Protective effect of icariin on brain-death induced kidney injury and its mechanisms in rats

doi:10.3877/cma.j.issn.1674-3903.2017.03.004

Abstract

Abstract:

Objective

To investigate the protective effect of icariin on brain-death induced kidney injury in rats and its mechanisms.

Methods

Thirty SD rats were randomly divided into three groups, including sham group, control group (brain death) and experiment group (brain death with icariin treatment). Icariin was intraperitoneally given at the dose of 100 mg/kg right after brain death. Sham group were anaesthetized and treated with mechanical ventilation for 6 hours at the condition of normal intracranial pressure. The rats in control group and experiment group were sacrificed 6 hours after brain death and rats in sham group were sacrificed 6 hours after mechanical ventilation, and peripheral blood and kidneys were collected and detected. Measurement data was represented as (±s). One-way analysis of variance was used to compare serum creatinine, urea nitrogen, Paller score, CD68⁺ macrophage count and transcriptional levels of proinflammatory factors (IL-1β, IL-6, TNF-α) and chemokines (MCP-1, IP-10) among the 3 groups, least significant difference method was used to compare the above indexes between any two groups, difference was statistically significant when P<0.05.

Results

The levels of serum urine nitrogen and creatinine in experiment group were (10.0±1.5) and (92±12) mmol/L, respectively, which were significantly lower than control group and higher than sham group (P all<0.05). Icariin decreased the paller scores of tubular injury and alleviated mitochondria and endoplasmic reticulum injury. Icariin significantly decreased the mRNA levels of proinflammatory factors (IL-1β, IL-6, TNF-α) and chemokines (MCP-1, IP-10) , infiltration degree of macrophages, and phosphorylation levels of JNK, p38-MAPK and STAT3 in kidney tissues of experiment group.

Conclusions

Icariin protects renal function by alleviation of brain-death induced kidney injury, which might by inhibition of inflammation and SAPK and JAK-STAT signal pathways.

Key words: Brain death, Inflammatory injury, Icariin, Signal pathway

Yanfeng Liu, Yunyi Xiong, Dong Wang, Wenfang Chen, Qiao Su, Wenwen Li, Huiting Huang, Longshan Liu, Changxi Wang. Protective effect of icariin on brain-death induced kidney injury and its mechanisms in rats[J]. Chinese Journal of Transplantation(Electronic Edition), 2017, 11(03): 143-147.

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Figures/Tables 6

References 18

1	Li Y,Li J,Fu Q, et al. Kidney transplantation from brain-dead donors: initial experience in China[J]. Transplant Proc, 2016, 48(8): 2592-2595.
2	Wang C,Liu L,Fu Q, et al. Kidney transplantation from donors after brain or cardiac death in China-a clinical analysis of 94 cases[J]. Transplant Proc, 2013, 45(4): 1323-1326.
3	Maciel CB,Greer DM. ICU management of the potential organ donor: state of the art[J]. Curr Neurol Neurosci Rep, 2016, 16(9): 86.
4	Westendorp WH,Leuvenink HG,Ploeg RJ. Brain death induced renal injury[J]. Curr Opin Organ Transplant, 2011, 16(2): 151-156.
5	Hart A,Smith JM,Skeans MA, et al. OPTN/SRTR 2015 Annual Data Report: Kidney[J]. Am J Transplant, 2017, 17(Suppl 1): 21-116.
6	李梨,吴芹,周岐新, 等. 淫羊藿苷对氧自由基所致大鼠脑线粒体损伤的保护作用[J]. 中国药理学与毒理学杂志, 2005, 19(5): 333-337.
7	向家培,赵劲波,王勇, 等. 淫羊藿苷对大鼠心肌细胞缺氧再复氧损伤的作用及机制[J]. 中华医学杂志, 2015, 95(45): 3701-3704.
8	丰贵文,刘龙山,尚文俊. 淫羊藿苷对大鼠肾脏缺血再灌注后炎性损伤的保护[J]. 中国组织工程研究, 2012, 16(40): 7496-7502.
9	丰贵文,尚文俊,王跃, 等. 淫羊藿苷减轻大鼠肾脏缺血再灌注损伤的作用及机制研究[J]. 中华器官移植杂志, 2012, 33(9): 559-562.
10	Barklin A. Systemic inflammation in the brain-dead organ donor[J]. Acta Anaesthesiol Scand, 2009, 53(4): 425-435.
11	Li Y,Xiong Y,Zhang H, et al. Ginkgo biloba extract EGb761 attenuates brain death-induced renal injury by inhibiting pro-inflammatory cytokines and the SAPK and JAK-STAT signalings[J]. Sci Rep, 2017, 7: 45192.
12	应美珂,陈芷珉,王宇成, 等. 后肾间充质干细胞在小鼠肾缺血再灌注损伤中的作用[J]. 中华医学杂志, 2016, 96(20): 1573-1577.
13	Oto T,Calderone A,Li Z, et al. P38 mitogen-activated protein kinase inhibition reduces inflammatory cytokines in a brain-dead transplant donor animal model[J]. Heart Lung Circ, 2009, 18(6): 393-400.
14	Asif S,Sedigh A,Nordstrom J, et al. Oxygen-charged HTK-F6H8 emulsion reduces ischemia-reperfusion injury in kidneys from brain-dead pigs[J]. J Surg Res, 2012, 178(2): 959-967.
15	Ma FY,Liu J,Nikolic-Paterson DJ. The role of stress-activated protein kinase signaling in renal pathophysiology[J]. Braz J Med Biol Res, 2009, 42(1): 29-37.
16	Villarino AV,Kanno Y,Ferdinand JR, et al. Mechanisms of Jak/STAT signaling in immunity and disease[J]. J Immunol, 2015, 194(1): 21-27.
17	Minambres E,Cemborain A,Sanchez-Velasco P, et al. Correlation between transcranial interleukin-6 gradient and outcome in patients with acute brain injury[J]. Crit Care Med, 2003, 31(3): 933-938.
18	Rose-John S. IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6[J]. Int J Biol Sci, 2012, 8(9): 1237-1247.

目的基因	上游引物(5’-3’)	下游引物(5’-3’)
IL-1β	ATGACCTGTTCTTTGAGGCTGAC	CTTGTCGAGATGCTGCTGTGA
IL-6	AACTCCATCTGCCCTTCAGGAACA	AAGGCAGTGGCTGTCAACAACATC
TNF-α	GGTGTCTGTGCCTCAGCCTCT	GGGAACTTCTCCTCCTTGTTGG
MCP-1	GCCTGTTGTTCACAGTTGCTG	GACTCATTGGGATCATCTTGC
IP-10	TGAAAGCGGTGAGCCAAAGAA	CTGGGTAAAGGGAGGTGGAGA
β-actin	AGATTACTGCCCTGGCTCCTA	ATCGTACTCCTGCTTGCTGAT

目的基因	上游引物(5’-3’)	下游引物(5’-3’)
IL-1β	ATGACCTGTTCTTTGAGGCTGAC	CTTGTCGAGATGCTGCTGTGA
IL-6	AACTCCATCTGCCCTTCAGGAACA	AAGGCAGTGGCTGTCAACAACATC
TNF-α	GGTGTCTGTGCCTCAGCCTCT	GGGAACTTCTCCTCCTTGTTGG
MCP-1	GCCTGTTGTTCACAGTTGCTG	GACTCATTGGGATCATCTTGC
IP-10	TGAAAGCGGTGAGCCAAAGAA	CTGGGTAAAGGGAGGTGGAGA
β-actin	AGATTACTGCCCTGGCTCCTA	ATCGTACTCCTGCTTGCTGAT

组别	只数	血清肌酐(mmol/L)	血清尿素氮(mmol/L)	Paller评分(分)
脑死亡组	10	121±15^a	12.4±1.9^a	242±42^a
治疗组	10	92±12^ab	10.0±1.5^ab	1 680±240^ab
假手术组	10	43±12	4.2±1.1	50±100

组别	只数	血清肌酐(mmol/L)	血清尿素氮(mmol/L)	Paller评分(分)
脑死亡组	10	121±15^a	12.4±1.9^a	242±42^a
治疗组	10	92±12^ab	10.0±1.5^ab	1 680±240^ab
假手术组	10	43±12	4.2±1.1	50±100

组别	只数	IL-1β	IL-6	TNF-α	MCP-1	IP-10	CD68^＋(个)
脑死亡组	10	9.4±1.67^a	12.8±3.24^a	3.8±1.39^a	4.2±1.55^a	22.1±3.41^a	46.7±10.2^a
治疗组	10	5.1±0.73^ab	5.5±1.65^ab	2.5±0.81^ab	2.4±0.64^ab	8.3±2.58^ab	18.7±3.3^ab
假手术组	10	1.0±0.14	1.0±0.15	1.0±0.27	1.0±0.24	1.0±0.20	3.8±2.9

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