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| Effects of U50488H on cytokines in septic shock rats |
| Wang Qian-mei, Fan Yuan-yuan, Zhao Peng, Wang Wei, Huang Yang, Yin Wen |
| Department of Emergency Medicine, Xijing Hospital, Air Force Military Medical University, Xi′an 710032, China |
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Abstract Objective To investigate the effects of U50488H on cytokines in septic shock rats and explore its protective mechanisms. Methods Forty male Sprague-Dawley rats were randomly divided into four groups (n=8): sham group, septic shock group, U50488H+septic shock group, nor-BNI+U50488H+septic shock group and nor-BNI+septic shock group, with 8 rats in each group. In sham group, only open-close abdomen was performed. Cecal ligation and puncture (CLP) was performed to induce septic shock in septic shock group. Rats of U50488H+septic shock group were treated with U50488H injection intravenously at the shock point, and other procedures were the same as the septic shock group. Rats of nor-BNI+U50488H+septic shock group were treated with nor-BNI injection intravenously 3.5 h after abdomen closed, and other procedures were the same as U50488H+septic shock group. Except for U50488H injection, the rats of the nor-BNI+septic shock group received procedures the same as nor-BNI+U50488H+septic shock group. Central vena cava oxygen saturation (ScvO2), lactate (Lac), proportion of peripheral neutrophilic granulocyte, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), vascular cell adhesion molecule (VCAM), lactate dehydrogenase (LDH) and superoxide dismutase (SOD) in serum were measured at abdomen-closed, 3, 6, 12 hours after CLP. Another 30 rats were randomly divided into three groups (n=10): sham group, septic shock group, U50488H+septic shock group. And the survivals of 24 h were evaluated. Results After 3, 6, 12 hours of CLP, the ScvO2, IL-10 and SOD in serum of the septic shock group were lower than that of the control group (P<0.01), while the proportion of peripheral neutrophilic granulocyte, Lac, TNF-α, IL-1β, IL-6, VCAM and LDH were higher (P<0.01). The differences of ScvO2 in the septic shock group and U50488H+septic shock group were not statistically significant. Compared with septic shock group, the levels of the proportion of peripheral neutrophilic granulocyte, Lac, TNF-α, IL-1β, IL-6, VCAM and LDH of the U50488H+septic shock group decreased (P<0.01, P<0.05), whereas the levels of IL-10 and SOD in serum increased significantly (P<0.01). Moreover, the above effects of U50488H were pretreatment abolished by nor-BNI (a selective κ-opioid receptor antagonist) (P<0.01). The survival rate of 24 h in U50488H+septic shock group was higher than that of septic shock group (P<0.05). Conclusion U50488H has protective effects on rats with septic shock by improving tissue perfusion, inhibiting inflammation, reducing tissue damage, enhancing the anti-oxidation capacity, and can lower the mortality rate.
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Corresponding Authors:
Yin Wen, E-mail: xjyyyw@fmmu.edu.cn
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