黄芪多糖对脓毒血症大鼠模型肾上腺皮质醇相关合成酶及维生素D轴的影响

Effects of Astragalus Polysaccharides on Adrenal Cortisol Related Synthases and Vitamin D Axis in Septic Rats

目的探讨黄芪多糖对脂多糖诱导的脓毒血症肾上腺损伤大鼠血清皮质醇、25(OH)D_(3)水平及肾上腺皮质维生素D受体(VDR)、类固醇急性调节蛋白(STAR)、21α-羟化酶(CYP21)、17α-羟化酶(CYP17A1)mRNA表达情况的影响。方法将60只雄性SD大鼠适应性喂养7 d后,随机分为对照组、模型组、黄芪多糖高(200 mg/kg)、中(100 mg/kg)、低(50 mg/kg)剂量组及维生素D(3×10^(-5)mg/kg)组。分别对每组大鼠以相应剂量进行为时7 d的灌胃给药,并在造模前15 min和后6 h腹腔注射给药,12 h后取样。ELISA法检测大鼠血清皮质醇和25(OH)D_(3)水平,HE染色法观察大鼠肾上腺皮质组织病理学改变,RT-PCR技术检测大鼠肾上腺皮质VDR、STAR、CYP21、CYP17A1mRNA的表达情况。结果相较对照组,模型组血清皮质醇和25(OH)D_(3)水平显著下降(P<0.05),肾上腺组织皮质区出现较明显的炎症反应,VDR、STAR、CYP21、CYP17A1 mRNA表达量下降(P<0.05)。相较模型组,维生素D组及黄芪多糖高、中、低剂量组皮质醇水平上升(P<0.05),维生素D组及黄芪多糖高、中剂量组25(OH)D_(3)水平上升(P<0.05);黄芪多糖高、中剂量组肾上腺皮质区病变程度减轻;维生素D组及黄芪多糖高、中剂量组肾上腺VDR、STAR、CYP21、CYP17A1 mRNA表达量上升(P<0.05)。结论黄芪多糖可能通过维生素D轴调节皮质醇相关合成酶表达,从而发挥对脓毒血症大鼠肾上腺皮质的保护作用。

Objective To investigate the effects of Astragalus polysaccharide(APS)on the serum levels of cortisol and 25(OH)D_(3),and the expressions of vitamin D receptor(VDR),Steroid Acute Regulatory protein(STAR),21α-hydroxylase(CYP21)and 17α-hydroxylase(CYP17 A1)mRNA in rats with sepsis into adrenal injury induced by lipopolysaccharide(LPS).Methods Sixty male SD rats were randomly divided into blank control group,model group,APS high(200 mg/kg),medium(100 mg/kg)and low(50 mg/kg)dose groups and vitamin D group(3×10^(-5)mg/kg).The rats in each group were given a 7 day preventive intervention at a corresponding dose,administered 15 minutes before and 6 hours after modeling,and sampled 12 hours later.Serum cortisol and 25(OH)D_(3)levels were detected by ELISA.Histopathological changes of adrenal cortex were observed by HE staining.The expressions of VDR,STAR,CYP21 and CYP17 A1 mRNA in adrenal cortex were detected by RT-PCR.Results Compared with those of the blank control group,the levels of serum cortisol and 25(OH)D_(3)in the model group were significantly decreased(P<0.05).There was obvious inflammatory reaction and part of cell damage appeared in the cortex of adrenal tissue.The expressions of VDR,STAR,CYP21 and CYP17 A1 mRNA were decreased(P<0.05).Compared with those of the model group,the cortisol levels of vitamin D group and APS high,medium and low dose groups were increased(P<0.05),and 25(OH)D_(3)level was increased in vitamin D group and APS high and medium dose groups(P<0.05).The pathological changes of adrenal cortex in high and medium dose groups of APS were alleviated.The expressions of VDR,STAR,CYP21,CYP17 A1 mRNA in vitamin D group and APS high and medium dose groups were increased(P<0.05).Conclusion APS may regulate the expressions of cortisol related synthases through vitamin D axis,and thus playing a protective role in adrenal cortex of septic rats.