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The Experimental Study Of Renoprotective Effect Of ShenHua On Rats With 5/6 Nephrectomy

Posted on:2006-04-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:J J LiFull Text:PDF
GTID:1104360152494758Subject:Internal Medicine
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Background and Objective : Almost all forms of kidney diseases progressing to end-stage renal failure are characterized by diffuse glomerular sclerosis and interstital fibrosis. Whatever the initial injury, the remaining nephrons undergo adaptive hypertrophy and hyperfiltration that minimize the functional consequences of the progressive nephron loss. However, the adaptation ultimately leads to a vicious cycle in which hyperfiltration of the remaining nephrons impairs glomerular barrier, which in turn induces tubulointerstitial damage and then results in the loss of more nephrons. Both angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) are shown to break the vicious cycle and protect kidneys from progressive injury. In recent years, more attention has been focused on the inflammatory infiltration present in various types of progressive renal diseases in humans and in experimental models. The number of inflammatory cells in the renal interstitium closely correlates with the severity of glomerular and tubulointerstitial lesions and with loss of renal function.Inflammatory cells and activated intrinsic kidney cells can produce various cytokines, which can promote the progress of glomerular sclerosis and interstital fibrosis .So it may be a novel therapy for chronic renal disease through reducing the infiltration of inflammatory cells. ShenHua is a Chinese formulated product designed to chronic nephritis, comprise of many immunoregulation herbs.Our previous results showed that ShenHua can inhibit the inflammation, proliferation of Mesangial cells and accumulation of extracellular matrix in serum-disease rat model. So, wehypothesized that ShenHua can slow down the progression of CKD by inhibiting the infiltration of inflammation cell and the expression of cytokine. To test this hypothesis, we first used the rat model of 5/6 subtotal nephrectomy to study the in vivo effects of ShenHua on renal function, pathology. Second we probe the expression of proinflammatory and profibrogenic cytokine to study the possible mechanisms for the renoprotective effect of ShenHuaMaterials and Methods: Male Wistar rats were subject to 5/6 renal ablation by two-step operation and the 50 survival rats were randomly were randomly assigned to 5 groups: untreated, Irbesartan treated (20mg/kg/d), three dosage ShenHua treated (2, 1, 0.5 g/kg/d). Sham-operated rats severed as controls. Distilled water or medicine was administrated respectively by gavage during the period of 12 weeks. The general status, body weight, systolic blood pressure, proteinuria, serum creatinine ( Scr) , serum total protein, serum albumin, triglyceride, cholesterol and the weight of remnant kidney were measured. Glomerular and tubulointerstitial histological damage scores were also measured. Additionally, we detected the protein and/or mRNA expression of ED-1, proliferating cell nuclear antigen (PCNA) ,a-smooth muscle actin (a-SMA), mononuclear macrophage migration inhibitory factor (MIF), transforming growth factor-pi (TGFPi), fibroblast growth factor-2 (FGF-2), connective tissue growth factor (CTGF) and collagen-1 (COL-I) in sham operation group, model control and secondary ShenHua group by immunohistochemistry, Western blotting and Northern blotting.Results: Compared to untreated group, ShenHua treated groups showed significantly smaller scores of glomerular( 0.49±0.11 vs. 0.19±0.08, P<0.05 ) and tubulointerstitial histological damage ( 0.63±0.37 vs. 1.26±0.58, PO.05 ) at 12th week. The plasma albumin were higher (30.43±3.57 g.L"1 vs. 22.17±3.78 g.L"1 P<0.05 ), while 24hUP( 68.18±14.99 mg/24h vs.120.47±45.13 mg/24h, P<0.01), serum cholesterol, creatinine ( 67±5.90 umol/L vs. 193.44±106.78 umol/L, P<0.05), mean section area and glomerulus's volume [ (1.70 ±0.07) * 106um3 vs.
Keywords/Search Tags:ShenHua tablet, experimental study, 5/6 nephrectomy, rats
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