实验性急性呼吸窘迫综合征大鼠脑组织Gq蛋白-肌醇磷脂途径的变化

目的：探讨急性呼吸窘迫综合征（ARDS）大鼠脑组织中Gq蛋白-肌醇磷脂途径的变化及其作用。方法：健康雄性40只 Wistar 大鼠随机分为油酸组（OA组）和对照组。OA组由大鼠尾静脉注射OA 0.2 mL/kg （2 min内）复制ARDS模型,根据不同观测时点分为30 min、60 min、90 min和120 min 4个亚组。检测各组大鼠平均动脉血压（MABP）,血气,血浆和脑组织丙二醛含量及乳酸脱氢酶（LDH）、肌酸激酶（CK）活性。免疫印迹法检测各组大鼠脑组织中的Gq/11蛋白α活性亚基以及磷脂酶C （PLC）含量。结果：与对照组相比,OA组MABP、PaO2明显降低（P<0.05）。OA 90 min和120 min组血浆和脑组织的MDA含量和LDH活性明显升高（P<0.05）。OA组血浆CK活性较对照组明显升高（P<0.05）,脑组织CK活性在OA 60 min组升高（P<0.05）,随后在90 min和120 min组降低（P<0.05）。脑组织Gαq/11蛋白在OA 60 min、90 min和120 min组明显升高（P<0.05）。OA组脑组织PLC表达明显上调（P<0.05）。脑组织Gαq/11蛋白表达与PaO2 的改变呈负相关（r=-0.579,P<0.05）,与脑组织MDA变化呈正相关（r=0.538,P<0.05）,与脑组织LDH的变化亦呈正相关（r=0.624,P<0.05）。结论：ARDS时Gq蛋白-肌醇磷脂信号通路活性增强可能参与了脑组织的损伤。

Change of Gq protein-phosphatidyl inositol signaling in brain of rats with acute respiratory distress syndrome

AIM: To study the change of Gq protein-phosphatidyl inositol signaling in the brain of rats with acute respiratory distress syndrome (ARDS). METHODS: Forty male Wistar rats were randomly divided into oleic acid groups (OA groups of 30 min, 60 min, 90 min and 120 min exposure) and control group. The ARDS model in rats was reproduced by intravenous injection of oleic acid (0.2 mL/kg in 2 min). The mean arterial blood pressure (MABP), blood gas indexes, malondialdehyde (MDA), lactate dehydrogenase (LDH) and creatine kinase (CK) in plasma and brain tissues were measured. Gαq/11 protein and phospholipase C in brain tissues were detected by Western blotting. RESULTS: Compared to control group, MABP and PaO2 in all OA groups obviously decreased (P<0.05). MDA concentration and LDH activity in plasma and brain tissues of OA rats at time points of 90 min and 120 min were significantly higher than those in the controls (P<0.05). The CK activity in plasma of all OA groups increased (P<0.05). The CK activity in the brain tissues peaked at 60 min after OA exposure (P<0.05) and then decreased at 90 min and 120 min after treated with OA (P<0.05). Compared to control group, the concentration of Gαq/11 protein in the brain tissues of OA 60 min, 90 min and 120 min groups, and PLC concentration in the brain tissues of all OA groups obviously increased (P<0.05). A negative correlation between the change of Gαq/11 protein in the brain tissues and PaO2 (r=-0.579, P<0.05), a positive correlation between the change of Gαq/11 protein and MDA in the brain tissues (r=0.538, P<0.05), and a positive correlation between the change of Gαq/11 protein and LDH in the brain tissues (r=0.624, P<0.05) were observed. CONCLUSION: Up-regulation of Gq protein-phosphatidyl inositol signaling in the brain may play a role in the brain injury during ARDS.