角质细胞生长因子-1在脓毒症大鼠肾脏的表达及意义

目的 探讨角质细胞生长因子-1(keratinocyte growth factor-1,KGF-1)在脓毒症大鼠肾脏的表达及意义.方法 将80只6周龄健康雄性Wistar大鼠随机分成手术组和假手术组(各40只).用盲肠结扎穿刺法制备脓毒症大鼠模型.两组分别在术后3h、6h、12h、24h和36h留取血液及肾脏标本,HE染色光镜观察大鼠肾脏病理学变化,测定血肌酐(Cr)、尿素氮(BUN)浓度及WBC计数,免疫组织化学SABC染色法检测KGF-1蛋白表达,实时荧光定量PCR法检测KGF-1mRNA的基因相对表达量.结果 与假手术组相比,手术组24h肾损伤最严重,可见肾小管空泡变性,大量中性粒细胞、淋巴细胞及单核细胞浸润、局部有点状出血、坏死;血Cr、BUN术后3h无明显升高,6h后升高,24h达峰值,36h略有下降,差异有统计学意义(P<0.01).KGF-1蛋白及基因表达6h最强,12h有所下降,24h出现第二次表达高峰,36h又有所下降,均明显高于假手术组(P<0.01).KGF-1mRNA与BUN成正相关(r=0.504,P<0.01),与Cr成正相关(r=0.382,P<0.05).结论 KGF-1在正常大鼠肾脏中即有表达,主要集中在髓质肾小管上皮细胞,皮质肾小管也有分布.脓毒症受损肾脏的KGF-1表达显著增强且与肾脏损伤程度呈正相关,推测KGF-1是影响感染后肾脏损伤修复的重要因素之一.

Abstract：

Objective To investigate the expression and significance of keratinocyte growth factor-1(KGF-1) in the kidneys of septic rats.Methods Eighty male Wistar rats were randomly divided into the sepsis group and sham operation group.Either group was divided into 3-hour,6-hour,12-hour,24-hour and 36-hour subgroups,with 8 rats in each.Sepsis models were established by cecum ligation perforation (CLP).The kidney and blood samples were respectively taken for pathological study.Serum creatinine (Cr) and blood urea nitrogen (BUN) level determination and leukocyte counting were performed.KGF-1 protein was detected by immunohistochemical method and the expression of KGF-1 genes by real time PCR.Results The renal tubules in sepsis group were injured most at 24h after operation,which were infiltrated by considerable neutrophilic granulocytes,leukomonocytes and mononuclear cells,with vacuolar degeneration,focal hemorrhage and necrosis under the light microscopy.Serum Cr and BUN increased from 6h after operation,and reached the peak at 24h after operation in sepsis group,which were significantly different in those of sham operation group (P< 0.01).Compared with sham operation group,the expression of KGF-1 protein and genes of sepsis group increased significantly and reached the peak at 6h after operation.KGF-1mRNA was positively correlated with BUN and Cr (r=0.504,P<0.01;r=0.382,P<0.05).Conclusion KGF-1 was also expressed in normal kidneys,mainly in tubule epithelial cells of renal medulla and also in that of renal cortex.The expression of KGF-1 in sepsis group was obviously higher than that of sham operation group,and was positively correlated with the degree of kidney damage after infection.KGF-1 was speculated to be one of the protective factors affecting the repair of impaired kidneys caused by infection.

Expression and significance of keratinocyte growth factor-1 in kidneys of septic rats

Objective To investigate the expression and significance of keratinocyte growth factor-1(KGF-1) in the kidneys of septic rats.Methods Eighty male Wistar rats were randomly divided into the sepsis group and sham operation group.Either group was divided into 3-hour,6-hour,12-hour,24-hour and 36-hour subgroups,with 8 rats in each.Sepsis models were established by cecum ligation perforation (CLP).The kidney and blood samples were respectively taken for pathological study.Serum creatinine (Cr) and blood urea nitrogen (BUN) level determination and leukocyte counting were performed.KGF-1 protein was detected by immunohistochemical method and the expression of KGF-1 genes by real time PCR.Results The renal tubules in sepsis group were injured most at 24h after operation,which were infiltrated by considerable neutrophilic granulocytes,leukomonocytes and mononuclear cells,with vacuolar degeneration,focal hemorrhage and necrosis under the light microscopy.Serum Cr and BUN increased from 6h after operation,and reached the peak at 24h after operation in sepsis group,which were significantly different in those of sham operation group (P< 0.01).Compared with sham operation group,the expression of KGF-1 protein and genes of sepsis group increased significantly and reached the peak at 6h after operation.KGF-1mRNA was positively correlated with BUN and Cr (r=0.504,P<0.01;r=0.382,P<0.05).Conclusion KGF-1 was also expressed in normal kidneys,mainly in tubule epithelial cells of renal medulla and also in that of renal cortex.The expression of KGF-1 in sepsis group was obviously higher than that of sham operation group,and was positively correlated with the degree of kidney damage after infection.KGF-1 was speculated to be one of the protective factors affecting the repair of impaired kidneys caused by infection.