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目的研究盐敏感性高血压大鼠肾损伤中巨噬细胞移动抑制因子(MIF)表达的变化及MIF抑制剂(ISO-1)对肾脏的保护作用。方法 40只健康雄性SD大鼠,行左肾摘除术后存活30只,随机分为3组:空白组8只,皮下注射等量的植物油,饮用自来水。其余用作造模:皮下注射醋酸去氧皮质酮(DOCA)油剂(30mg·kg-1·周-1),饮用1%Na Cl,0.2%KCl盐水,8周后取其中造模成功的大鼠16只,随机分为模型组和干预组,每组8只。第9周开始干预组以ISO-1 200μg/kg隔日皮下注射,模型组和空白组以等量的生理盐水皮下注射,持续4周。各组大鼠每周监测收缩压。于0、4、8、12周检测24 h尿蛋白定量。实验完成后处死大鼠,取右肾标本,做HE染色后观察肾脏组织病理改变,半定量分析肾小管的损伤程度。Western印迹法检测肾组织中MIF蛋白的表达。结果 12周时,与空白组比较,模型组的收缩压[(112.41±0.87)mm Hg vs(175.12±0.89)mm Hg],24 h尿蛋白量[(3.53±0.30)mg vs(19.66±0.48)mg],MIF的表达量[(0.0515±0.0005)vs(0.6525±0.0282)]明显增高(P均<0.05),肾脏尤其肾小管的病理损伤较空白组明显加重;与模型组比较,干预组的收缩压[(175.12±0.89)mm Hg vs(139.23±1.12)mm Hg],24 h尿蛋白量[(19.66±0.48)mg vs(7.71±0.84)mg],MIF的表达量[(0.6525±0.0282)vs(0.5564±0.0007)]明显降低(P均<0.05),肾脏尤其肾小管的病理损伤较模型组减轻。结论 MIF可能参与盐敏感性高血压大鼠肾脏损伤的过程,ISO-1可减轻MIF对肾脏的损伤,保护肾脏。
Objective To investigate the changes of macrophage migration inhibitory factor (MIF) expression and the protective effect of MIF inhibitor (ISO-1) on renal injury in salt-sensitive hypertensive rats. Methods Forty healthy male Sprague-Dawley rats were randomly divided into three groups: control group (n = 8) and subcutaneous injection of equal amount of vegetable oil and drinking tap water. The rest were used for modeling: subcutaneous injection of DOCA oil (30mg · kg-1 · week-1), 1% NaCl, 0.2% KCl saline, 8 weeks after successful modeling Sixteen rats were randomly divided into model group and intervention group, with 8 rats in each group. At week 9, the intervention group was subcutaneously injected with ISO-1 200 μg / kg every other day. The model group and the blank group were injected subcutaneously with normal saline for 4 weeks. Systolic pressure was monitored weekly in each group. 24 h urine protein was measured at 0, 4, 8 and 12 weeks. After the experiment was completed, rats were sacrificed and the right kidney specimens were taken. The pathological changes of the kidney tissues were observed after HE staining and the degree of renal tubule injury was analyzed semi-quantitatively. Western blotting was used to detect the expression of MIF protein in renal tissues. Results Compared with the blank group, systolic blood pressure ([112.41 ± 0.87] mm Hg vs (175.12 ± 0.89) mm Hg] and 24 h urine protein [(3.53 ± 0.30) mg vs (19.66 ± 0.48 ) mg], the expression of MIF was significantly higher than that of the blank group [(0.0515 ± 0.0005) vs (0.6525 ± 0.0282)] (P <0.05) (175.12 ± 0.89) mm Hg vs (139.23 ± 1.12) mm Hg], 24 h urinary protein level [(19.66 ± 0.48) mg vs (7.71 ± 0.84) mg], and the expression of MIF [(0.6525 ± 0.0282) vs (0.5564 ± 0.0007)] (P <0.05). The pathological changes of renal tubules, especially tubules, were alleviated compared with the model group. Conclusion MIF may be involved in the process of renal damage in salt-sensitive hypertensive rats. ISO-1 can reduce the damage of kidney and protect the kidneys of MIF.