| Objective:To study the expression of macrophage migration inhibitory factor(MIF) in the damaged renal tissue of rats with salt-sensitive hypertension and the relationship between MIF and kidney damage. Methods:40 healthy male SD rats, 30 rats survive after kidney excision.These were randomly divided into 3 groups: 16 rats as the experimental group,which were injected of hypodermic deoxycorticosterone acetate(DOCA) agent 30·g-1·week-1, drinking 1% Na Cl salt water,8 rats as the blank group which were subcutaneous injected of the same amount of vegetable oil, drinking tap water.After 8 weeks,select 16 successful rats as experimental group, which were randomly divided into model group and intervention group, each group of eight. The 8 rats of intervention group were injected of ISO-1 200ug·kg-1·day-1Subcutaneously, The model group and blank group were injected of the same amount of saline injection for 4 weeks. Monitor the systolic blood pressure of rats each week. At 0, 4th, 8th, 12 th weeks, Collect 24 hours urine to test 24 hours urinary protein quantitative with metabolic cage. Kill the rats after the experiment completed.Do the HE PAS and Masson staining to observe the pathological changes of the kidney tissue.Do semi-quantitative determination of renal damage degree. Detecting the quantity of MIF protein in renal tissue with Immunohistochemical and western blooting methods. Results:1. Blood pressure: Compared with the blank group, the systolic blood pressure of model group increased significantly at 4 weeks(p < 0.05), continuing to the end of the experiment, compared with model group, the systolic pressure of the intervention group decreased significantly at the twelve week(p< 0.05).2.24 h urine protein: The 24 h urinary protein quantity of the model grounp and intervention group were significantly larger than the blank group(p< 0.05)from the eighth week, continuing to the end of the experiment. After the intervention of ISO- 1, the quality of the 24 h urine protein of intervention group rats had a significant reduce in the twelve weekend compared with the model group(7.71 + /- 0.84 than 19.66 + /- 0.48, p< 0. 05).3.The pathological changes of renal tissue: glomerular of the blank group had no swelling, capillary loops was good, the renal tubular epithelial cells was complete, without any infiltration of inflammatory cells. The kidney tissues of model group rats had visible glomerular hyperplasia and mesangial cellular proliferation and narrowed renal capsule lumen. There were many swelling glomerular cells in the renal tissue of model grounp. The renal tubular epithelial cellular damaged area was larger. Part of the epithelial cells appearred grain-like changes. There were large amounts of inflammatory cells in the cavity.The tubule of individual rat had fibrosis modification, degree of pathological changes is given priority to mild-to-moderate.The kidney pathological change of intervention group was remiteed with different degrees. The swelling of glomerular was released, matrix hyperplasia was released, renal tubular cavity was reduced, the infiltration of interstitial inflammatory cell was less,the score of semi-quantitative analysis of renal tubular damage about the model group was higher significantly than the blank grounp(1.650 + /- 0.283,4.875 + /- 0.504)(p<0.05),the score of intervention group redused a lot than the model grounp(3.386 + /- 1.0223, 4.875 + /- 0.504)(p < 0.05).4.Immunohistochemical tochemical results:The expression of MIF protein was mainly in glomerulus and renal tubules, in which the expression of MIF protein was more obvious. The exoression of MIF protein in glomerular positive cells had no obvious difference in the three groups. The number of MIF protein in renal tubular was larger relatively than the glomerular cells. The number of MIF protein in model grounp was significantly larger compared with the blank group(p < 0.05).The number of MIF intervention group were decreased significantly than the model group(p< 0.05).5. Western Blot results: According to western blotting method to detect the quantity of MIF protein.The number of MIF protein in the blank group was few. The expression quantity in the model grounp increased obviously compared with blank grounp(p<0.05).The expression of MIF protein in the intervention grounp compared with model group decreased sigenificantly( p < 0.05). Conclusion:1. Chronic salt loading method could be successfully produced the model of saltsensitive hypertensive renal damage.2. MIF may participate in the development of salt sensitive hypertensive renal damage, including the fibrosis process of renal tubular.3.(ISO–1)MIF inhibitors can cut MIF expression in renal tissue, lower blood pressure, reduce proteinuria, reducing the pathological damage degree in model rats of salt sensitive hypertensive renal damage and it may be one of the effective methords to protect the renal function. |
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