The Renoprotect Effect Of Fps On Rats With Adriamycin-Induced Glomerulosclerosis

Objectives: Chronic kidney disese is a worldwide public health problem^[1]. Progressive glomerulosclerosis is the common pathologic pathway of various giomerular disease and prevention or delay of glomerulosclerosis has become the hot point of research in the field of kidney disease. So looking for safe drugs is of great significance. FPS is marine traditional Chinese drug. This study is going to investigate the effects and mechanism of fucoidan(FPS) on adriamycin-induced.Methods:1 Experimental animals Male SD rats (n=32),weighing 250-280g were randomized to divide into four groups: SHAM operative rats were group 1( SHAM group) (n=8) as contrast . Glomerulosclerosis rats models,made by unilateral nephrectomy plus adriamycin injection twice, were divided into group 2(Model Rats group, M group )(n=8 )as contrast model; group 3 as Benazepil group(B group)(n=8) and group 4 as FPS group(n=8). The B and FPS group were given Benazepil 4 mg·kg^-1 ang FPS 200 mg·kg^-1 by gavage for 8 weeks respectively, while SHAM and M group were given normal saline with equal volume by gavage at the same time. At 8 weekend, we collect the 24-hour urine of the rats from each group which were placed individually in metabolic cages, and arterial blood were obtain from heart .Then the rats were put to death and kidneys were obtained.2 Indices assayed: 24h Urinary protein quantitative, Scr, BUN, serum albumin,kindey morphology > glomerulosclerosis index and FN> Col IV> TGF-3i> TGF-Pi mRNA> PAI-1 mRNA expression in the kidney. Results:1 24-hour urinary protein quantitativeCompared with the M group untreated glomendosclerosis rats ,24-hour urinary protein quantitative of rats treated with fucoidan were significantly reduced (p<0.01). 24-hour uriany protein excretion of FPS group > B group and M group were higher than that of SHAM group. There was significant different among these groups (p<0.01).2 Blood creatinine, urea nitrogen and albuminBlood creatinine and urea nitrogen levels of FPS group ^ B group and M group were significantly higher than that of SHAM group (p<0.01) ; Compared with the M group ,serum creatinine and urea nitrogen levels of FPS groupB and group were significantly reduced (p<0.01). Compared with the SHAM group, albumin of FPS group^ B group and M group were significantly reduced (p<0.01), but there was not significamtly different among FPS group, B group and M group (p>0.05).3 kidney morphologyLight microscopic observation result showed that: 16% glomerulars had segmental glomerulosclerosis and 4% glomerulosclerosis in M group; In FPS group there were 9% glomeruluses have segmental glomerulosclerosis and 2% glomerulosclerosis. Glomerulus and capsular adhered was less than M group. The pathologic changes of B group is in accordance with the FPS group basically.4 Glomerulosclerosis index (GSI)The degree of GSI in FPS group^ B group> M group reduceded markedly than SHAM group (p<0.05). Compared with M group, GSI of FPS group > B group was significantly reduced (p<0.01).5 Expression of FN> Col IV\ TGF- P i in kidneyIn FPS group^ B group and M group, the expressions of FN> Col IV >. TGF- P i in kidney were significantly increased compared to SHAM group (PO.01). After treatment, all of the expressions of FPS group and B group were reduced, and there was significant different betwen FPS group and M group (p<0.01).6 RT-PCR showed fucoidan decreased the over-expressions of TGF- P i mRNA and PAI-1 mRNA in the kidney(p<0.01). Conclusion:1 24-hour urinary proteim BUN^ senurn creatinin Compared with the untreated glomerulosclerosis rats, 24-hour urinary protein quantitative -. BUNK serum creatinin of rats treated with Fucoidan were significantly reduced (p<0.01).2 FPS can reduced the lesion of renal tissue and the deposition of ECM in rats with adriamycin injection.3 FPS probably has some protecting effect on kidney of adriamycin-induced glomeulosclerosis rats by inhibiting the expression of TGF- 0 i and decreasing the synthesis of Col IV and FN.4 FPS could decrease the over-expression of TGF- P i mRNA fP PAI-1 mRNA expression in kidmey (p< 0.01).Measing: By this study we can know fucoidan conld decrease the urinary protein, BUN and serum creatinine extracellular matrix accumulation and TGF- p* i mRNA ^P PAI-1 mRNA over expression in kidney of rats . It can reduced the lesion of renal tissue. So,it may play important role in prevention and treatment of glomerulosclerosis.