氯吡格雷联合伊贝沙坦对5/6肾切除大鼠肾脏的保护作用

Combined Clopidogrel and Irbesartan Therapy Attenuated the Renal Disease Progression in Rats with 5/6 Nephrectomy

目的:观察氯吡格雷联合伊贝沙坦对5/6肾切除大鼠肾脏的保护作用,并比较联合用药是否比单独用药效果更好。方法:雄性Wistar大鼠随机分为5组:假手术组(SHM)、模型对照组(NX)、氯吡格雷治疗组(CLO)、伊贝沙坦治疗组(IRB)和氯吡格雷联合伊贝沙坦治疗组(CLO/IRB),每组12只。氯吡格雷按20mg·kg-1·d-1给药,伊贝沙坦按20mg·kg-1·d-1给药,氯吡格雷联合伊贝沙坦给药(氯吡格雷按20mg·kg-1·d-1加伊贝沙坦按20mg·kg-1·d-1),每天8∶30开始灌胃给药;假手术组和模型对照组给予相应量的蒸馏水。分别观察治疗4周末和8周末大鼠的血压、尿蛋白、血生化以及肾脏病理改变。结果:治疗8周末,与模型对照组比较,氯吡格雷/伊贝沙坦可以显著改善大鼠的一般情况,降低24h尿蛋白排泄量和血肌酐水平(P<0.05),减轻肾小球硬化及肾小管间质病变,降低平均肾小球截面积。伊贝沙坦降尿蛋白作用比氯吡格雷强。氯吡格雷联合伊贝沙坦降尿蛋白、血清肌酐、减轻肾脏病理损害作用比单独用药效果好。结论:氯吡格雷/伊贝沙坦可以减轻肾小球硬化和肾小管间质病变,减少尿蛋白排泄,延缓大鼠慢性肾衰竭的进程;联合用药比单独用药效果更为有效。

Objective： To observe combined Clopidogrel and lrbesartan therapy attenuated the renal disease progression in rats with 5/6 nephrectomy, Meanwhile, we compared the effects of combining CLO with IRB, versus either drug alone on the renal disease progression in this rat model. Methods： Male Wistar rats were randomly assigncd to 5 groups： Sham operation group （SHM）, untreated group （NX group）, elopidogrel treated group （CLO group, 20 mg·kg^-1·d^-1）, irbessartan treated group （IRB group, 20 mg·kg^-1·d^-1）, and clopidogrel plus irbesartan treated group （CLO/IRB group, 20 mg·kg^-1·d^-1 plus 20 mg·kg^-1·d^-1 ）. Distilled water or medicine was administrated respectively by gavage during the period of 8 weeks. The general status, body weight, systolic blood pressure, proteinuria （24 hUP） and serum creatininc （Ser） were measured. Glomerular and tubulointerstitial histological damage scores were also measured. Results： At the end of 8 week treatment, Compared to NX group, CLO group or IRB group reduced 24 hUP and Scr. Compared to NX group, CLO/IRB treated group showed significantly smaller scores of glomerular .sclerotic index and tubulointerstitial histological damage. The mean glomerular sectional area （AG） was also lower than that in the NX group. Conclusion： CLO/IRB can inhibit the compensatory hyperplasia and slow the progression of chronic renal injury. Compared to single clopidogrel or irbesartan, combination therapy was more effective in attenuating renal damage.