| ObjectiveThe current study still utilized severely scalded and immunosuppressive rats model on the basis of our previous studies, which can lead to gut injury and gut original infection, simulating the pathophysiologic changes developed form clinical serious postburn patients with immunologic hypofunction , was performed to explore the apoptotic tendency of intestinal epithelial cells; to investigate whether recombinant human growth hormone (rhGH) can improve intestinal mucosal barrier in severely scalded rats and by which possible mechanisms these changes occur; and the effect of combined administration of rhGH and meropenem on the enterogenic infection and prognosis in severely scalded rats.Methods172 grown male Wistar rats were randomly divided into five groups, i.e. control, scald, GH, meropenem, and GH + meropenem groups. The latter four groups were inflicted with 25% total body surface area full-thickness skin scald on the back and immediately followed by intraperitoneal injection of dexamethasone (80 mg/kg) and by abdominal hypodermic injection of normal saline(50mL/kg) to antishock. The scaled rats in the four groups were subcutaneously injected with normal saline, rhGH [ 1.33 IU / ( kg·d ) ], meropenem (20mg/kg) and rhGH [1.33 IU/(kg·d) ] + meropenem (20mg/kg) respectively from 2 hours to 3 days after scald.(1) 36 grown male Wistar rats were randomly divided into control and scald groups. The changes of apoptosis of intestinal epithelial cells were detected by flow cytometry, HE stain, TUNEL and fluorescence method on 6h, 12h, 1d, 3d, 5d after burn.(2) 42 grown male Wistar rats were randomly divided into control, scald and GH groups. The effect of early use of recombinant human growth hormone on apoptosis of intestinal epithelial cells was detected by HE stain, TUNEL and fluorescence method on 12h, 1d, 3d after burn.(3) 94 grown male Wistar rats were randomly divided into control, scald, GH, meropenem, and GH + meropenem groups. The effect of early use of recombinant human growth hormone and meropenem on the enterogenic infection and prognosis in severely scalded rats was observed by MLN bacteriology test, HE stain, changes of weight and survival rate.Results(1) Flow cytometry analysis, HE stains, TUNEL and fluorescence test showed that significantly increased apoptotic intestinal epithelial cells were found in scaled group rats and reached the peak on 1d and decreased thereafter. But it was still stronger than control group(P<0.01).(2) The intestinal mucosal histomorphology and intestinal epithelia in scald group was severely injured but significantly meliorated by rhGH to near that in control group. The intestinal mucosal cellular apoptosis rate in both scald and GH groups was significantly higher than that in control group(P<0.01) while that in GH group was evidently lower than that in scald group (P<0.01), and reached the peak (15.40%±3.21% vs 38.80%±6.98%) at 24h after burn. Also, the activity of Caspase-3 was significantly increased in scald and GH groups than in control group(P<0.05) while it was lower in GH group than scald group(P<0.05), and reached the peak (156.13±4.66 U/mg vs 214.60±9.29 U/mg) at 24h.(3) In the GH + meropenem group, we had not find bacteria in MLN, nor abscess in organs. The weight descent in this group was markedly lower than other groups (P<0.05). The pathohistological constructions were near the normal rats. There was not any rat death postburn 10 days.Conclusions(1) The apoptosis rate of intestinal epithelial cells increased after severe burn, particularly at 1d postburn.(2) rhGH administered in early severe burn could inhibit the intestinal mucosal cellular apoptosis, and which might be induced by the down regulation of the activity of Caspase-3 due to the effect of rhGH. As a result, the intestinal mucosal damage after severe burn could be meliorated by rhGH mainly by means of its inhibiting roles and intestinal mucosal integrity and function was maintained ad hoc.(3) Combined administration of rhGH and meropenem could effectively control gut original infection and decrease mortality. |
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