Protective effect of ulinastatin on acute lung injury in sepsis rats and its mechanism

doi:10.3877/cma.j.issn.1674-6880.2017.03.003

Abstract

Abstract:

Objective

To observe the effect and mechanism of ulinastatin on protecting acute lung injury (ALI) in sepsis rats induced by lipopolysaccharide (LPS).

Methods

Fifty-two rats were randomly assigned to the ulinastatin group (n = 26) and control group (n = 26). All the rats were given LPS (10 mg/kg) intraperitoneally, and rats in the ulinastatin group were injected ulinastatin (100 000 U/kg) on 18, 3 h before modeling, and rats in the control group were received equivalence saline. The levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-10 and total protein levels in bronchoalveolar lavage fluid (BALF) were detected at 0.5, 2, 4, 12, 24 and 72 h after modeling. The pathological changes in the lung tissues were observed by optical microscope.

Results

The levels of TNF-α, IL-6, IL-10 and total protein in BALF all showed significant differences between the two groups (F = 5.899, P = 0.040; F = 7.932, P = 0.029; F = 18.450, P = 0.005; F = 6.467, P = 0.038). And compared with the control group, TNF-α [(21.6 ± 3.8) ng/L vs. (14.8 ± 2.5) ng/L, (69.2 ± 3.2) ng/L vs. (48.8 ± 3.9) ng/L, (74.8 ± 6.9) ng/L vs. (56.3 ± 4.2) ng/L, (120.2 ± 43.8) ng/L vs. (106.4 ± 65.8) ng/L, (190.2 ± 30.4) ng/L vs. (119.8 ± 28.9) ng/L, (159.7 ± 10.5) ng/L vs. (112.3 ± 10.2) ng/L], IL-6 [(145 ± 6) ng/L vs. (119 ± 5) ng/L, (344 ± 19) ng/L vs. (225 ± 22) ng/L, (458 ± 36) ng/L vs. (273 ± 28) ng/L, (949 ± 64) ng/L vs. (328 ± 27) ng/L, (841 ± 61) ng/L vs. (306 ± 6) ng/L, (899 ± 35) ng/L vs. (278 ± 16) ng/L] and total protein in BALF [(320 ± 8) mg/L vs. (290 ± 17) mg/L, (400 ± 7) mg/L vs. (336 ± 9) mg/L, (536 ± 10) mg/L vs. (492 ± 14) mg/L, (806 ± 10) mg/L vs. (608 ± 17) mg/L, (781 ± 17) mg/L vs. (579 ±16) mg/L, (662 ± 24) mg/L vs. (505 ± 9) mg/L] were much lower, and the IL-10 levels [(5.7 ± 0.8) ng/L vs. (11.7 ± 0.9) ng/L, (17.2 ± 1.6) ng/L vs. (31.9 ± 2.6) ng/L, (22.3 ± 2.1) ng/L vs. (54.7 ± 4.8) ng/L, (42.3 ± 4.9) ng/L vs. (80.7 ±1.9) ng/L, (29.7 ± 1.4) ng/L vs. (69.4 ± 3.4) ng/L, (21.4 ± 2.9) ng/L vs. (74.3 ± 5.5) ng/L] were much higher in the ulinastatin group at 0.5, 2, 4, 12, 24, and 72 h (all P < 0.05). The optical microscope showed alveolar wall tissue thickening, mesenchyma hyperemia and edema, inflammatory cellular infiltration and alveolar collapse in the control group, and above pathology changes were significantly alleviated in the ulinastatin group.

Conclusion

Ulinastatin can protect sepsis rats with ALI through reducing the levels of TNF-α and IL-6, promoting IL-10 levels and thereby inhibiting the neutrophil infiltration and protease expression in the lungs.

Key words: Acute lung injury, Sepsis, Ulinastatin, Lipopolysaccharides, Rats

Huihui Zhang, Guolong Cai, Caibao Hu, Molei Yan. Protective effect of ulinastatin on acute lung injury in sepsis rats and its mechanism[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2017, 10(03): 153-158.

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Figures/Tables 3

References 20

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指标	组别	只数	0.5 h	2h	4 h	12 h	24 h	72 h
TNF-α	乌司他丁组	15	14.8 ± 2.5^a	48.8 ± 3.9^ab	56.3 ± 4.2^abc	106.4 ± 65.8^abcd	119.8 ± 28.9^abcde	112.3 ± 10.2^abcdef
?	对照组	15	21.6 ± 3.8	69.2 ± 3.2^b	74.8 ± 6.9^bc	120.2 ± 43.8^bcd	190.2 ± 30.4^bcde	159.7 ± 10.5^bcdef
IL-6	乌司他丁组	15	119 ± 5^a	225 ± 22^ab	273 ± 28^abc	328 ± 27^abcd	306 ± 6^abcde	278 ± 16^abcdef
?	对照组	15	145 ± 6	344 ± 19^b	458 ± 36^bc	949 ± 64^bcd	841 ± 61^bcde	899 ± 35^bcdef
IL-10	乌司他丁组	15	11.7 ± 0.9^a	31.9 ± 2.6^ab	54.7 ± 4.8^abc	80.7 ±1.9^abcd	69.4 ± 3.4^abcde	74.3 ± 5.5^abcdef
?	对照组	15	5.7 ± 0.8	17.2 ± 1.6^b	22.3 ± 2.1^bc	42.3 ± 4.9^bcd	29.7 ± 1.4^bcde	21.4 ± 2.9^bcdef

指标	组别	只数	0.5 h	2h	4 h	12 h	24 h	72 h
TNF-α	乌司他丁组	15	14.8 ± 2.5^a	48.8 ± 3.9^ab	56.3 ± 4.2^abc	106.4 ± 65.8^abcd	119.8 ± 28.9^abcde	112.3 ± 10.2^abcdef
?	对照组	15	21.6 ± 3.8	69.2 ± 3.2^b	74.8 ± 6.9^bc	120.2 ± 43.8^bcd	190.2 ± 30.4^bcde	159.7 ± 10.5^bcdef
IL-6	乌司他丁组	15	119 ± 5^a	225 ± 22^ab	273 ± 28^abc	328 ± 27^abcd	306 ± 6^abcde	278 ± 16^abcdef
?	对照组	15	145 ± 6	344 ± 19^b	458 ± 36^bc	949 ± 64^bcd	841 ± 61^bcde	899 ± 35^bcdef
IL-10	乌司他丁组	15	11.7 ± 0.9^a	31.9 ± 2.6^ab	54.7 ± 4.8^abc	80.7 ±1.9^abcd	69.4 ± 3.4^abcde	74.3 ± 5.5^abcdef
?	对照组	15	5.7 ± 0.8	17.2 ± 1.6^b	22.3 ± 2.1^bc	42.3 ± 4.9^bcd	29.7 ± 1.4^bcde	21.4 ± 2.9^bcdef

组别	只数	0.5 h	2h	4 h	12 h	24 h	72 h
乌司他丁组	15	290 ± 17^a	336 ± 9^ab	492 ± 14^abc	608 ± 17^abcd	579 ± 16^abcde	505 ± 9^abcdef
对照组	15	320 ± 8	400 ± 7^b	536 ± 10^bc	806 ± 10^bcd	781 ± 17^bcde	662 ± 24^bcdef

组别	只数	0.5 h	2h	4 h	12 h	24 h	72 h
乌司他丁组	15	290 ± 17^a	336 ± 9^ab	492 ± 14^abc	608 ± 17^abcd	579 ± 16^abcde	505 ± 9^abcdef
对照组	15	320 ± 8	400 ± 7^b	536 ± 10^bc	806 ± 10^bcd	781 ± 17^bcde	662 ± 24^bcdef

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