Protective effect of ulinastatin on liver and its mechanism of inhibiting hepatocyte apoptosis in septic rats

doi:10.3877/cma.j.issn.1674-6880.2017.02.002

Abstract

Abstract:

Objective

To investigate the protective effect of ulinastatin on liver and its mechanism of inhibiting hepatocyte apoptosis in septic rats.

Methods

A total of 30 male SD rats were randomly divided into the sham group, sepsis group and ulinastatin group, 10 rats in each group. The model of sepsis was reproduced by cecal ligation and puncture (CLP), and rats in the sham group received celiotomy without ligation and puncture. Rats in the ulinastatin group were given ulinastatin by tail vein injection (200 000 U/kg) on 15 min after laparotomy, and rats in the sham group and sepsis group were injected with equivalence saline. The levels of interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA) on 6, 12, 24 h after laparotomy. The liver tissue was observed by hematoxylin and eosin (HE) on 24 h after laparotomy. The apoptosis protein Bax and Bcl-2 and Caspase-3 expression in hepatic tissue were determined by immunohistochemistry.

Results

The levels of IL-1β (F = 5.723, P = 0.018; F = 12.969, P < 0.001; F = 4.956, P = 0.027) and TNF-α (F = 5.618, P = 0.020; F = 20.002, P < 0.001; F = 17.869, P < 0.001) in the ulinastatin group and sepsis group on 6, 12, 24 h after laparotomy were all much higher than those in the sham group, and were highest in the sepsis group. HE staining found that hepatocyte swelling obviously, inflammatory cellular infiltration at portal areas in the sepsis group, and hepatocyte and hepatic lobule only mild damage in the ulinastatin group. Meanwhile, the expression of Bax [(17.6 ± 2.2), (30.2 ± 4.2), (1.5 ± 0.8)] and Caspase-3 [(10.54 ± 1.44), (22.60 ± 1.86), (0.86 ± 0.24)] in the ulinastatin group and sepsis group increased markedly, the Bcl-2 [(21.6 ± 1.6), (10.2 ± 1.5), (42.4 ± 2.9)] decreased markedlyas compared with the sham group, and the expression of Bax and Caspase-3 increased most and Bcl-2 decreased most in the sepsis group (all P < 0.05).

Conclusion

Ulinastatin can protect the hepatocytes of rats with sepsis by inhibiting the inflammatory reaction and hepatocyte apoptosis.

Key words: Oral ulcer, Gels, Matrine, Bioadhesive gel, Rabbits

Xuejiao Li, Junjie Chen, Lei Wang, Lifeng Wang, Jian Kang, Yongning Li. Protective effect of ulinastatin on liver and its mechanism of inhibiting hepatocyte apoptosis in septic rats[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2017, 10(02): 76-81.

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Figures/Tables 5

References 24

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组别	只数	IL-1β			TNF-α
组别	只数	6 h	12 h	24 h	6 h	12 h	24 h
假手术组	10	41.3 ± 1.5	42.2 ± 1.5	39.8 ± 1.6	80.6 ± 2.1	79.6 ± 1.9	78.6 ± 1.5
脓毒症组	10	92.6 ± 2.5^a	142.6 ± 2.8^a	125.3 ± 2.5^a	252.6 ± 14.6^a	302.6 ± 18.5^a	246.3 ± 13.7^a
乌司他丁组	10	56.4 ± 1.8^ab	85.2 ± 2.2^ab	76.7 ± 1.7^ab	122.6 ± 12.2^ab	160.4 ± 14.3^ab	108.4 ± 9.2^ab
F值	?	5.723	12.969	4.956	5.618	20.002	17.869
P值	?	0.018	<0.001	0.027	0.020	<0.001	<0.001

组别	只数	IL-1β			TNF-α
组别	只数	6 h	12 h	24 h	6 h	12 h	24 h
假手术组	10	41.3 ± 1.5	42.2 ± 1.5	39.8 ± 1.6	80.6 ± 2.1	79.6 ± 1.9	78.6 ± 1.5
脓毒症组	10	92.6 ± 2.5^a	142.6 ± 2.8^a	125.3 ± 2.5^a	252.6 ± 14.6^a	302.6 ± 18.5^a	246.3 ± 13.7^a
乌司他丁组	10	56.4 ± 1.8^ab	85.2 ± 2.2^ab	76.7 ± 1.7^ab	122.6 ± 12.2^ab	160.4 ± 14.3^ab	108.4 ± 9.2^ab
F值	?	5.723	12.969	4.956	5.618	20.002	17.869
P值	?	0.018	<0.001	0.027	0.020	<0.001	<0.001

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