氯高铁血红素对慢性肾功能衰竭大鼠的血压影响及其机制探讨

目的研究氯高铁血红素对慢性肾衰竭大鼠血压的影响,并探讨其可能机制.方法用5/6肾切除法建立CRF模型,研究分为3组(1)假手术组(sham组)、(2)慢性肾衰组(CRF组)、(3)氯高铁血红素组(hemin组).观察术后第10周(即给药后第8周)各组血清尿素氮、肌酐、尿蛋白、血红蛋白及术后第4,6,8和10周血压等指标;免疫组化方法检测肾组织中血红素氧化酶-1(HO-1)的表达和分布;双波长分光光度法测量血浆内源性CO的水平;放免法检测肾组织和血浆中内皮素-1(ET-1)的含量.结果与CRF组相比,hemin组在术后第6,8和10周均出现显著的血压下降(P＜0.05).同时,在术后第10周hemin组比CRF组血肌酐、尿素氮、尿蛋白显著降低(P＜0.05),贫血明显改善(P＜0.05);肾组织中HO-1表达明显增加,血浆中内源性CO水平明显升高,肾组织和血浆中ET-1水平明显降低(P＜0.05).结论hemin组具有延缓慢性肾功能衰竭大鼠高血压的发生和发展作用,这种作用与hemin诱导肾脏HO-1表达、增加血浆CO浓度,降低肾组织和血浆中的ET-1水平有关.

Effect of hemin on nephrogenic hypertension of chronic renal failure rats

To study the effect of hemin on nephrogenic hypertension of chronic renal failure rats and its possible mechanism. 5/6 renal nephrectomized rats were randomly assigned to three groups: sham operation group, CRF group and hemin group. We measured serum creatinine, BUN, urinary protein, HGB at the 10th week and blood pressure at the 4th, 6th, 8th, 10th week after operation. Immunohistochemistry was used to examine the expression and distribution of HO-1 in the rat kidney. The two-wavelength spectrophotometry was used to measure endogenous carbon monoxide in plasma. Radioimmunoassay was used to examine the level of ET-1 in the kidney and plasm. Compared with CRF group, nephrogenic hypertension of hemin group was reduced significantly at the 6th, 8th, 10th week after operation, and followed with the decrease of serum creatinine, BUN, urinary protein and the improvement of nephrogenic anemia at the 10th week after operation. Hemin not only increased the expression of HO-1, reduced the expression of ET-1 in the kidney, but also increased the concentration of carbon monoxide, reduced the level of ET-1 in the plasm. Conclusion] Hemin can retard the occurrence and development of nephrogenic hypertension of chronic renal failure rats. This role has much to do with inducing the expression of HO-1 in the kidney, increasing the concentration of carbon monoxide in the plasm and reducing the level of ET-1 in the kidney and plasm.