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高剂量维生素C可抵消热损伤大鼠的负性组织间液静水压和早期水肿形成。

High dose vitamin C counteracts the negative interstitial fluid hydrostatic pressure and early edema generation in thermally injured rats.

作者信息

Tanaka H, Lund T, Wiig H, Reed R K, Yukioka T, Matsuda H, Shimazaki S

机构信息

Department of Traumatology and CCM, Kyorin University, Mitaka, Tokyo, Japan.

出版信息

Burns. 1999 Nov;25(7):569-74. doi: 10.1016/s0305-4179(99)00073-x.

Abstract

BACKGROUND AND OBJECTIVE

edema formation after thermal injury is rapid and fulminant within the first hour after injury and increased microvascular permeability has been claimed to be the main responsible mechanism. An acute decrease in interstitial fluid hydrostatic pressure (P(if)) down to -150 mm Hg has recently been reported in dermal burns. This strong negative tissue pressure creates a 'suction' on the fluid in the capillaries. Furthermore, high dose vitamin C (VC) has been shown to reduce postburn edema and fluid requirements following major burn injuries. This led to the present study, aimed at investigating whether VC administered after thermal injury in rats, could attenuate the strongly negative P(if). Edema volume was measured by total tissue water content (TTW) and extravasation of albumin (Ealb).

STUDY DESIGN

a prospective, open experimental study.

MATERIALS AND METHODS

pentobarbital-anesthetized rats received either a full-thickness burn injury covering 10% of total body surface area, or a sham burn. The rats were given VC or equal volumes normal saline (NS) either before the burn, 5 or 30 min after the injury. VC (25 mg/ml in NS, osmolality 272 mOsm/l) was administered as a bolus (66 mg/kg) followed by infusion (33 mg/kg/h). The animals were divided into 7 groups (6 animals in each) according to the timing of VC/NS administration: (1) VC-preburn, (2) VC-5 min postburn, (3) VC-30 min postburn, (4) NS-preburn, (5) NS-5 min postburn, (6) NS-30 min postburn and (7) VC-pre sham burn group. All groups were duplicated for series I and II.

MEASUREMENTS

in series I; P(if) was measured using a sharpened glass micropipette connected to a servo-controlled counter pressure system. Measurements were averaged in the following time periods: preburn, 5-20, 21-40, 41-60 and 61-90 min postburn. In series II; Ealb and TTW were measured in burned and non-burned skin by radio-labelled albumin and wet-dry weights, respectively.

RESULTS

in the sham control group (VC-pre-sham burn), P(if) ranged between -1 and -2 mm Hg and did not change throughout the experimental period. In the NS group (placebo), P(if) fell to -46.8 +/- 10.1 (1 S.D.) mm Hg at 5-20 min after the injury and were -23.1 +/- 13.4 and -11.6 +/- 4.1 mm Hg at 21-40 and 41-60 min postburn. P(if) returned to preburn values at 61-90 min post injury. In the VC groups, there was a marked attenuation of the negative P(if) to average -10.1 +/- 11.8 mm Hg at 5-20 min, -2 +/- 1.7 and -0.6 +/- 1.2 mm Hg at 21-40 and 41-60 min after injury, respectively (all p < 0.01 compared to NS). TTW in burned skin of the NS-5 min groups was 3.12 +/- 0.28, VC5-min group was 2.57+/-0.69 and VC sham was 1.77+/-0.19 ml/g DW, respectively (p < 0.01 compared to sham control for all values). In all the VC-groups TTW values were higher than sham control and lower than in the corresponding NS-groups (p > 0.05 both ways). No statistical significant differences were found between Ealb-values in the VC- and NS-groups.

CONCLUSION

high-dose vitamin C attenuates the development of strongly negative P(if) in burned dermis and reduces the edema as measured by TTW. No significant change in Ealb was found. Vitamin C was thus found to have potential beneficial effects on the acute postburn edema generation.

摘要

背景与目的

热损伤后水肿形成迅速,在损伤后第一小时内即迅猛发展,微血管通透性增加被认为是主要的致病机制。最近有报道称,皮肤烧伤后间质液静水压(P(if))会急剧下降至 -150 mmHg。这种强烈的负组织压力会对毛细血管内的液体产生“抽吸”作用。此外,高剂量维生素C(VC)已被证明可减轻严重烧伤后的烧伤后水肿和液体需求量。由此开展了本研究,旨在探究热损伤后给予大鼠VC是否能减轻强烈的负P(if)。通过总组织含水量(TTW)和白蛋白外渗(Ealb)来测量水肿体积。

研究设计

一项前瞻性、开放性实验研究。

材料与方法

用戊巴比妥麻醉的大鼠,一部分接受占体表面积10%的全层烧伤,另一部分接受假烧伤。在烧伤前、损伤后5分钟或30分钟给予大鼠VC或等量的生理盐水(NS)。VC(溶于NS中,浓度为25 mg/ml,渗透压为272 mOsm/l)先静脉推注(66 mg/kg),随后持续输注(33 mg/kg/h)。根据VC/NS给药时间将动物分为7组(每组6只):(1)烧伤前给予VC组,(2)烧伤后5分钟给予VC组,(3)烧伤后30分钟给予VC组,(4)烧伤前给予NS组,(5)烧伤后5分钟给予NS组,(6)烧伤后30分钟给予NS组,(7)烧伤前给予VC的假烧伤组。所有组均重复进行系列I和系列II实验。

测量指标

在系列I中,使用连接到伺服控制反压系统的尖锐玻璃微吸管测量P(if)。在以下时间段进行测量并求平均值:烧伤前、烧伤后5 - 20分钟、21 - 40分钟、41 - 60分钟和61 - 90分钟。在系列II中,分别通过放射性标记白蛋白和湿重-干重法测量烧伤皮肤和未烧伤皮肤的Ealb和TTW。

结果

在假对照组(烧伤前给予VC的假烧伤组)中,P(if)在 -1至 -2 mmHg之间,整个实验期间无变化。在NS组(安慰剂组)中,损伤后5 - 20分钟P(if)降至 -46.8 ± 10.1(1个标准差)mmHg,烧伤后21 - 40分钟和41 - 60分钟分别为 -23.1 ± 13.4 mmHg和 -11.6 ± 4.1 mmHg。损伤后61 - 90分钟P(if)恢复到烧伤前值。在VC组中,负P(if)明显减轻,损伤后5 - 20分钟平均为 -10.1 ± 11.8 mmHg,21 - 40分钟和41 - 60分钟分别为 -2 ± 1.7 mmHg和 -0.6 ± 1.2 mmHg(与NS组相比所有p < 0.01)。NS - 5分钟组烧伤皮肤的TTW为3.12 ± 0.28,VC5 - 分钟组为2.57 ± 0.69,VC假烧伤组为1.77 ± 0.19 ml/g干重,(所有值与假对照组相比p < 0.01)。在所有VC组中,TTW值均高于假对照组且低于相应的NS组(两种比较方式p > 0.05)。VC组和NS组的Ealb值之间未发现统计学显著差异。

结论

高剂量维生素C可减轻烧伤真皮中强烈负P(if)的发展,并降低通过TTW测量的水肿程度。未发现Ealb有显著变化。因此发现维生素C对烧伤后急性水肿的产生具有潜在的有益作用。

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