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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。
Objective To observe the expression of nephrin and P-cadherin in glomerular podocyte of neonatal rat with sepsis and the effect of dexamethasone on them, in order to investigate the mechanism of proteinuria in sepsis. Methods Twenty-four newborn Wistar rats were enrolled in this study. Sepsis models were induced by intraperitoneal injection of lipopolysaccharide (LPS) and were randomly divided into sepsis group (SE group, n = 12), dexamethasone group Group, n = 12). DE group rats were given dexamethasone 0.3 mg / kg after intraperitoneal injection of LPS for 12 h. Another 10-day-old Wistar rats were used as the control group (NC, n = 10). Serum C-reactive protein (CRP), procalcitonin (PCT), neutrophil gelatinase-associated apolipoprotein (NGAL), 24 h urine protein (24 hUP) (UPC). The expressions of nephrin and P-cadherin mRNA and protein in glomerulus were detected by RT-PCR and Western-blotting. Results Compared with NC group, the levels of CRP, PCT, NGAL and 24 h UP in SE group were significantly increased (all P <0.01), while there was no significant difference in UPC. Nephrin, P- cadherin mRNA and protein expression was significantly down-regulated. Dexamethasone significantly improved LPS induced CRP, PCT, NGAL, 24 h UP increased, maintaining nephrin, P-cadherin mRNA and protein expression, UPC no significant effect on excretion. Conclusion Dexamethasone can reduce the systemic inflammatory response, restore glomerular nephrin, P-cadherin mRNA and protein expression, reduce proteinuria.