高盐诱导的自发性高血压大鼠肾脏损害与外周血单核细胞亚群变化的相关性

Correlation between peripheral blood monocyte subsets and renal injury in high-salt fed spontaneously hypertensive rats

  • 摘要: 目的探讨高盐诱导的自发性高血压大鼠(SHR)肾脏损害与外周血单核细胞亚群变化的相关性。方法7周龄雄性SHR按饲料中的NaCl浓度随机分为低盐(0.5%NaCl)组和高盐(8%NaCl)组,干预12周。所有大鼠以标准的尾压法测定血压,分别在喂食干预前及干预末采血,利用流式细胞术分析单核细胞亚群的变化;干预末留取血和尿样本进行血、尿肌酐及尿微量白蛋白(MA)的测定;利用血氧水平依赖磁共振成像(BOLD-MRI)评估肾脏组织的氧合状态;以苦味酸-天狼猩红染色观察肾脏纤维化程度;最后分析检测指标与单核细胞亚群比例的相关性。结果干预结束时,高盐组尿量、心率及收缩压高于低盐组,体质量低于低盐组(均P<0.05);与低盐组比较,高盐组在高盐干预12周时CD43++单核细胞比例明显增加(8.80±1.69)%比(1.20±1.08)%,CD43+单核细胞比例明显减低(8.58±1.05)%比(14.89±1.72)%,均P<0.05。BOLD-MRI结果显示高盐组肾脏髓质R2*(反映组织缺氧程度)显著高于低盐组(P<0.05),而皮质虽有增高趋势,但结果无统计学意义(P>0.05);天狼猩红染色结果显示高盐组肾脏髓质纤维化程度明显增加,而皮质两组比较差异无统计学意义(P>0.05);并且肾脏髓质R2*与肾脏髓质纤维化呈正相关(r=0.701,P<0.05)。高盐组血肌酐、血肌酐与尿肌酐比值及尿MA高于低盐组,尿肌酐低于低盐组(P<0.05)。相关性分析结果显示干预结束时CD43++单核细胞比例与收缩压、髓质R2*、肾脏皮髓质纤维化、血肌酐、血肌酐与尿肌酐比值及尿MA呈正相关,与尿肌酐呈负相关(r分别为0.638、0.867、0.737、0.680、0.837、0.712、0.756及-0.700,均P<0.05)。结论高盐干预12周SHR外周血CD43++单核细胞比例明显增加,这一变化与肾脏缺氧、纤维化及肾脏损害程度相关。

     

    Abstract: Objective To explore the relationship between peripheral blood monocyte(PBM)subsets and renal injury(RI)in high-salt diet fed spontaneous hypertensive rats(SHR). Methods Seven-week-old male SHR were randomized to receive 0.5% NaCl diet(low salt,LS group)or 8% NaCl diet(high salt,HS group)for 12 weeks.Blood pressure was measured by tail cuff method. Peripheral blood were collected for flow cytometry analysis at baseline and after 12-week salt intervention. Blood and urine samples were collected for creatinine and microalbumin(MA)determination. At the end of intervention,all rats were anesthetized for blood oxygen level-dependent magnetic resonance imaging(BOLD-MRI)measurements. Picro-sirius red(PSR)staining was performed at time of sacrifice. The relationship between PBM subsets and RI was analyzed. Results Compared with LS group,the urine volume,heart rates and systolic blood pressure(SBP)of HS group were significantly increased while body weight was markedly decreased at the end of intervention(P<0.05). Flow cytometry analysis showed that the percentage of CD43++monocyte in HS group was apparently increased(8.80±1.69)% vs(1.20±1.08)%while a reduction of CD43+monocytes was observed compared with LS group (8.58±1.05)% vs(14.89±1.72)%,both P<0.05.BOLD-MRI measurements demonstrated that the R2*(reflect the degree of hypoxia)of renal medulla but not cortex was significantly increased(P<0.05). Moreover,PSR staining showed that a severe fibrosis was also found in renal medulla but not cortex of HS group. Meanwhile,renal medulla R2*was positive correlated with medulla fibrosis. Blood creatinine,the ratio of blood creatinine to urine creatinine,and the urine MA were all significantly increased while urine creatinine was markedly decreased at the end of intervention(P<0.05). A positive correlation between the percentage of CD43++monocyte and SBP,renal medulla R2*,renal fibrosis,blood creatinine,the ratio of blood creatinine to urine creatinine,and the MA and a negative correlation between the percentage of CD43++monocyte and urine creatinine were also observed. Conclusion The ratio of CD43++mononuclear cells in peripheral blood of SHR was increased significantly after 12 weeks of high salt intervention,and this change was related to renal hypoxia,fibrosis and RI.

     

/

返回文章
返回