幼鼠肾小管间质损伤早期AT_1R介导JAK_2/STAT_3蛋白表达及其相关性  

Expression of JAK_2/STAT_3 protein mediated by angiotensin Ⅱ type 1 receptor signal in early stage of tubulointerstitial lesions in rats and their relations

作　　者：郭虹[1] 马宏[2] 殷爱云[3] 

机构地区：[1]山西医科大学儿科系,太原030001 [2]山西医科大学第一临床医学院儿科 [3]连云港市第二人民医院儿科

出　　处：《山西医科大学学报》2008年第9期807-810,共4页Journal of Shanxi Medical University

摘　　要：目的探讨幼年大鼠肾小管间质损伤早期肾组织AT1R介导跨膜信号传导通路中JAK2/STAT3信号分子表达的趋势、相关性及给予苯那普利和氯沙坦干预治疗的影响。方法3周龄幼年Wistar雄性大鼠72只,随机分为对照组(n=24)、UUO未治疗组(n=24)和UUO治疗组(n=24)。以单侧输尿管梗阻模型(UUO模型)作为实验模型,于治疗后第3,7,14,28天取病变肾脏石蜡包埋并切片。采用免疫组化方法检测大鼠肾组织AT1、JAK2、STAT3蛋白的表达,并从时相表达趋势上评价AT1R与JAK2/STAT3表达的相关性。结果UUO未治疗组3 d时三种蛋白表达的强度即增加,14 d时达高峰,28 d时稍有下降。UUO治疗组AT1、JAK2、STAT3蛋白表达的上调趋势明显受到抑制,与UUO未治疗组比较差异均有统计学意义(均P<0.01),但其表达仍强于对照组(均P<0.05)。UUO未治疗组三种蛋白表达两两之间的相关系数r值均大于0,且呈高度正相关关系(均P<0.01)。结论UUO大鼠模型肾小管间质损伤早期,AngⅡ/AT1R/JAK2/STAT3间可能存在一条促肾小管间质损伤的信号途径;给予苯那普利和氯沙坦治疗可明显抑制该信号途径的激活。Objective To investigate the tendency of JAK2/STAT3 protein expression mediated by angiotensin type 1 receptor in early stage of tubulointerstitial lesions in rats,and to explore the effects of benazepril and losartan. Methods Seventy-two 3-week-old male Wistar rats were randomly divided into three groups： UUO group（ n = 24）, UUO ＋ ACEI ＋ ARB group（ n = 24） and control group（n = 24）. The unilateral ureteral obstruetion（UUO） was used to establish the experimental model. At day 3,7, 14,28 after treatment, the expression of AT1 R, JAK2,STAT3 proteins in renal tissues were detected by immunohistochemical methods： The correlations among AT1R,JAK2 and STAT3 protein expression were analyzed at different time points. Results Compared with control group,the expression of AT1R,JAK2,STAT3 proteins increased at day 3 in UUO group,peaked at day 14,and slightly decreased at day 28. The expression of 3 proteins was inhibited in UUO＋ ACEI ＋ ARB group（P 〈 0.01） ,but still higher than in control group（ P 〈 0.05）. Positive correlations were observed among the expression of three proteins（P 〈 0.01）. Conclusion There might be a biologic signal pathway among Ang Ⅱ ,AT1R,JAK2 and STAT3 in the early phase of tubulointerstitial lesions induced by unilateral ureteral obstruction in rats. Benazepril and losartan could inhibit the activation of the signal pathway.

关 键 词：肾小管间质纤维化 单侧输尿管梗阻 JAK2 STAT3 血管紧张素Ⅱ1型受体 

分 类 号：R692.6[医药卫生—泌尿科学]