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. 2015 Dec 14;10(12):e0144516.
doi: 10.1371/journal.pone.0144516. eCollection 2015.

Ulinastatin Protects against Acute Kidney Injury in Infant Piglets Model Undergoing Surgery on Hypothermic Low-Flow Cardiopulmonary Bypass

Xiaocou Wang  1   2 , Qinghua Xue  2 , Fuxia Yan  2 , Jinping Liu  3 , Shoujun Li  4 , Shengshou Hu  4
Affiliations

Ulinastatin Protects against Acute Kidney Injury in Infant Piglets Model Undergoing Surgery on Hypothermic Low-Flow Cardiopulmonary Bypass

Xiaocou Wang et al. PLoS One. .

Abstract

Objective: Infants are more vulnerable to kidney injuries induced by inflammatory response syndrome and ischemia-reperfusion injury following cardiopulmonary bypass especially with prolonged hypothermic low-flow (HLF). This study aims to evaluate the protective role of ulinastatin, an anti-inflammatory agent, against acute kidney injuries in infant piglets model undergoing surgery on HLF cardiopulmonary bypass.

Methods: Eighteen general-type infant piglets were randomly separated into the ulinastatin group (Group U, n = 6), the control group (Group C, n = 6), and the sham operation group (Group S, n = 6), and anaesthetized. The groups U and C received following experimental procedure: median thoracotomy, routine CPB and HLF, and finally weaned from CPB. The group S only underwent sham median thoracotomy. Ulinastatin at a dose of 5,000 units/kg body weight and a certain volume of saline were administrated to animals of the groups U and C at the beginning of CPB and at aortic declamping, respectively. Venous blood samples were collected at 3 different time points: after anesthesia induction in all experimental groups, 5 minutes, and 120 minutes after CPB in the Groups U and C. Markers for inflammation and acute kidney injury were tested in the collected plasma. N-acetyl-β-D-glucosaminidase (NAG) from urine, markers of oxidative stress injury and TUNEL-positive cells in kidney tissues were also detected.

Results: The expressions of plasma inflammatory markers and acute kidney injury markers increased both in Group U and Group C at 5 min and 120 min after CPB. Also, numbers of TUNEL-positive cells and oxidative stress markers in kidney rose in both groups. At the time point of 120-min after CPB, compared with the Group C, some plasma inflammatory and acute kidney injury markers as well as TUNEL-positive cells and oxidative stress markers in kidney were significantly reduced in the Group U. Histologic analyses showed that HLF promoted acute tubular necrosis and dilatation.

Conclusions: HLF cardiopulmonary bypass surgery could intensify systemic inflammatory responses and oxidative stress on infant piglets, thus causing acute kidney injury. Ulinastatin might reduce such inflammatory response and oxidative stress and the extent of kidney injury.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Results of plasma markers of inflammation in the three groups.
(A) serum IL-6, interleukin-6; (B) serum TNF-α, tumor necrosis factor-α. Data are presented as mean±SD, n = 6, *P <0.05 versus Group C. For graphs pooled estimates for pairwise comparisons derived from Analysis of Covariance with adjustment for baseline serum IL-6 at 0.94±0.13μg/L, serum TNF-α 0.32±0.05ng/L, were as follows: IL-6; 5min post CPB(T2): Group C, 1.37±0.16μg/L, Group U, 1.01±0.13μg/L. Test for overall treatment effect p = 0.021. 120min post CPB(T3): Group C, 1.38±0.28μg/L, Group U, 1.13±0.24μg/L. Test for overall treatment effect P = 0.001. TNF-α; 5min post CPB(T2): Group C, 0.37±0.19 ng/L, Group U, 0.33±0.19ng/L. Test for overall treatment effect P = 0.075. 120min post CPB(T3): Group C, 0.35±0.13 ng/L, Group U, 0.32±0.13 ng/L. Test for overall treatment effect P = 0.088.
Fig 2
Fig 2. Results of markers of kidney injury in the three groups.
(A) serum creatinine; (B) serum BUN; (C) serum CysC; (D) urine NAG, urine N-acetyl-β-D-glucosaminidase. Data are presented as mean±SD, n = 6, *P <0.05 versus Group C, ΨP <0.05 versus Group S. For graphs pooled estimates for pairwise comparisons derived from Analysis of Covariance with adjustment for baseline serum creatinine at 53.61±9.53μmmol/L, serum BUN 4.31±1.34μmmol/L, serum CysC 24.35±4.2μg/L, were as follows: serum creatinine; 5min post CPB(T2): Group C, 64.24±12.53μmmol/L, Group U, 62.33±11.73μmmol/L. Test for overall treatment effect P = 0.074. 120min post CPB(T3): Group C, 86.62±11.41μmmol/L, Group U, 71.72±12.55μmmol/L. Test for overall treatment effect P = 0.032. serum BUN; 5min post CPB(T2): Group C, 5.43±1.87μmmol/L, Group U, 5.41±1.72μmmol/L. Test for overall treatment effect P = 0.081. 120min post CPB(T3): Group C, 7.37±1.72μmmol/L, Group U, 6.13±1.69μmmol/L. Test for overall treatment effect P = 0.025. serum CysC; 5min post CPB(T2): Group C, 30.47±4.4μg/L, Group U, 26.66±5.7μg/L. Test for overall treatment effect P = 0.069. 120min post CPB(T3): Group C, 40.62±6.5μg/L, Group U, 30.72±6.2μg/L. Test for overall treatment effect P = 0.001.
Fig 3
Fig 3. Typical histological examination results in the three groups.
A, Group S, Tubules and glomeruli appear normal (H&E×400); B, Group C, after 2h CPB, kidney histologic changes include tubular dilatation(*), vacuole formation(▲), and glomerular over-filling (arrow) appeared obvious (H&E×400); C, Group U, injury changes of kidney still exist as tubular dilatation(*), vacuole formation(▲), and glomerular over-filling (arrow) but were milder with intervention of ulinastatin(H&E×400).
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References

    1. Pastuszko P, Schears GJ, Pirzadeh A, Kubin J, Greeley WJ, Wilson DF, et al. (2012) Effect of granulocyte-colony stimulating factor on expression of selected proteins involved in regulation of apoptosis in the brain of newborn piglets after cardiopulmonary bypass and deep hypothermic circulatory arrest. J Thorac Cardiovasc Surg 143:1436–1442. 10.1016/j.jtcvs.2012.01.018 - DOI - PMC - PubMed
    1. Nguyen B, Luong L, Naase H, Vives M, Jakaj G, Finch J, et al. (2014) Sulforaphane pretreatment prevents systemic inflammation and renal injury in response to cardiopulmonary bypass. J Thorac Cardiovasc Surg 148:690–697.e3. 10.1016/j.jtcvs.2013.12.048 - DOI - PubMed
    1. Day JR, Taylor KM (2005) The systemic inflammatory response syndrome and cardiopulmonary bypass. Int J Surg 3:129–140. - PubMed
    1. Zhu J, Yin R, Shao H, Dong G, Luo L, Jing H (2007) N-acetylcysteine to ameliorate acute renal injury in a rat cardiopulmonary bypass model. J Thorac Cardiovasc Surg 133:696–703. - PubMed
    1. Kumar AB, Suneja M, Bayman EO, Weide GD, Tarasi M (2012) Association between postoperative acute kidney injury and duration of cardiopulmonary bypass: a meta-analysis. J Cardiothorac Vasc Anesth 26:64–69. 10.1053/j.jvca.2011.07.007 - DOI - PubMed

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This research was supported by a grant funded from the National Key Basic Research Development Program (973 Program) and by a project funded by the Ministry of Science and Technology of People's Republic of China (Project name: Basic research of congenital heart disease formation, development and intervention; Grant Recipient: Shengshou Hu; Grant Number: 2010CB529507; [http://www.most.gov.cn/]).