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| The effects of terlipressin combined with norepinephrine on acute liver injury in rats with septic shock |
| Zhao Guang-ming, Guo Hai-yang, Zhong Lei, Wang Yan-lin, Liu Zhi-han, Hu Zhan-sheng |
| The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China |
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Abstract Objective To investigate the effects of terlipressin (TP) combined with norepinephrine (NE) in rats with acute liver injury induced by septic shock and its mechanisms. Methods Forty-eight male Sprague-Dawley rats were randomly divided into four groups (n=12 each), control group (Control), model group (LPS), norepinephrine group (NE), terlipressin + norepinephrine group (TP+NE). LPS, NE and TP+NE groups were injected slowly with lipopolysaccharide (LPS) 5 mg/kg and normal saline (NS) with a total of 0.5 ml via right internal jugular vein for 5 min. Mean arterial pressure (MAP) dropped by >40 mm Hg over the course of 30 min, that replication of septic shock model was successful. While Control group was injected slowly with NS 0.5 ml via right internal jugular vein for 5 min. Fluid resuscitation with NS (5 ml/kg/h) in NE and TP + NE groups, while NE and TP+NE were added respectively until the MAP returned to basal level and maintained 1 h for the resuscitation compliance. For Control and LPS groups, no fluids or drugs were administered. Hemodynamics, tissue perfusion and oxygen metabolism indices were recorded and the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum were detected by ELISA. Furthermore, 4 ml of right internal jugular vein blood samples were taken, and the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations were measured by ELISA. After the end of the experiment, the rats were killed and liver tissue was taken, and the activity of total superoxide dismutase (T-SOD) and the content of malondialdehyde (MDA) in liver tissue were measured by colorimetry. The pathological changes of liver tissue were observed by light microscope. Results Compared with Control group, the concentrations of AST and ALT in serum, the levels of IL-6 and TNF-α in serum increased in LPS group (P<0.05). The histopathology examination was performed, and abnormal structure, inflammatory cell infiltration, liver cell necrosis could be found in the tissue. This indicated that the animal model of the acute liver injury induced by septic shock was successfully prepared. Compared with LPS group, the concentrations of AST and ALT in serum, the content of MDA in liver tissue and the levels of IL-6 and TNF-α in serum decreased (P<0.05), the activity of T-SOD in liver tissue increased in NE and TP + NE groups (P<0.05), and pathological damage to the liver tissue has been alleviated to varying degrees. Compared with NE group, the concentrations of AST and ALT in serum, the content of MDA in liver tissue, the levels of IL-6 and TNF-α in serum decreased (P<0.05), the activity of T-SOD in liver tissue increased (P<0.05) and pathological damage to the liver tissue alleviated dramatically in TP + NE group. Conclusion In the treatment of septic shock, based on adequate fluid resuscitation, continuous venous pumping of low dose TP combined with lower dose NE can protect acute liver injury in rats induced by septic shock, and the mechanisms of action may be mediated by stabilizing hemodynamics, improving liver perfusion, reducing the levels of blood lactate and intrahepatic oxygen free radicals, reducing the production of inflammatory cytokines IL-6 and TNF-α in serum, and reducing liver damage, thereby protecting liver function in rats with septic shock.
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Corresponding Authors:
Hu Zhan-sheng, E-mail: ICUHZS@163.com
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