Study The Influence Of Insulin On The Live NF-κB Inflammation Pathway Activated By Endotoxin Or Chemerin

Objective:To study the relationship of serum insulin level with inflammation, glucose, lipid metabolism and liver function of bacterial liver abscess on clinical level, and study the anti-inflammation mechanism of insulin on the hepatocyte after LPS or chemerin challenge on cell level, it is aimed to provid a primary theoretical basis for the clinical application on insulin treatment for serious infection.Methods:1.198bacterial liver abscess cases were selected and divided as fatty liver group (group A) and non-fatty liver group (group B). Then. Group A and group B was divided respectively into group A1and group B1(not with type2diabetes), and group A2. group B2(with type2diabetes). At the same time, according to insulin levels, patiens were divided into four groups (group1<group2<group3<group4). Parameters were detected including Fins. HbA1c, blood glucose, blood lipids, liver function. ESR. LPS, CRP, calculated HOMA-IR. people constituent ratio and liver/spleen CT value ratio. At last, relationship between insulin levels, sugar lipid metabolism indexs and inflammation indexs was analyzed.2. HepG2cell was cultivated in vitro and observed under inverted microscope. Cultivated cells were divided into sixteen groups:(1)normal control group,(2)LPS damage group,(3)LPS+2.5IU/ml insulin group.(4)LPS+5IU/ml insulin group.(5)LPS+10IU/ml insulin group,(6)chemerin group,(7)chemerin+2.5IU/ml insulin group,(8)chemerin+5IU/ml insulin group.(9)chemerin+10IU/ml insulin group.(10)LPS+chemerin group,(11)LPS+chemerin+2.5IU/ml insulin group.(12)LPS+chemerin+5IU/ml insulin group,(13)LPS+chemerin+10IU/ml insulin group,(14)2.5IU/ml insulin group.(15)5IU/ml insulin group,(16)10IU/ml insulin group, and give them intervention respectively in6h.12h.24h. ELISA was introduced to measure TNF-α, IL-6, NF-κB. IκBα; TLR-4was determined by flow cytometer.Results:1.The constituent ratio of group A and group B was27.92%and72.08%. group A1:19cases (9.6%). group A2:36cases (18.27%), group B1:58cases (28.93%). group B:2:85cases (43.15%). For four groups divided according to insulin levels, level of ESR. CRP and endotoxin among groups were respectively (69.96±12.59vs46.87±12.40vs43.67±12.22vs44.90±7.98)mm/h,(92.68±22.47vs84.40± 22.64vs50.64±16.93vs6130±19.83)pg/ml,(6.91±1.28vs8.08=1.52vs2.86±1.52vs3.62=1.52)pg/ml. The correlation analysis results showed that insulin was negatively correlated with level endotoxin, CRP, ESR, liver/spleen CT ratio and AST. multiple regression analysis results showed that liver/spleen CT value. ESR. CRP was the risk factors of insulin.2. The HepG2cells were well subcultured. NF-κB and IL-6was increased significantly comparing with normal control group and insulin control group after intervention of LPS.chemerin.and LPS combination chemerin, and becomed higher in level with time extended; On the contrary.IκBα decreased significantly and becomed lower with time extended;TNF-a remained same. After inverted by different concentrations of insulin. NF-κB and IL-6decreased when the insulin concentrations increased, in contrast the IκBα increased when insulin concentrations increased; and TNF-a still remained unchanged; Compared with normal control group and the insulin control groups, there were no significant differences in NF-κB. IκBα, IL-6. TNF-α. In conclusion, LPS, chemerin enhanced the TLR-4expression, on the contrary insulin downregulated the TLR-4expression.Conclusion:1. In the present study, we found that in bacterial liver abscess patients, about43.15%were complicated with type2diabetes, and about9.6%with simple fatty liver. It was considered to be due to the IR in nonalcoholic fatty liver disease caused by high insulin hematic disease, and low insulin hematic disease in type2diabetes caused by islet function impairment. For insulin-levels-divided bacterial liver abscess patients.serum level of CRP, ESR, endotoxin, ALT, AST level reduced with increased insulin level, and albumin level increased with increased insulin level, We hereby assumpted that insulin would improve liver function and inflammatory condition.2.LPS. chemerin can activate the NF-κB signal transduction pathway producing inflammation by increasing TLR-4expression. Insulin could down regulation of TLR-4expression and inhibit NF-κB signal transduction pathway, at last the production of inflammatory factor bacterial liver abscess patients and play anti-inflammatory effects by a concentration dependencing way.