Pediatric Institute for Critical Illness Research, Critical Care Center of Children's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200040, China.
World J Emerg Med. 2010;1(1):65-9.
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.
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 sacrificed 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.
In the LPS shock group, lung histopathology demonstrated destruction of the alveolar space,widening of the inter-alveolar space, inflammatory cell infiltration 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) as compared with the control group (1.17±0.22). The LPS shock group showed a more significant down-regualtion than the LPS+VIP group, but the difference was not statistically significant (P>0.05). In contrast, GRmRNA expression in the LPS+ VIP+GC group was significantly up-regulated at 6 hours and further at 24 hours (1.45±0.32 and 1.91±0.46 respectively) (P<0.05).
GrmRNA expression decreased in LPS induced lung injury in rats. Combined treatment with VIP and GC mitigated lung injury ang inflammation. The mechanism may be related to up-regulation of GR mRNA expression.
在严重脓毒症和感染性休克的情况下，一系列病理生理变化导致多器官功能障碍综合征。本研究旨在探讨内毒素（LPS）诱导休克后大鼠肺组织中糖皮质激素受体 mRNA 的表达。
将 56 只 SD 大鼠随机分为 4 组：LPS 休克组（n=16）、LPS+血管活性肠肽（VIP）组（n=16）、LPS+VIP+糖皮质激素（GC）组（n=16）和对照组（n=8）。通过静脉注射 LPS（10mg/kg）诱导 LPS 休克。在 LPS 注射后 15 分钟内，治疗组大鼠分别给予 VIP（5nmol/kg）或 VIP 和甲泼尼龙（3mg/kg）。对照组给予生理盐水代替 LPS。四组大鼠分别于注射后 6 小时和 24 小时处死，采集肺组织。光镜和电镜观察肺组织病理学变化，RT-PCR 评价肺组织 GRmRNA 表达。
LPS 休克组肺泡腔破坏，肺泡间隔增宽，炎性细胞浸润，间质水肿。然而，LPS+VIP 组和 LPS+VIP+GC 组的病理变化较 LPS 休克组轻。LPS 注射后 6 小时，LPS 组（0.72±0.24）和 LPS+VIP 组（0.88±0.27）GRmRNA 表达下调（P<0.05）与对照组（1.17±0.22）相比。LPS 休克组的下调程度明显大于 LPS+VIP 组，但差异无统计学意义（P>0.05）。相反，LPS+VIP+GC 组 6 小时和 24 小时 GRmRNA 表达明显上调（分别为 1.45±0.32 和 1.91±0.46）（P<0.05）。
LPS 诱导的大鼠肺损伤中 GrmRNA 表达降低。VIP 和 GC 联合治疗减轻了肺损伤和炎症。其机制可能与 GRmRNA 表达上调有关。
