| ObjectiveBy investigate the influence of early application recombinant human growth hormone (rhGH) on gut derived sepsis and prognosis in severely scalded rats, to evaluate the clinical effect of application the human growth hormone on the severely burn patients in shock stage.MethodsThis topic studies including two parts: the animal experimental research and the clinical practice. The animal experimental studies: 54 male Wistar rats were randomly divided into three groups: the control group, the burn group and the GH group. The rats in scalding and GH groups were inflicted with 25% TBSA III degree scalding on the back and immediately followed by intraperitoneal injection of dexamethasone (80 mg/kg). The scalded rats were administered with normal saline and rhGH(l. 331U·kg-1·d-1) at 2 postburn hours(PBHs), respectively in the last two groups. The changes of abcess in liver, spleen, kidneys, lungs, portal and cava venous, the viable bacterial counts in tissues, the patholigical and functional changes of main organs were obsevered in 4,7,10 postburn days(PBDs). The changes of weight and survivor rate were determined. The changes of the serum endotoxin levels and tumor necrosis factor-α(TNF-α). Clinical practice research: 77 severe burn patients were randomly divided into three groups: control, GH1 and GH2 groups. GH1 group was treated with rhGH within 24h after burn and GH2 group treated 5 days after burn , to observe of incidence and mortality rate of sepsis and MODS, and wounds healing, hospitalized time, and the blood sugar change in 3 groups.ResultsAnimal experimentation part:1. visual observation:4, 7 and 10 PBDs after burns, compares with the control group, the burn group animal intestines wall and the intestines mucous membrane were obviously thin, and intestines mucous membrane has ulcer, hemorrhage tendency; The mesentery lymph node (MLN) were enlarged in varying degree; The visceral organ has the suppuration stove number to increase. The incident of abscess was 41.7%, 58.3% and 64.6% respectively, The suppuration focus by small gradually is big, The density by becomes sparsely fills the air;The abdominal wall fat reduces obviously along with the time lapse, the abdominal wall changes thin. But in the GH group animal 4 PBDs, compares the control group the intestines wall and the intestines mucous membrane were obviously thick, 7 and 10 PBDs was similar to control group, has no obvious intestines mucous membrane ulcer and the hemorrhage; Mesentery lymph node (MLN) tumescent degree obvious lightly; The abdominal wall is thick, the abdominal cavity internal organs are plentiful.2. The change of breath, body weight and survival rate7 PBDs, the changes of respiratory rate(p<0.01) and weight loss(p<0.05) in GH group were both lower than those in scalded group. The 10 days survivor rate in GH group(9/12) was higher than that in scalded group(5/12).3. Bacterial10 PBDs, 7 kind of bacteria were count in two groups from MLN, liver, spleen, kidney, lung and portal and cava venous: E coli, the clavate bacillus, the enterococcus, the pseudomonas aeruginosa, the gram Reber bacillus, the bacillus proteus Portugal ceramic coccus. The MLN , lung and liver is highest. The level of bacterial count in GH group was significantly lower than that in scalded group(p<0.01).4. pathological changes10 PBDs, ileum: The burn group intestines wall changes thin, the intestines mucous membrane and the down obvious atrophy, mucous membrane ulcer and hemorrhage. The GH group intestines wall is thick, intestines mucous membrane and down shape structure were similar to control group. Liver: The burn group liver partial hepatic lobe disarrangement in structure, and the suppurative infection focus. GH group hepatic lobe structure was basic normal, little lymphocyte infiltration. Spleen: red, white marrow structure basic normal in two groups. Kidney: The burn group kidney has local suppurative focus ., partial renal glomeruli destroy or lack; The approaching tubulus renalis atrophy, the tubulus renalis epithelial cell assumes partial denaturation. GH group kidney structure basic normal, the renal glomerulus is mild proliferation. Lung: The burn group lung has the suppurative focus, consolidation, hemorrhage and focus necrosis, around the focus the pulmonary alveolus were expand or to atrophy. The GH group lung pulmonary alveolus capillary mild expansion and the hemorrhage.5. The changes of the blood serum endotoxin levels and tumor necrosis factor-α(TNF-α) .The levels of blood serum endotoxin levels and tumor necrosis factor-α(TNF-α) in burn and GH group are obviously higher than the control group (P<0.01), and also the levels in GH group are obviously lower than burn group.6. Changes of blood serum in venae cavae liver, kidney10 PBDs, burn group animal blood serum ALT and Cr obviously are higher than the control group (P<0.01). GH group to be lower than the burn group obviously (P<0.01～0.05), compare with control group has no statistics significance. Although two group of AST and BUN obviously are higher than the control group (P<0.01), but the GH group obviously is lower than the burn group actually (P<0.01～0.05).Clinical practice part1. sepsis incidence The GH 1 group of sepsis incidence is18. 52%(P<0.01),whthin 5ds the incidence is only 11.11%(P<0.05), It Not only is lower than the control group obviously, also is lower than the GH2 groups; GH2 group although compares the control group reduces, but two group has no statistics significance.2. MODS incidence and mortalityThe incidence of MODS in GH1 group is only 3.70%, the mortality rate is 0, 1 patient with burn area 98%TBSA and third degree burn 93% is also cure; MODS incidence and mortality in GH1 group are Not only lower than the control group, also is lower than the GH2 groups (3.70% vs 13.79% vs 19.05%,Ovs 6.90% vs 9.52%), But has no statistics significance (P>0.05).3. Blood sugar changesThe blood sugar levels in GH1 and GH2 groups were higher than in control group (P<0.01)whthin 14d of using rhGH, but there is no statistics significance (P>0. 05) between the two groups before and after using rhGH.Conclusion1. The intestinal tracts as the biggest bacterial and endotoxin storehouse, play an important role in concealment infection sources. The bacterium migrate out from intestinal tract to MLN and other parts then cause body-wide infection is an progressive process. In this process, shifting bacterium and endotoxin and the inflammatory medium may cause damage of tissues. along with the time passage, the pathological change will act progressively according to the bacterium, the toxin and the inflammatory medium toxicity or (and) the host immunity change, the inflammation may be control, or develop to partial suppuration, or transfers the chronic inflammation, or the inflammation proliferation forms the intestines source sepsis, the septic shock and (MODS) and even death.This research uses the burn immunosuppression animal model, 4, 7, 10 PBDs, incidence of the animal internal organs abscess in burn group is 41. 7%, 58. 3% and 64.6% respectively; 7, 10 PBDs animal intestines, liver, spleen, kidney, lung and other internal organs present pathology changes in varying degree: the organs atrophy, the tissue structure destroys, anxious or chronic inflammation coexisting, the function of intestines, liver, kidney and lung obviously abnormal. 10 PBDs the mortality rate reaches 58.3%(7/12). These show this animal model has good reflection to the development and the evolution process of gut derived sepsis in severe burn.2. rhGH possibly has function in protection of intestines mucous membrane barrier, the immunity function regulation, the nutrition condition improvement and protection of tissue and organ in many ways. This experimental study indicated that in the GH group the animal internal organs abscess incidence, the internal organs and MLN and the blood bacterium account rate obviously reduce at 4, 7, 10 PBDs compares the burn group, and 10 PBDs survival percentage distinct higher. The result show that in severe burn early time stage application large dose rhGH, can reduce the gut derived sepsis, can reduce the tissue damage, enhances the animal survival rate.3. This study indicated that, after the serious burn 24h starts to apply rhGH, the total and 5 PBDs sepsis incidence rate, MODS incidence rate and mortality rate, not only is obviously lower than that has not applied rhGH group, also is obviously lower than that 5 PBDs to start to apply the rhGH group. This show that in shock shock stage of severe burned patients start to use rhGH, can reduce sepsis and MODS incidence rate obviously, enhances the survival rate. These effects are mainly by reduces the early sepsis incidence rate. So early using rhGH can promote wounds healing, reduces in hospital time, but should monitor the blood sugar change strictly.
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