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| The cardiac protective effects of Ulinastatin in different dose for sepsis-induced myocardial dysfunction mice |
| Chen Yu-hong, Zhang Kun, Hu Zhen-jie |
| Intensive Care Unit, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China |
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Abstract Objective To evaluate the protective mechanism and efficacy of ulinastatin in different dose for sepsis-induced myocardial dysfunction (SIMD) rats. Methods Thirty-two Kunming (KM) mice were randomly divided into 4 groups (n=8): Control group, SIMD group, SIMD+low dose UTI (LU) group and SIMD + high dose UTI (HU) group.LVEF and LVFS were obtained by transthoracic two-dimensional M-mode echocardiography, then we sacrifice the mice and collected their bloods and hearts. The heart histological change was observed by HE, the levels of plasma cTnI, CK, TNF-α, IL-1β were detected by ELISA. The expression of TLR4 in heart tissue was measured by western blot. Results LVEF and LVFS were significantly decreased in SIMD mice compared with the control group［LVEF (%):49.38±6.97 vs. 80.63±5.13, LVFS (%): 25.13±5.44 vs. 49.25±〖JP〗4.27, respectively，P＜0.01］, but the plasma levels of cTnI, CK, TNF-α, IL-1β as well as the protein levels of TLR4 were significantly increased［cTnI (ng/mL):3.66±0.61 vs. 2.75±0.33, CK (U/L):3480.70±714.05 vs. 1485.19±444.28, TNF-α (μg/L): 185.57±43.73 vs. 42.15±19.06, IL-1β (μg/L): 61.63±21.36 vs. 31.57±5.49, TLR4: 0.94±0.13 vs. 0.61±0.12, respectively，P＜0.01］. HU-treated mice showed an increase in LVEF and LVFS(68.13±5.22 vs. 49.38±6.97, 37.38±4.21 vs. 25.13±5.44, respectively,P＜0.01), and an decrease in the plasma levels of cTnI, CK, TNF-α and IL-1β(2.91±0.39 vs. 3.66±0.61, 2309.91±575.94 vs.3480.70±714.05,124.73±27.18 vs. 185.57±43.73, 40.78±12.09 vs. 61.63±21.36, respectively, P<0.01). In addition, the protein level of TLR4 was decrease compared with SIMD group (0.71±0.14 vs. 0.94±0.13, P＜0.01). Administration of LU could improve the cardiac damage and attenuate LPS induced inflammation, but without statistical difference.Histomorphological changes of heart: In control group, the structure of heart tissue was essential normal. In SIMD group, we can observed some changes in myocardial fiber rupture, interstitial edema, enlarged intercellular space, inflammatory cell infiltration, etc.Compared with SIMD group, histomorphological changes of SIMD+HU group was improved. Conclusion High dose of Ulinastatin could decrease the expression of TLR4 levels in heart, and inhibit release of downstream inflammatory factors, which possesses the protective effects on the heart in septic mice, however, the addition of low dose Ulinastatin is not obvious.
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Corresponding Authors:
Hu Zhen-jie, E-mail: syicu@vip.sina.com
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