维生素D对脂多糖致急性肺损伤大鼠肺组织血管紧张素转化酶2和维生素D受体表达水平的影响

目的 观察维生素D(vitamin D,Vit D)对脂多糖(lipopolysaccharide,LPS)致Wistar大鼠急性肺损伤(acute lung injury,ALI)肺组织中血管紧张素转化酶2(angiotensinconverting enzyme 2,ACE2)和维生素D受体(vitamin D receptor,VDR)表达水平的影响.方法 采用尾静脉注射LPS方法制备大鼠ALI模型;将30只健康雄性Wistar大鼠随机(随机数字法)分为6组:正常对照组(NC组)、LPS组:尾静脉注射LPS 5mg/kg、Vit D组:给予Vit D活性形式(骨化三醇)25 μg/kg连续灌胃3d和(LPS+ Vit D) 1-3组:分别于骨化三醇1μg/kg、5μg/kg、25 μg/kg灌胃3d后尾静脉注射LPS 5mg/kg,所有大鼠于注射LPS的24 h后进行后续实验.分别观察大鼠一般情况,肺组织病理及肺干/湿重比变化、肺组织中VDR、ACE2蛋白及基因水平的表达.结果 LPS组大鼠病态表现(呼吸浅快、精神萎靡、口鼻可见血性分泌物)明显,(LPS+ VitD) 1-3组病态表现和肺组织病理损伤均较LPS组明显减轻.LPS组VDR和ACE2蛋白及基因水平的表达均较NC组和Vit D组显著降低(P＜0.05),(LPS+ VitD) 1-3组各组VDR和ACE2蛋白及基因水平的表达均较LPS组有所升高(P＜0.05),但仍显著低于Vit D组(P＜0.05),其中(LPS+ Vit D) 1-3组各组VDR蛋白及基因水平的表达差异无统计学意义(P＞0.05),ACE2的表达差异有统计学意义(P＜0.05).结论 Vit D能使LPS致ALI大鼠肺组织中ACE2和VDR蛋白及基因表达水平增加,故此推测ACE2和VDR表达增加可能对ALI的发生、发展起保护作用.

Effect of vitamin D on ACE2 and vitamin D receptor expression in rats with LPS-induced acute lung injury

Objective To observe the effect of vitamin D on angiotensin converting enzyme 2 (ACE2) and vitamin D receptor (VDR) expression in Wister rat models of acute lung injury (ALI) induced by using lipopolysaccharide (LPS).Methods The rat models of ALI induced by LPS were established by intravenous injection of LPS via tail vein.Thirty Wistar rats were randomly (random number) divided into 6 groups:normal control group,LPS group,calcitriol (25 μg/kg) group,LPS + calcitriol 1 μg/kg group,LPS + calcitriol 5 μg/kg group and LPS + calcitriol 25 μg/kg group.The changes of general condition,lung pathology,lung wet/dry weight ratio and changes of VDR mRNA and ACE2 mRNA expressions and protein levels of VDR and ACE2 in rats were observed.Results The clinical manifestations (rapid shallow breathing;listlessness;the oral and nose hemorrhage) in LPS group were obvious,and the clinical manifestations and pathological changes of lung tissues in the LPS + calcitriol groups were significantly milder than those in LPS group.The expressions of VDR mRNA and ACE2 mRNA in LPS group was significantly lower than those in normal control group and calcitriol group (P ＜ 0.05).The expressions of VDR mRNA and ACE2 mRNA in LPS + calcitriol groups were significantly higher than those in LPS group (P ＜ 0.05),and lower than those in normal control group significantly (P ＜ 0.05).Meanwhile,among LPS + calcitriol groups,there was no significant difference in expression of VDR mRNA (P ＞ 0.05) and there was significant difference in ACE2 mRNA expression (P ＜ 0.05).Conclusions Calcitriol can increase the expressions of VDR mRNA and ACE2 mRNA and protein levels of VDR and ACE2 in rat models of LPS-induced ALI,thus suggesting the increased expressions of ACE2 mRNA and VDR mRNA playing a role in protection against the development of ALI.