Effect of xuebijing injection on tubular apoptosis and related proteins expression in rat model of sepsis-induced acute kidney injury

doi:10.3877/cma.j.issn.1674-6880.2016.05.006

Abstract

Abstract:

Objective

To investigate the effect of early application of xuebijing in rat model of sepsis-induced acute kidney injury by observing tubular apoptosis, B cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) expressions.

Methods

Fifty-four male SD rats were randomly divided into three groups: Sham group (n = 18), cecal ligation and puncture (CLP) group (n = 18), and xuebijing (CLP + XBJ) group (n = 18). After rat model establishment, 12, 24, 48 h were regarded as observation time points, and each group was accordingly divided into 3 subgroups (6 rats per subgroup). Creatine clearance (CrCl), renal blood perfusion unit, renal pathological changes and renal tubular injury score were measured; renal tubular cell apoptosis was determined by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) method and integrated optical density (IOD) was calculated. The expressions of Bcl-2 and Bax were detected by Western-blotting.

Results

The CrCl and renal blood perfusion unit in all three groups had significant differences at each time point (F = 6.405, 18.821; P < 0.05). The CrCl and renal blood perfusion unit in the CLP + XBJ group were significantly higher than that in the CLP group [(2.1 ± 0.5) ml/min/100 g vs. (1.1 ± 0.3) ml/min/100 g, (159 ± 38) BPU vs. (79 ± 32) BPU; all P < 0.05]. The renal tubular damage scores in all three groups had significant differences at each time point (F = 5.461, P < 0.05). Tubular damage scores decreased significantly in the CLP + XBJ group compared with the CLP group at 24, 48 h [(1.6 ± 0.5) vs. (2.8 ± 0.8), (1.8 ± 0.8) vs. (3.6 ± 0.6); all P < 0.05]. The IOD had a significant difference in all three groups at each time point (F = 7.259, P < 0.05). In addition, the IOD in the CLP + XBJ group was much lower than that in the CLP group at each time point [(26.6 ± 6.9) vs. (34.4 ± 5.0), (38.2 ± 5.3) vs. (48.0 ± 5.8), (37.6 ± 2.2) vs. (53.8 ± 6.7); all P < 0.05]. Meanwhile, xuebijing injection could increase Bcl-2 expression, inhibit Bax expression, and keep balance of Bcl-2/Bax ratio. There were significant differences of Bcl-2 [(1.30 ± 0.09) vs. (0.76 ± 0.09), (2.12 ± 0.38) vs. (0.51 ± 0.07); all P < 0.05] and Bax [(1.19 ± 0.37) vs. (1.95 ± 0.90), (1.48 ± 0.15) vs. (2.69 ± 0.39); all P < 0.05] in the CLP + XBJ group compared with the CLP group at 24 and 48 h.

Conclusion

Early application of xuebijing might improve renal dysfunction and the pathological changes, reduce the tubular cell apoptosis, keep balance of Bcl-2/Bax ratio and relieve renal impairment in rat model of sepsis-induced acute kidney injury.

Key words: Sepsis, Apoptosis, Xuebijing, Acute kidney injury

Xuedong Sun, Yihe Yan, Fang Liu, Weiwei Chu, Yiting Zhang, Lijun Ying. Effect of xuebijing injection on tubular apoptosis and related proteins expression in rat model of sepsis-induced acute kidney injury[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2016, 09(05): 315-320.

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Figures/Tables 7

References 18

1	Wan L,Bagshaw SM,Langenberg C, et al. Pathoph-ysiology of septic acute kidney injury: what do we really know?[J]. Crit Care Med, 2008, 36(4 Suppl): S198-S203.
2	Holthoff JH,Wang Z,Seely KA, et al. Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury[J]. Kidney Int, 2012, 81(4): 370-378.
3	程星,曹丽萍,乔佑杰, 等. 腹腔注射血必净对脓毒症急性肾损伤大鼠肾功能的影响及机制探讨[J]. 山东医药, 2015, 5(23)：28-30.
4	Rittirsch D,Huber-Lang MS,Flierl MA, et al. Immunodesign of experimental sepsis by cecal ligation and puncture[J]. Nat Protoc, 2009, 4(1): 31-36.
5	Langenberg C,Bagshaw SM,May CN, et al. The histopathology of septic acute kidney injury: a systematic review[J]. Crit Care, 2008, 12(2): R38-R45.
6	臧芝栋,严洁. 以提高肾脏病整体预后工作组诊断标准分析脓毒症相关急性肾损伤患者的临床特点[J]. 中华内科杂志, 2013, 52(4)：299-304.
7	Choi HM,Jo SK,Kim SH, et al. Glucocorticoids attenuate septic acute kidney injury[J]. Biochem Biophys Res Commun, 2013, 435(4): 678-684.
8	Pathak E,MacMillan-Crow LA,Mayeux PR. Role of mitochondrial oxidants in an in vitro model of sepsis-induced renal injury[J]. J Pharmacol Exp Ther, 2012, 340(1): 192-201.
9	Tran M,Tam D,Bardia A, et al. PGC-1α promotes recovery after acute kidney injury during systemic inflammation in mice[J]. J Clin Invest, 2011, 121(10): 4003-14.
10	Parikh SM. Therapeutic targeting of the mitochondrial dysfunction in septic acute kidney injury [J]. Curr Opin Crit Care, 2013, 19(6): 554-559.
11	Yao W,Hu Q,Ma Y, et al. Human adipose-derived mesenchymal stem cells repair cisplatin-induced acute kidney injury through antiapoptotic pathways[J]. Exp Ther Med, 2015, 10(2): 468-476.
12	Chen LW,Chen W,Hu ZQ, et al. Protective effects of growth arrest-specific protein 6 (Gas6) on sepsis-induced acute kidney injury[J]. Inflammation, 2016, 39(2): 575-582.
13	王茹,张俊录,李月红, 等. 细胞凋亡及Bcl-2和Bax基因表达在脓毒症大鼠肾脏损伤中的作用[J]. 实用医学杂志, 2011, 27(7)：1164-1166.
14	陈敏华,孙仁华,李茜. 脓毒症伴急性肾损伤患者连续性肾脏替代治疗时机的探讨[J/CD]. 中华危重症医学杂志：电子版, 2016, 9(3)：149-153.
15	Pickkers P,Heemskerk S,Schouten J, et al. Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial[J]. Critical Care, 2011, 16(1): R14
16	Li N,Xie H,Li L, et al. Effects of honokiol on sepsis-induced acute kidney injury in an experimental model of sepsis in rats[J]. Inflammation, 2014, 37(4): 1191-1199.
17	孟东亮,邢海波,茅尧生, 等. 中性粒细胞明胶酶相关脂质运载蛋白对脓毒症继发急性肾损伤患者的早期预测价值[J/CD]. 中华危重症医学杂志：电子版, 2015, 8(4)：224-229.
18	王永明,乔佑杰,李家瑞, 等. 血必净对脓毒症大鼠巨噬细胞移动抑制因子和急性肾损伤的干预效果[J]. 天津医药, 2014, 42(10)：988-991.

组别	只数	CrCl（ml·min^-1·100 g^-1）			血流灌注量(BPU)
组别	只数	12 h	24 h	48 h	12 h	24 h	48 h
Sham组	6	1.8 ± 0.3	1.9 ± 0.8	1.8 ± 0.6	185 ± 22	195 ± 20	189 ± 19
CLP组	6	1.8 ± 0.1	1.4 ± 0.4^ab	1.1 ± 0.3^abc	295 ± 52^a	155 ± 30^ab	79 ± 32^abc
CLP + XBJ组	6	1.7 ± 0.4	2.0 ± 0.3^bd	2.1 ± 0.5^bd	249 ± 32^a	175 ± 30^bd	159 ± 38^bcd
F值	?	6.405			18.821
P值	?	< 0.05			< 0.05

组别	只数	CrCl（ml·min^-1·100 g^-1）			血流灌注量(BPU)
组别	只数	12 h	24 h	48 h	12 h	24 h	48 h
Sham组	6	1.8 ± 0.3	1.9 ± 0.8	1.8 ± 0.6	185 ± 22	195 ± 20	189 ± 19
CLP组	6	1.8 ± 0.1	1.4 ± 0.4^ab	1.1 ± 0.3^abc	295 ± 52^a	155 ± 30^ab	79 ± 32^abc
CLP + XBJ组	6	1.7 ± 0.4	2.0 ± 0.3^bd	2.1 ± 0.5^bd	249 ± 32^a	175 ± 30^bd	159 ± 38^bcd
F值	?	6.405			18.821
P值	?	< 0.05			< 0.05

组别	只数	12 h	24 h	48 h
Sham组	6	0.5 ± 0.4	0.6 ± 0.4	0.6 ± 0.6
CLP组	6	1.4 ± 0.6^a	2.8 ± 0.8^ab	3.6 ± 0.6^abc
CLP + XBJ组	6	1.2 ± 0.4^a	1.6 ± 0.5^abd	1.8 ± 0.8^abcd
F值	?	?	5.461	?
P值	?	?	< 0.05	?

组别	只数	12 h	24 h	48 h
Sham组	6	0.5 ± 0.4	0.6 ± 0.4	0.6 ± 0.6
CLP组	6	1.4 ± 0.6^a	2.8 ± 0.8^ab	3.6 ± 0.6^abc
CLP + XBJ组	6	1.2 ± 0.4^a	1.6 ± 0.5^abd	1.8 ± 0.8^abcd
F值	?	?	5.461	?
P值	?	?	< 0.05	?

组别	只数	12 h	24 h	48 h
Sham组	6	10.4 ± 1.5	10.6 ± 2.1	10.4 ± 2.6
CLP组	6	34.4 ± 5.0^a	48.0 ± 5.8^ab	53.8 ± 6.7^abc
CLP + XBJ组	6	26.6 ± 6.9^ad	38.2 ± 5.3^abd	37.6 ± 2.2^abd
F值	?	?	7.259	?
P值	?	?	< 0.05	?

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