罗格列酮改善肾大部切除大鼠左心室肥厚

The Effects of Rosiglitazone on Left Ventricular Hypertrophy in 5/6 Nephrectomized Rats

目的观察罗格列酮对肾大部切除大鼠左心室肥厚的影响。方法将大鼠随机分为假手术组、肾大部切除组、小剂量罗格列酮组[肾大部切除加5 mg/(kg.d)罗格列酮治疗]和大剂量罗格列酮组[肾大部切除加15mg/(kg.d)罗格列酮治疗]。8周后观察大鼠血压、尿蛋白、血尿素氮、血肌酐,并用放射免疫法测定血清血管紧张素Ⅱ、内皮素,测量大鼠左心室质量/体重,天狼星红染色测量心肌胶原纤维含量。结果罗格列酮能降低肾大部切除大鼠血压(P<0.01)、尿蛋白、血尿素氮和血肌酐(P<0.01或0.05)。与肾大部切除组比较,罗格列酮治疗组血清血管紧张素Ⅱ、内皮素均明显降低,差异有显著性(P<0.05)。与假手术组相比,肾大部切除组大鼠左心室质量/体重明显升高(P<0.05),罗格列酮治疗组大鼠左心室质量/体重较肾大部切除组有所降低,以大剂量罗格列酮组为明显(P<0.01)。肾大部切除组可见心肌组织大量胶原纤维沉积,用药后病变减轻,其中大剂量罗格列酮组心肌组织胶原纤维沉积明显减少(P<0.01)。结论罗格列酮可降低肾大部切除大鼠的血压;降低尿蛋白和改善肾功能;并可能通过降低血清血管紧张素Ⅱ、内皮素水平改善大鼠左心室肥厚。

Aim To investigate the effects of rosiglitazone on left ventricular hypertrophy in 5/6 nephrectomized rats. Methods Chronic renal failure of rats was induced by 5/6 nephrectomy.Then the inhibiting development of left ventricular hypertrophy（LVH） mechanism of the rats was explored by observing the nephrectomized rats which were randomly allocated into four groups： XL group（rosiglitazone treatment,5 mg/（kg·d））,DL group（rosiglitazone treatment,15 mg/（kg·d））,model group and sham group,in which the rats with sham operation served as control.5 mg/kg rosiglitazone,15 mg/kg rosiglitazone were respectively delivered daily via gavage for a period of eight weeks.The urinary protein,blood urea nitrogen（BUN）,serum creatinine（Scr）,blood pressure（BP）,angiotensin Ⅱ（AngⅡ）,endothelin（ET）,body weight（BW）,left ventricular weight（LVW） and LVW/BW were measured at the end of the study.Left ventricular hypertrophy was accessed by pathological analysis,and myocardium collagen fibers were stained with Picric acid-Sirius red. Results Compared with model group,the blood pressure of rats in XL group and DL group substantially decreased（P0.01）.So was the case with 24 hours urinary protein,Scr,BUN and plasma AngⅡ,ET.Compared with sham group,the ratio of left ventricle weight to body weight as well as collagen expressions of the left ventricular myocardium in the model group significantly increased（P0.05）.Compared with model group,the above parameters in DL group significantly decreased（P0.01）. Conclusion Rosiglitazone can obviously lower the blood pressure,reduce 24 hours urinary protein,BUN,Scr and recover renal historical damage,regress left ventricular hypertrophy,attenuate remodeling of myocardial collagen network in rats with chronic renal failure.The effect of rosiglitazone is possibly mediated by AngⅡ and ET.