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Background and objective Renal fibrosis is the common pathway of kidney diseases progressed to end-stage renal disease(ESRD). Renal fibrosis is characterized by the accumulation of extracellular matrix (ECM) components including collagen types I, IV, as well as fibronectin. Recently study evidences demonstrated that myofibroblast play a major role in the development and progression of renal fibrosis, and that to inhibit the myofibroblast biological function can effectively retard the progress of renal fibrosis. RPM is a new, potent immunosuppressive agent, it possesses a variety of pharmacological effects, including anti-inflammation, anti-virus, anti-proliferation and protecting vascular. Some research has shown that RPM has benefical effects on focal segmental glomerulosclerosis. RLX is a selective estrogen receptor modulator, ameliorated albuminuria, reduced mesangial expansion and accumulation of extracelluar matrix in diabetic nephropathy . The purpose of the present study was to dynamically observe myofibroblast by investigate the expression ofα-smooth muscle actin(α-SMA), and to explore the relationship with development of proteinuria and chronic renal fibrosis. Forthermore to study the renoprotective effects or not of rapamycin and raloxifene in chronic proteinuria renal fibrosis rats and to explore the possible mechanism of it’s pharmacologic effects.Methods ninety-six male Sprague-Dawley(SD) rats were diveded into four groups at random. Control group (group A, n=24), model group (group B,n=24), model group treated with RPM (group C, n=16), model group treated with RLX (group D, n=32). Chronic proteinuric Proteinuric model was induced by a single does of adriamycin equal to 4 mg/kg and twice injected intravenously at an interval of a week afterwad, group C and group D was given rapamycin 1.5 mg/kg, raloxifene 3.0 mg/kg daily intragastric administration individually after 2 weeks later of the first injectiong of adriamycin. Sample of group A, group B and group D were collected at the end of 4th, 7th, 10th and 13th week respectively. At the end of 7th week, samples of group C were collected. Urine protein excretion was evaluated at the end of 4th, 7th, 10th, 13th week after the first injection of adriamycin. Renal pathological changes were examined by HE, PAS and Masson staining, the expression ofα-smooth muscle actin(α-SMA),fibronectin(FN) were determined by Immunohistochemistry.Results 1. 24 h Urinary protein excretion At the end of 4th, 7th, 10th, 13th week, 24 h Urinary protein excretion were significantly increase in group B, D compared with group A at the same time (P<0.01), and at the end of 7th, group C compared with group A showed similar tendency(P<0.01). They rose further as the disease-process progressed(P < 0.01). 24 h Urinary protein excretion in group C and D were significantly lower than that in group B in crossponding time(P<0.01).2. Renal pathologic morphology Lightscope observation showed that focal segmental glomerulosclerosis, glomeruli hypertrophy, Bowman’s capsule expansion were found in group B at the end of 7th week. At the end of 13th week glomerulosclerosis and tubulointerstitium fibrosis were extensive. Compared with group B at the end of 10th week, glomerulosclerosis and tubulointerstitium fibrosis of group D were markedly attenuated, Tubulointerstitium injury index (TII) was markedly lower (P<0.05).3.α-SMA, FN protein expression in renal tissue immunohistohemistrical staining method noted that the expression ofα-SMA was markly increased at the end of 4th week in group B, with the development of disease-process, were obviously increased(P<0.05). Group C and D were significantly lower than that in group B in crossponding time(P<0.05). Expression of FN showed similar tendency((P<0.05). Conclusion In the model of chronic proteinuria renal fibrosis, rapamycin and raloxifene had benefical effects on reduction of renal fibrosis, and this effect may be associated with inhibition of myofibroblast biological function.
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