罗格列酮对高血压大鼠肾间质纤维化的影响及其机制

目的探讨罗格列酮改善高血压肾间质纤维化（RIF）的机制。方法高血压大鼠随机分为阳性对照组（2K1C组）和罗格列酮治疗组（RGL组）,另设假手术组（SHAM组）,比较三组大鼠的尾动脉收缩压（SBP）、尿β-微球蛋白（β2-MG）、血肌酐（SCr）、尿素氮（BUN）、肾组织纤维化半定量评分以及BMP7、CTGF的表达及肾脏病理改变。结果①治疗前,2K1C组及RGL组的SBP与尿β2-MG均较SHAM组明显增加。自第4周起,RGL组SBP和尿β2-MG较2K1C组也明显降低。②2K1C组及RGL组RIF程度较SHAM组明显加重,RGL组较2K1C组减轻。③与SHAM组比较,2K1C组及RGL组BMP-7表达减少,CTGF的表达显著增加。④RGL组较2K1C组BMP7表达升高,CTGF的表达减少。⑤BMP-7及CTGF与RIF程度分别呈负相关和正相关。结论罗格列酮可能通过上调高血压大鼠肾问质BMP-7的表达、下调CTGF的表达,发挥对肾脏的保护作用。

Effects and mechanism of rosiglitazone on the renal interstitial fibrosis of hypertensive rats

Objective To investigate the mechanism of rosiglitation improving renal interstitial fibrosis. Method Two-kidney one-clip models were established and randomly divided randomly into the positive control group（2K1C group） and the rosiglitazone-treated group（RGL group）. The shame rats were fed as the negative control group（sham group）. The blood pressure, the urine β2-MG, BUN and SCr,the pathological changes and the degree of fibrosis were compared among the three groups. The expression of BMP 7 and CTGF was detected. Result （1）The SBP and urine β2-MG heightened in 2klC group and RGL group compared with SHAM group, from the 4th week, the SBP and urine β2- MG decreased in RGL group compared with 2K1C group. （2）At 0 week, the contents of β2-MG markedly increased in 2K1C group and RGL group compared with the SHAM group,while there was no significant differences between 2K1C group and RGL group, there was no significant difference in the con tents of BUN and SCr among the three groups：At 10th week, the contents of β2-MG decreased significantly in RGL group compared with 2KIC group, there was also no difference in BUN and SCr. （3）The degree of renal interstitial fibrosis significantly aggravated in 2K1C group and RGL group compared with the SHAM group, while the degree of renal interstitial fibrosis alleviated in RGL group compared with the 2K1C group. （4）Compared with the SHAM group, the expression of BMP-7 decreased significantly in 2KIC group and RGL group, while compared with 2K1C group, the expression of BMP 7 increased in RGL group. （4）The expression of BMP-7 negatively correlated with the degree of fibrosis and CTGF respectively,the expression of CTGF and the contents of β2-MG positively correlated with the degree of fibrosis respectively, there was negatively correlated between the expression of BMP 7 and the contents of β2-MG. Conclusion Rosiglitazone may delay renal interstitial fibrosis and play a protective role on the kidneys by ul〉regulating the expression of BMP-7 in tubulointerstitium of hypertensive rats.