The Renoprotectiveeffectsand Mechanisms Ofshen Shuai Bao Shen Capsule On Chronicrenal Failure Rats

Objective: To discuss the protective effect and mechanism of chronicrenal failure of Shenshuaibaoshen Capsule in 5/6 nephrectomy rat model, toinvestigate morphological changes in the kidney and renal function, tostudy the effects on proliferation apoptosis and mitochondrial apoptoticsignaling pathways in subtotally nephrectomized rats.Methods: By established a model of subtotal (5/6) nephrectomy and bytaken Shenshuaibaoshen Capsule for 12 weeks. The rats were assignedintothreegroups. Sham-operated(K)group.Model(M)group. ShenshuaibaoshenCapsule (S)group. The levels of renal function and urinary protein, the ratesof renal and body weigh and the changes of renal pathology by lightmicroscope were observed. The changes of Proliferating cell nuclerantigen(PCNA)and the protein level of CytC and caspase-3,caspase-9 were detected by immunohistochemical method. The mRNA ofcaspase-3, caspase-9 were detecte by real-time quantitative PCR andapoptotic cells by terminal deoxynucleotidyl transferase-mediated dUTPnick end labeling(TUNEL) at four different periods of time in 12 weeks (at2nd, 4th, 8th, 12th) after operation.Results: The levels of plasma creatinine and blood urea nitrogen and24h urinary protein excretion were elevated at 2nd week .The pathologicalchanges of the kidney in M group included swollen glomeruli, slightproliferation of mesangial cells and slight dilation of renal tubule; Focalsegmental glomerularsclerosis and renal fibrosis occurred at 12th week. Theindexs and rate of proliferation and apoptosis were higher in the tissues ofremnant kidney in M group than that in K group. The M group comparedwith the K group, the expression of CytC were increased in remnant kidney,the changes of mRNA and protein level of caspase-3,-9 had the sametendency and up-regulated wavily in the rat model. The S group comparedwith the M group, The renal function partly ameliorated, urinary protein excretion predominantly reduced and the appearance of renal failureretarded, pathological damages reduced. The indexs proliferation ofglomerulus and tubules cells before 8 weeks and apoptosis of glomerulusand tubules cells at 12week were reduced, the indexs proliferation ofinterstitial cells were inhibited and the apoptotic were promoted at the sametime, the proliferation and apoptosis rate of glomerulus and tubules before 8weeks were decreased and it were increased at 12 week, the proliferationand apoptosis rate of interstitial cells were decreasd. Compared with Mgroup the expression of CytC in S group were weakened, the increaseddegree of caspase-3,-9 were reduced.Conclusion: Shenshuaibaoshen Capsule can protect renal function andmorphological change in the kidney, The main roles of ShenshuaibaoshenCapsule ajusted the balance between proliferation and apoptosis in thetissues of remnant kidney,with the method of reducing the proliferation ofglomerulus and tubules cells before 8 weeks and apoptosis of glomerulusand tubules cells at 12 week, inhibiting the proliferation and promoting theapoptotic in interstitial cells at the same time, with the method ofdecreasing the proliferation and apoptosis rate of glomerulus and tubulesbefore 8 weeks and increasing it at 12 week, decreasing the proliferationand apoptosis rate of interstitial cells.with the mitochondria signalpathways playing the primary role to protect kidney and delay CRF.