Ligustrazine attenuates acute lung injury after burn trauma
Introduction
One of the characteristics of partial thickness thermal trauma is the development of microvascular injury at the dermal burn site and, distantly, in the lungs. Pulmonary pathology in major thermal injury is found in 30–80% of burn fatalities [1]. Acute lung injury is a common complication in patients with extensive burns in which the burned area exceeds 30% of the total body surface area (TBSA) [2]. It has been well documented that respiratory complications are the major cause of morbidity and mortality in burned patients who are admitted to the hospital, especially in combination with smoke inhalation injury [3]. The chemokines, such as interleukin-8 (IL-8), have been demonstrated to play an important role in the development of serious infections and various inflammatory diseases in humans.
IL-8, a prototype of the C-X-C chemokine family, associated with acute inflammation, was elevated in human wounds [4], [5]. IL-8 was reported to modulate the functions of numerous inflammatory cells involved in the repair process [6] and has been described as a potent chemoattractant for neutrophils [7]. Partial-thickness skin burns have been shown to induce neutrophil-dependent microvascular injury both locally (skin) and systemically (lung) [8]. Lung injury secondary to thermal trauma to skin is known to be neutrophil-dependent as shown by neutrophil depletion experiments [9]. Previous studies found that when the cytokine concentrations were correlated with size of burn the circulating concentrations of IL-8 were higher in patients with TBSA burn of 40% or more, or TBSA third degree burn of 30% or more than in those with smaller injuries. In addition, there was a positive correlation between circulating IL-8 and size of burn [10].
Ligustrazine (tetramethy pyrazine), a component contained in Chuanxiong (Ligustrum chuanxiong Hort, one of the ABCRBS herbs), is widely applied in the treatment of vascular diseases in China [11]. Ligustrazine has been demonstrated to have protective effects against kidney ischemia-reperfusion injury in rats and prevent acute myocardial infarction and cerebrovascular accidents in humans [12], [13]. However, there are few reports regarding the effect of Ligustrazine on organ injury after thermal injury.
In this study, we have examined the effect of Ligustrazine on burn-induced lung injury as well as the release of IL-8 in severely burned rats to define its role in neutrophil-mediated injury to the lung after thermal trauma.
Section snippets
Animals
Male Wistar rats (weight range 225–250 g), purchased from the Laboratory Animal Center, Anhui Medical University, were used for the study. The animals were housed in separate cages in a temperature-controlled room with alternating 12 h light/12 h dark cycles, and were allowed 1 week to acclimate to their surroundings. Rats were fed a standard animal diet; food and tap water would be available at will throughout the experimental protocol.
Burn procedure
Two days before receiving burns, external jugular catheters
Pulmonary microvascular permeability
At 24 h after a 30% TBSA full-thickness burn, the BAL to-serum ratio of FITC was elevated in the control group in comparison with the sham group (43.6 ± 6.5 versus 12.8 ± 1.6). In the Ligustrazine group, this increase was significantly attenuated (P < 0.01 versus control; Fig. 1).
Lung wet/dry weight ratio
Lung wet/dry weight ratio was significantly higher at 24 h after burn injury (5.4 ± 0.14 versus 5.12 ± 0.04; P < 0.01) in the control group compared with the sham group. In the Ligustrazine group the ratio was 5.23 ± 0.07, which was
Discussion
Acute lung injury is a major cause of morbidity in fire victims. Experimental studies in rats have demonstrated that a second-degree burn of skin of the lower back and flanks and involving 28–30% of the total body surface area of rats results in a sequence of events which ultimately cause lung injury [9]. In addition, previous experimental work has suggested that the injury of other organs and tissues distant from the burn site may attribute to pulmonary dysfunction [20]. Although the lung
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