1-磷酸鞘氨醇信号对慢性阻塞性肺疾病大鼠肺泡扩大作用的影响

Effect of sphingosine-1 signal on alveolar enlargement in COPD rats

目的探讨1-磷酸鞘氨醇信号对大鼠肺泡扩大作用的影响。方法将大鼠随机分为烟雾组、药物组、烟雾+药物组及对照组,烟雾组和烟雾+药物组建立大鼠慢性阻塞性肺疾病(COPD)模型,烟雾+药物组和药物组在给予1-磷酸鞘氨醇受体激动剂灌胃,观察各组大鼠肺组织病理改变并进行评分、检测大鼠肺组织caspase-3蛋白、大鼠肺组织细胞凋亡情况,同时检测肺组织中磷酸化细胞外信号调节蛋白激酶(pERK)和磷酸化丝氨酸/苏氨酸激酶(pAkt)的表达。结果(1)烟雾组大鼠症状最重,病理评分高,烟雾+药物组较烟雾组症状及病理改变明显减轻。(2)凋亡指数结果:烟雾组(40.1±6.5)、药物组(10.2±1.87)、烟雾+药物组(24.1±3.84)及对照组(15.5±2.55),caspase-3阳性细胞计数百分比及染色强度评分总分:烟雾组(5.3±0.67)为强阳性,烟雾+药物组(3.1±0.73)为阳性,药物组(1.2±0.91)及对照组(0.8±0.63)均为阴性。(3)烟雾+药物组中大鼠肺组织中Akt、ERK表达量最大,药物组次之,烟雾组中此两种蛋白表达最低。结论通过实验得出1-磷酸鞘氨醇信号可通过抑制肺组织细胞凋亡进而影响肺气肿的形成,进一步改善COPD患者的症状及病理改变,其具体机制可能与1-磷酸鞘氨醇信号激活S1P/Akt/ERK信号通路有关。

Objective To investigate the effect of sphingosine-1 signal on alveolar enlargement in rats.Methods Rats were randomly divided into smoke group,drug group,smoke+drug group and control group.Rat COPD models were established in smoke group and smoke+drug group.Smoke+drug group and drug group were given sphingosine 1-phosphate receptor agonist by gastric perfusion.The pathological changes of lung tissue were observed and scored,caspase-3 protein in lung tissue of rats was detected,and apoptosis of lung tissue of rats was detected.The expressions of phosphorylated serine/threonine kinase(pERK)and phosphorylated protein serine/threonine kinase(pAkt)in lung tissues were detected.Results(1)The smoke group had the most severe symptoms and higher pathological scores.The smoke+drug group had significantly less symptoms and pathological changes than the smoke group.(2)The results of apoptotic index:smoke group(40.1±6.5),drug group(10.2±1.87),smoke+drug group(24.1±3.84)and control group(15.5±2.55).The percentage of Caspase-3 positive cells and total score of staining intensity:smoke group(5.3±0.67)was strongly positive,smoke+drug group(3.1±0.73)was positive,drug group(1.2±0.91)and control group(0.8±0.63)were negative.(3)The expressions of Akt and ERK were the highest in the smoke+drug group,followed by the drug group,and the lowest in the smoke group.Conclusions 1-sphingosine phosphate(sphingosine phosphate)signal can inhibit the formation of pulmonary emphysema by inhibiting the apoptosis of lung tissue and further improve the symptoms and pathological changes of COPD.The specific mechanism can be related to the activation of the S1P/Akt/ERK signal pathway of 1-sphingosine phosphate signal and provide a new idea for the treatment of COPD.