| Background and Objective: Mesangial proliferative glomerulonephritis including Immunoglobulin A nephropathy (IgAN) is a common kidney disease in our country, vasculopathy is very common in chronic kidney disease and has been showed to be closely correlated to glomerular sclerosis and renal interstitial fibrosis, and play important role in the progression of chronic kidney disease. The degree of renal lesions could be reflected by vascular lesion and vascular lesion could decied the prognosis and direct the treatment. Up to now, no proper mesangial proliferative glomerulonephritis vasculopathy model could be used to study vasculopathy, if vasculopathy model similar to the human mesangial proliferative glomerulonephritis could be established, we could probe the mechanism and intervention method, screen medicines which could delay and treat mesangial proliferative glomerulonephritis vasculopathy. It has been shown high fat diet could induce arota artherosclerosis in rat. So We constructed rat model of progressive mesangial proliferative glomerulonephritis with OX7 antibody secretared by OX7 hybridoma cell, and induced vasculopathy by high fat diet in progressive mesangial proliferative glomerulonephritis model, eveniually Leflunomid was rendered, vasculopathy and the infiltration of inflammation cell and the expression of cytokine was observed.Materials and Methods: (1) Male Wistar rats were subject to one side renal ablation and the survival rats were randomly assigned to 3 groups: injected OX7 only one time, injected OX7 continuously, one side renal ablation rate severed as controls. One time injection group was injected OX7 (100mg/kg) through caudal vein 3 days after renal ablation, continuous injection 0X7 groupwas injected OX7 continuously(100mg/kg, one time per week, 4 times). The general status, body weight, systolic blood pressure, proteinuria, serum creatinine (Scr) , serum total protein, serum albumin, triglyceride, cholesterol were measured. Glomerular, tubulointerstitial and vascular histological damage scores were also measured.. (2) male Wistar rats were subject to one side renal ablation and the survival rats were randomly assigned to 4 groups: high fat diet group, nephritis group, nephritis fed with high fat diet group, one side renal ablation rats severed as controls. The method injecting OX7 was the same as the first part. Vitamin D3 was intraperitoneal injected to rats after the second day (600, 000u/kg, one time per 4 weeks )and fed with hgh fat diet, The general status, body weight, systolic blood pressure, proteinuria, serum creatinine, serum total protein, serum albumin, triglyceride, cholesterol and serum calcium were measured. Glomerular, tubulointerstitial and vascular histological damage scores were also measured. (3) male Wistar rats were subject to one side renal ablation and the survival rats were randomly assigned to 3 groups: nephritis fed with high fat diet group, Leflunomide treated group, one side renal ablation rats severed as controls. The method injecting OX7 , Vitamin D3 and fed with high fat diet was the same as the first part. Sodium Chloride or Leflunomide(2mg/kg/d) was administrated respectively by gavage during the period of 10 weeks. The general status, body weight, systolic blood pressure, proteinuria, serum creatinine, serum total protein, serum albumin, triglyceride, cholesterol, low density lipoprotein, high density lipoprotein and calcium were measured. Glomerular, tubulointerstitial and vascular histological damage scores were also measured. Additionally, we detected the expression of ED-1, monocyte chemoattractant protein (MCP-1), vascular cell adhesion factor(VCAM-1), a-smooth muscle actin (a-SMA) and heat shock protein 27(HSP27) by immunohistochemistry, western blot and RT-PCR.Results: (1) Progressive mesangial proliferative glomerulonephritis model was set up by one time injection OX7 and continuous injection OX7 on one side renal ablation rat, Segmented glomerulus sclerosis, renal tubular focus atrophy,decreased capillary number in renal interstitium, intrarenal arterial wall thickening were observed in continuous injection group at week 8, but the same pathological change were observed in one time injection group at week 16, scores of glomerular , tubulointerstitial and vascular histological damage in continuous injection group were significantly higher than (P<0.05 ) one time injection group.(2) At week 4, atherosclerotic plaques were seen in the aorta in nephritis loaded with high fat diet group, and at week 8, intrarenal arterial wall thickening were observed. At week 10, atherosclerotic plaques were seen in the aorta in high fat diet group, no plaques were seen in the aorta in nephritis group, intrarenal arterial wall slightly thickening was observed in nephritis and high fat diet group, scores of glomerular, tubulointerstitial and vascular histological damage in nephritis loaded with high fat diet group were significantly higher than (P<0.05 ) nephritis and high fat diet group.(3) Compared to nephritis loaded with high fat diet group, Leflunomide treated groups showed significantly lower scores of glomerular , tubulointerstitial and vascular histological damage(P<0.05 ) at week 10, the plasma albumin were higher, while arterial blood pressure, 24h urine protein, serum creatinine (P<0.05 ) were lower in the Leflunomide treated group, arota and intrarenal arterial lesion was lighter than nephritis loaded with high fat diet group, the number of ED-1 was decreased and the expression of MCP-1and VCAM-1 was down-regulated.Conclusion: Progressive mesangial proliferative glomerulonephritis model was set up by continuous injection OX7 on one side renal ablation rat, progressive mesangial proliferative glomerulonephritis vasculopathy model was set up by high fat diet on mesangial proliferative glomerulonephritis rat, and vasculopathy and chronic renal injury was extenuated by Leflunomide with inhibition of the inflammation infiltration and expression of cytokines in the remnant kidney.
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