Glucocorticoid receptor expression on acute lung injury induced by endotoxin in rats.

BACKGROUND: In cases of severe sepsis and septic shock, a series of pathophysiological changes lead to multiple organ dysfunction syndrome.This study aimed to investigate the expression of glucocorticoid receptor mRNA in the rat lung following endotoxin (LPS) induced shock. METHODS: Totally 56 SD rats were randomly divided into 4 groups: LPS shock group ( n=16), LPS+vasoactive intestinal peptide group(VIP) group, ( n=16), LPS+VIP+ glucocorticoid (GC) group, (n=16),and control group ( n=8). LPS shock was induced by intravenous injection of LPS (10 mg/kg) in rats. Within 15 minutes after LPS injection, rats in the treatment groups received VIP (5 nmol/kg) or VIP and methylprednisolone (3 mg/kg). The control group was given normal saline instead of LPS. The rats of the four groups were sacrifi ced at 6 hours,24 hours after injection respectively, and the lung tissues were collected. Pathological changes of the lungs were examined by light microscopy and electron microscopy. GRmRNA expression in the lung tissues was evaluated by RT-PCR. RESULTS: In the LPS shock group, lung histopathology demonstrated destruction of the alveolar space,widening of the inter-alveolar space, infl ammatory cell infi ltration and interstitial edema. However,pathological changes in the LPS+ VIP group and LPS+ VIP+GC group were milder than those in the LPS shock group. Six hours after LPS injection, GR mRNA expression was down-regulated in the LPS group (0.72± 0.24) and LPS+ VIP group (0.88±0.27) ( P 0.05). In contrast, GRmRNA expression in the LPS+ VIP+GC group was signifi cantly up-regulated at 6 hours and further at 24 hours (1.45±0.32 and 1.91±0.46 respectively) ( P<0.05). CONCLUSION: GrmRNA expression decreased in LPS induced lung injury in rats. Combined treatment with VIP and GC mitigated lung injury ang infl ammation. The mechanism may be related to up-regulation of GR mRNA expression.