雌孕激素对ALI大鼠α-ENaC、BNP、TNF-α表达的影响

Effects of Estradiol and Progestogen on Rat α-epithelial Na^+ Channel,Brain Natriuretic Peptide,Tumor Necrosis Factor-α with Arcute Lung Injury

目的:研究雌孕激素对ALI大鼠II型肺泡上皮细胞钠通道(epithelial Na+channel,ENaC)α亚基,血清脑钠肽(brain natriuretic peptide,BNP)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)表达的影响,探讨肺泡内液体清除的机制。方法:雌性未成年SD大鼠30只,随机分为3组:对照组(静脉注入生理盐水8 mL/kg)、ALI模型组(静脉注入油酸0.1 mL/kg)、雌孕激素联合组(在油酸注入前12 h、36 h皮下注射1∶1 000雌孕激素混合液0.1 mL)。建模后6 h处死大鼠,观察肺组织病理改变,测定肺湿重/干重比值、肺系数,肺组织匀浆中α-ENaC mRNA及蛋白的表达及血清BNP、TNF-α的表达。结果:与对照组比较,模型组出现明显肺水肿、出血及炎性细胞浸润,肺湿重/干重比值、肺系数及血清中BNP、TNF-α表达增加,而α-ENaC mRNA及蛋白明显降低(P<0.01);雌孕激素联合组与ALI模型组比较,肺水肿、出血及炎性细胞浸润要轻,肺湿重/干重比值、肺系数、BNP下降,α-ENaC mRNA及蛋白增加(P<0.05)。结论:雌孕激素联合治疗可上调α-ENaC mRNA及蛋白的表达,减少BNP表达,促进肺泡内液体的清除,为ALI/急性呼吸窘迫综合症(ARDS)的治疗和监控提供新的方法。

Objective：To study the effects of 1713-estradio1 and progestogen on rat type Ⅱ alveolar α-epithelial Na＋ channel （ct-ENaC）, serum brain natriuretic peptide （BNP）,tumor necrosis factor-α （TNF-α） with arcute lung injury （ALI） and investigate the mechanism on the clearance of alveolar fluid. Method：30 immature female SD rats were ran- domly assigned into 3 groups： control group （injected with 8 mL/kg saline via venous） ,acute lung injury group （injec-ted with 0.1 mL/kg oleic acid via venous） , 1713-estradiol and progestogen combination group （injected subcutaneously with 1713-estradiol and progestogen mixed liquor 0.1 mL with the ratio of 1：1 000 at 12 h,36 h before oleic acid injec- tion）. All the rats were sacrificed at 6 h of oleic acid injection. The changes of lung pathology were observed,the wet/dry ratio,the lung coefficient,the expression of α-ENaC mRNA and protein and the level of serum BNP,TNF-α were deter- mined. Result：Compared with control group, obviously pulmonary edema,bleeding,inflammatory cell infiltrate were ob- served in ALl model group. The wet/dry ratio,the lung coefficient,the level of serum BNP and TNF-α increased signifi- cantly in ALI model group （P 〈 0.01 ） ,but the expression ofα-ENaC mRNA and protein decreased （P 〈 0.01 ）. Com- pared with ALI model group,the extent of pulmonary edema,bleeding,inflammatory cell infiltrate decreased markedly in combination group. The wet/dry ratio,the lung coefficient,serum BNP dec,eased significantly （P 〈 0.05 ） , but α-ENaC mRNA and protein increased significantly in combination group （P 〈 0.05 ）. Conclusion： 1713-estradiol and progesto- gen can upgradeα-ENaC mRNA and protein with ALI rat and decrease the expression of BNP, promote the clearance of alveolar fluid, provide a new method for the cure and monitoring of ALL/acute respiratory distress syndrome （ARDS）.