地塞米松对脓毒症新生大鼠nephrin的影响

目的观察脓毒症新生鼠肾小球足细胞裂孔隔膜蛋白nephrin、P-cadherin的表达及地塞米松对两者的影响,以探讨脓毒症蛋白尿的发生机制。方法新生10 d Wistar大鼠24只,采用脂多糖(LPS)腹腔内注射的方法诱导脓毒症模型,随机分为脓毒症组(SE组,n=12),地塞米松治疗组(DE组,n=12),DE组大鼠腹腔注射LPS 12 h后给予地塞米松0.3 mg/kg。另设出生10 d Wistar鼠为对照组(NC,n=10)。注射LPS 48 h后分别测定血清C-反应蛋白(CRP)、降钙素原(PCT)、中性粒细胞明胶酶相关载脂蛋白(NGAL),24 h尿蛋白(24 hUP)及尿足细胞(UPC)排泄水平;RT-PCR和Western-blotting检测肾小球nephrin、P-cadherin mRNA和蛋白质的表达。结果与NC组相比,SE组大鼠的CRP、PCT、NGAL、24 h UP水平均显著升高,差异有统计学意义(P均<0.01),UPC差异无统计学意义;nephrin、P-cadherin mRNA及蛋白质的表达明显下调。地塞米松明显改善LPS引起的CRP、PCT、NGAL、24 h UP升高,维持nephrin、P-cadherin mRNA及蛋白质的表达,对UPC的排泄无明显影响。结论地塞米松可减轻全身炎症反应,恢复肾小球nephrin、P-cadherin mRNA和蛋白质的表达,减轻蛋白尿。

Dexamethasone ameliorates the expression of nephrin in neonate rats with sepsis

Objective To observe the effects of dexamethasone on the expression of nephrin and P-cadherin at the slit diaphragm of the glomerular podocytes in neonate rats with sepsis,and investigate the mechanism of proteinuria in sepsis.Methods Twenty-four 10-day-old Wistar rats were intraperitoneally injected with a single dose of lipopolysac-charide(LPS)to induce sepsis model,and randomly divided into sepsis group(SE,n = 12)and SE plus dexamethasone treatment group(DE,n = 12).Rats in DE group were administrated dexamethasone(0.3 mg/kg)by intraperitoneal injection at 12 h after intraperitoneal injection of LPS.Another 10-day-old Wistar rats were served as control group(NC,n=10).At 48 h after LPS was intraperitoneally injected,serum C-reactive protein(CRP),procalcitonin(PCT),neutrophil gelatinase-associated lipocalin(NGAL),24 h urinary protein(24 h UP)and urinary podocytes(UPC)were measured.The expressions of glomerular nephrin and P-cadherin mRNA and proteins were detected by RT-PCR and Western-blotting respectively.Results CRP,PCT,NGAL and 24 h UP were significantly higher in SE group than those in NC group(P < 0.01),and UPC had no significant difference.The nephrin and P-cadherin mRNA and proteins expressions were decreased in SE group than those in NC group.Dexamethasone significantly reduced CRP,PCT,NGAL,24 h UP levels which were induced by LPS challenge,and preserved the expressions of nephrin and P-cadherin mRNA and proteins,but had no effect on the excretion of UPC.Conclusions Dexamethasone can ameliorate systemic inflammatory response,restore the expressions of glomerular nephrin and P-cadherin mRNA and proteins,and reduce proteinuria.