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γ-羟基丁酸对大面积热损伤大鼠模型中高代谢及伤口愈合的影响

The effects of gammahydroxybutyrate on hypermetabolism and wound healing in a rat model of large thermal injury.

作者信息

Murphy Kevin D, Rose Mary W, Chinkes David L, Meyer Walter J, Herndon David N, Hawkins Hal K, Sanford Arthur P

机构信息

Northern Ireland Plastic and Maxillofacial Service, The Ulster Hospital, Dundonald, Belfast, Ireland.

出版信息

J Trauma. 2007 Nov;63(5):1099-107. doi: 10.1097/TA.0b013e318157d9d0.

Abstract

BACKGROUND

Growth hormone (GH) improves wound healing and ameliorates pediatric postburn tissue catabolism associated with deficient endogenous GH/IGF-1 levels. Expense, parenteral administration, and compliance have limited widespread usage. Gammahydroxybutyrate (GHB), an upstream neuromodulatory gamma-amino butyric acid (GABA) derivative, is known to increase slow wave sleep and stimulate endogenous GH secretion. In this study, improvement in GH levels in turn has been shown to accelerate wound healing.

METHODS

Body composition in male Sprague-Dawley rats with > or =40% total body surface area scald burn, receiving incremental GHB doses orally, was assessed by Dual Energy X-Ray Absorptiometry. Serum GH and IGF-1 levels were measured. Wound cross sections were scored semiquantitatively for wound healing variables.

RESULTS

Incremental elevation in GH and IGF-1 were associated with significantly improved wound edge epithelialization and cell-layer thickness at high doses (p < 0.005). However, body composition was similar to that of burned controls.

CONCLUSIONS

GHB sufficiently elevated serum GH and IGF-1 levels to significantly improve epithelialization rates and layer thickness at high doses. Substantially greater elevations of serum GH and IGF-1 levels are required in the rat burn model than for humans. GHB may improve postburn hypermetabolism in humans by elevating endogenous GH levels, though only improved epithelialization was demonstrated in this study.

摘要

背景

生长激素(GH)可促进伤口愈合,并改善与内源性GH/IGF-1水平不足相关的小儿烧伤后组织分解代谢。费用、胃肠外给药及依从性限制了其广泛应用。γ-羟基丁酸(GHB)是一种上游神经调节性γ-氨基丁酸(GABA)衍生物,已知可增加慢波睡眠并刺激内源性GH分泌。在本研究中,已证明GH水平的改善进而可加速伤口愈合。

方法

通过双能X线吸收法评估口服递增剂量GHB的雄性Sprague-Dawley大鼠(全身表面积烫伤≥40%)的身体组成。检测血清GH和IGF-1水平。对伤口横截面的伤口愈合变量进行半定量评分。

结果

在高剂量时,GH和IGF-1的递增升高与伤口边缘上皮形成及细胞层厚度的显著改善相关(p<0.005)。然而,身体组成与烧伤对照组相似。

结论

GHB可充分提高血清GH和IGF-1水平,在高剂量时显著改善上皮形成率和层厚度。大鼠烧伤模型中血清GH和IGF-1水平的升高幅度远大于人类。GHB可能通过提高内源性GH水平改善人类烧伤后的高代谢,尽管本研究仅证明上皮形成得到改善。

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