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The Study of Relationship between Hepatic Sympathetic Regulation and Acute Liver Injury

Author: ZengYi
Tutor: WangShuGuang
School: Third Military Medical University
Course: Surgery
Keywords: Liver injury Sympathetic denervation Norepinephrine Carbon tetrachloride Neurophysiological Tumor Necrosis Factor Kupffer cells TNF-a and IL-1βmRNA Endotoxin
CLC: R363
Type: Master's thesis
Year: 2010
Downloads: 36
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Abstract

, Background in clinical cause of acute liver injury due to severe trauma, major surgery of the liver, poisoning, bacteria, virus infection leading to acute liver failure. Induced acute liver injury, liver function insufficiency or acute liver failure, clinical treatment is very tricky, drug Baogan difficult to receive the desired effect. In this pathological process, due to trauma, such as bacteria, viruses, a direct result of liver cell damage is limited, while the body itself for some minor damage or pathogens inappropriate inflammatory or immune response may result in serious consequences. Too strong inflammatory response to the large number of inflammatory mediators into the bloodstream can cause systemic inflammatory response syndrome (systemic inflammatory response syndrome, SIRS) caused shock and multi-system organ failure (multi-system/organ failure MSOF), acute liver The injury is a systemic inflammatory response syndrome an organ performance. Inflammation and development is a complex process, subject to a number of factors and adjust. Involved in the regulation of the body's inflammatory response factors can be broadly divided into two major categories of body fluids and nerve mononuclear macrophages play a crucial role in inflammation. Mainly concentrated in the inflammatory response and liver injury in humoral regulation, due to the lack of a good animal model for the study of the neural regulation, less research data shows. The the hepatic sympathetic regulation system consists of the celiac ganglion, spinal thoracolumbar hypothalamic central sympathetic three different levels of the central constitute. Kupffer cells in the liver is a principal member of the monocyte-macrophage cell system is macrophage residence in the liver, accounting for the systemic macrophage total number of more than 80%, 35% of the total number of liver parenchymal cells, play an important defense function. Kupffer cell activation and the liver acute and chronic inflammation is closely related. Comprehensive research results at home and abroad in recent years, we infer the occurrence of acute liver injury and development, with the sympathetic activity changes at all levels of the central sympathetic nervous system is entirely possible regulation of neurotransmitter release directly regulated by Kupffer cells expression of inflammation-related factors, involved in the start-up and trigger excessive inflammatory response. Second, the aim of the present study was to be sympathetic treatment from different segments of the control system of the liver sympathetic to explore the performance of various segments of the sympathetic nervous system in the regulation of acute liver injury, and validated by in vitro experiments of sympathetic activation in acute liver injury development regulation effect. From a new perspective, new understanding of the systemic inflammatory response and the adjustment mechanism of the corresponding organ damage, and provides a new way of thinking for the treatment of excessive inflammatory response (SIRS) and MODS. Third, the method and the results of a different segment sympathetic denervation on CCL4 induced acute liver injury: blocking the sympathetic nerve conduction from the cervical sympathetic trunk and splanchnic nerve, and the nerve endings in the liver of different regulation section segment path CCL4 application based on acute liver injury model. Issuance frequency and amplitude changes with the recording electrodes determination sympathetic impulses, liver function, serum TNF-a concentration, and liver histopathology, high-performance liquid chromatographic method for the determination of the relevant indicators of liver tissue of NE. (1) lower volatility of normal rat cervical sympathetic dry discharge frequency uniform, voltage stabilized later by the CCL4 intraperitoneal injection of liver injury stimulation, sympathetic trunk discharge immediately increase wave V increases, was pulsed enhancements, continued record about 40 seconds later, the sympathetic nervous electrical activity returned to normal when the waveform. ② cervical sympathetic trunk away from the segment, intrahepatic sympathectomy group were compared and shame group: albumin and prealbumin increased significantly reduced, AST, ALT, total bilirubin, and the liver function indicators, the difference was significant (P lt ; 0.05, P lt; 0.01). Splanchnic nerve from the off and shame group the liver function indexes were significantly (P gt; 0.05). ③ cervical sympathetic trunk go off group and intrahepatic sympathetic with the shame group compared liver tissue norepinephrine concentrations significantly lower, the difference was significant (P lt; 0.01). Splanchnic nerve transection and shame group no significant changes, results of statistical differences (P gt; 0.05). ④ neck sympathetic trunk transection, the intrahepatic go sympathetic serum TNF-a levels (P lt; 0.05), splanchnic nerve transection group compared to the shame group increased significantly reduced compared to shame. Isolated and purified, sympathetic neurotransmitter NE endotoxin-induced rats kupffer cell TNF-a / IL-1β expression in situ perfusion IV collagenase digestion and percoll were expanded for density gradient centrifugation and selective adherence kupffer cells were divided into three groups of culture. Group A (the control group); B group (LPS); C group (LPS NE) Real time PCR and ELISA, KC, TNF-α, IL-1βmRNA expression and protein level. ① KC normal cell under almost no expression of TNF-a and IL-1β, to exogenous endotoxin LPS (final concentration 10μg/ml) stimulation, in 12 hours TNF-a, IL-1βmRNA expression was significantly increased; while comparison, TNF-a mRNA level added to a final concentration of norepinephrine 1μmol / L and 10μmol / L of culture medium treated with LPS group were increased by 50.9% (P lt; 0.05) and 59.1% (P lt; 0.05 ), the IL-1βmRNA level than LPS group increased 53.7% (P lt; 0.05) and 57.8% (P lt; 0.05), its expression levels and norepinephrine epinephrine concentration was positively correlated; ② The of TNF-a, IL-1β at the protein level The results are consistent and mRNA levels. Under normal circumstances, almost no expression or trace expression, LPS (10μg/ml) expression was significantly higher after stimulation. Costimulatory (LPS NE), TNF-a, IL-1β concentration of norepinephrine concentration 1μmol / L and 10μmol / L compared with LPS group was significantly increased (P lt; 0.05) at low concentrations (0.1μmol / L), the result was no significant difference. Conclusion: 1, the sympathetic regulatory system different segments sympathetic denervation can significantly reduce CCL4 liver dysfunction due to acute liver injury, liver tissue decreases norepinephrine levels. Various segments of the sympathetic nervous system is relatively independent regulatory functions to maintain the stability of the body function to regulate Also may be antagonistic due to sympathetic afferent pathway damage vagus nerve center of the reflex enhancement. 2 different segments of the sympathetic regulation activation promote inflammation effect in acute liver injury in the early course of the disease. Sympathetic activation may be through a direct role kupffer cells and promote the expression of inflammatory cytokines in a certain concentration range, with the increase in norepinephrine concentrations increase in the expression of pro-inflammatory cytokines.

The Study of Relationship between Hepatic Sympathetic Regulation and Acute Liver Injury

Abstract

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