自发性高血压大鼠纤维结合蛋白的表达及氯沙坦的干预作用

Effects of lorsartan on fibronectin's expression in spontaneously hypertensive rats

目的观察自发性高血压大鼠(SHR)血、尿纤维结合蛋白(fibronectin,Fn)水平、肾脏Fn的表达及氯沙坦的干预作用。方法雄性14周龄SHR 16只,随机分为高血压组(SHR组)和氯沙坦治疗组(T-SHR组),每组8只,T-SHR组氯沙坦灌胃30 mg/(kg.d);另选14周龄雄性Wistar-kyoto大鼠8只为正常对照组(WKY组)。16周后,观察各组大鼠体重、收缩压,双抗体夹心ELISA法检测血、尿Fn水平,免疫组化法检测肾脏Fn表达。结果①SHR组收缩压和尿Fn水平明显高于WKY组(P<0.05),血Fn水平明显低于WKY组(P<0.05),肾脏Fn主要表达于肾间质、部分肾小球系膜细胞和肾小球囊,其肾脏Fn表达明显高于WKY组(P<0.05);②T-SHR组收缩压及尿Fn水平较SHR组明显降低(P<0.05),血Fn水平较SHR组明显升高(P<0.05),肾脏Fn表达较SHR组明显降低(P<0.05)。结论 SHR尿Fn水平升高,血Fn水平降低,肾脏Fn表达水平上调;氯沙坦可能通过部分抑制SHR肾脏Fn的表达,对早期高血压肾损害有保护作用。

Objective To observe the effects of lorsartan on serum and urinary fibronectin（Fn） levels and the renal expression of Fn in spontaneously hypertensive rats（SHRs）.Methods Sixteen male 14 week-old SHRs were randomly divided into hypertensive group（SHR group） and losartan group（T-SHR group） administered by gastric lavage of losartan 30mg/（kg·d）,each group consisting of eight SHRs;eight male 14 week-old Wistar Kyoto rats served as negative control group（WKY group）.After 16 weeks,the weight and systolic pressure of rats in each group were observed.The serum and urinary Fn levels were measured by enzyme-linked immunoadsorbent assay（ELISA） and the renal expression of FN was determined by immunohistochemical analysis in different groups.Results ① The systolic pressure and urinary Fn level in SHR group were significantly higher than those in WKY group（P0.05）.The level of serum Fn was significantly lower in SHR group than in WKY group（P0.05）.The expression of Fn in renal tubulointerstitium,mesangial cells and Bownman＇s capsule increased greatly in SHR group compared with those in WKY group（P0.05）.② The systolic pressure and urinary Fn level in T-SHR group were significantly lower than those in SHR group（P0.05）.The level of serum Fn in T-SHR group was significantly higher than that in SHR group（P0.05）.The renal expression of Fn was significantly lower in T-SHR group than in SHR group（P0.05）.Conclusion The level of urinary Fn increased,that of serum Fn decreased and the renal expression of Fn increased.Lorsartan has protective effects on early hypertension-induced renal lesion by partly inhibiting the renal expression of Fn.