Clinical Expirical Study Of Intensive Insulintherapy In Severe Trauma

Background: Severe posttraumatic stress hyperglycemia will lead toincreased mortality and poor prognosis in patients with trauma. Research showsthat TNF-α and IL-6, as proinflammatory cytokines, were produced in severetrauma patients. The cytokines aggravated endothelial system and liver tissuedamage, ultimately leading to coagulation function disorder and increasedmortality, which may be associated with nuclear transcription factor NF-κB, butits exact mechanism is still not clear.At present, there is no uniform understanding if low mortality in patientstreated with intensive insulin therapy can be related to inhibit high inflammatorystate, reduce the NF kappa B levels and protect endothelial and liver function.Therefore, our research will be very important for clinical therapy. This paper isdivided into two parts. The first part is clinical trials about the effect of intensiveinsulin therapy on inflammatory mediators, endothelin system and coagulationfunction in patients with severe trauma. The second part is basis trials about theliver injury protection mechanism of intensive insulin therapy on hyperglycemiain a rat model.Objective: To explore the effects of intensive insulin therapy on theinflammatory mediators, peripheral blood nuclear transcription factor effects insevere trauma patients with stress hyperglycemia; to explore the effects ofintensive insulin therapy on endothelin system and coagulation function in severetrauma patients with stress hyperglycemia; to study the protective function ofintensive insulin treatment on the liver injury in animal level.Methods:In the first part, TNF-α, IL-6and NF-κB activity were detected byELISA and PCR. VEGF,ET-1,CRP and CEC counting were measured by ELISARadioimmunoassay and percoll density gradients in one step; PC, PS, TM, t-PA and PAI-1contens were detected by ELISA, Antithrombin III (AT (III) activitywas detected by chromogenic substrate method. In the second part, ALT, AST, TBi,ALB, TP and ALP were detected by full automatic biochemical analyzer. Livertissue were observed by HE staining and transmission electron microscope.NF-κB expression was showed by Immunohistochemistry, Phosphorylatied IκBwas conducted by Western Blotting.Results: In the clinical experimental study, time in antibiotic use, in ICU andaverage days in hospital were shorten; nosocomial infection and multiple organfailure rate were reduced; TNF-α and IL-6in the serum levels, VEGF, ET-1, CRPand peripheral blood CEC counting were decreased; the intensive insulin therapycan significantly decrease the NF kappa B expression. APTT, PT and TT wereshorten; FBG,PC and PS were increased; TM, PAI-1and DD were decreased.Hyperglycemia liver injury rat model was established firstly. Intensive insulintherapy can decrease the rat hepatic function index, increase albumin and totalprotein content; pathology and transmission electron microscopy results showedthat liver cell injury can be decreased effectively, liver cells regeneration werepromoted; immunohistochemistry data found that NF kappa B expression in livercells was significantly reduced; intracellular phosphorylated IκB expression inliver cells was reduced, effectively protecting liver function.Conclusion: Intensive insulin therapy can effectively lower the post-traumaticinflammatory mediators levels and reduce the NF kappa B transcription level;Intensive insulin therapy can protect the endothelium injury after trauma;intensive insulin therapy can effectively improve the severe trauma in coagulationsystem disorders; intensive insulin therapy can significantly reduce liver functionin hepatic injury model rat with hyperglycemia, effectively protect the hepaticcells.