. Pyruvate stabilizes electrocardiographic and hemodynamic function in pigs recovering from cardiac arrest[J]. Exp Biol Med (Maywood), 2015.
19
Zilberter Y, Gubkina O, Ivanov AI. A unique array of neuroprotective effects of pyruvate in neuropathology[J]. Front Neurosci, 2015, 9: 17.
20
Salahudeen AK, Clark EC, Nath KA. Hydrogen peroxide-induced renal injury. A protective role for pyruvate in vitro and in vivo[J]. J Clin Invest, 1991, 88(6): 1886-1893.
21
韩晓春，胡森，刘先奇，等. 丙酮酸钠液对烫伤休克大鼠肾血管通透性的影响[J]. 中国医学工程，2011, 19(4): 4-6.
22
Hu S, Lin ZL, Zhao ZK, et al. Pyruvate Is Superior to Citrate in Oral Rehydration Solution in the Protection of Intestine via Hypoxia-Inducible Factor-1 Activation in Rats With Burn Injury[J]. JPEN J Parenter Enteral Nutr, 2015.
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