Effect Of Grape Seed Procyanidins On The Renal Structure And Excretion Of Urine Function In Spontaneously Hypertensive Rats

Objective: To study the effect of grape seed procyanidins(GSP) on the renal structure and excretion of urine function in spontaneously hypertensive rats(SHR) and to explore its possible mechanism.Methods: 24 male SHRs(8-week-old) were randomly divided into SHR group(SHR), low dose GSP group(GSP-low), high dose GSP group(GSP-high) and captopril used for positive control group(captopril), 6 Wistar Kyoto rats(8-week-old) were randomly served as negative control group(control) after one week adaptation with general meals and diet balance. According to the experimental group, the rats were administered intragastrically with saline, grape seed procyanidins(50mg/kg/d or 200mg/kg/d) or captopril for 6 weeks, respectively. Tail systolic pressure(SBP) of the rats was measured by tail culf method once two weeks. After 6 weeks of treatment, 24 h urinary protein, retinol binding protein(RBP) and alpha 1 microglobulin(α1-MG) contents were examined after collected 24 h urine of rats with metabolic cage. The blood urea nitrogen(BUN), serum creatinine(SCr) and cystatin C(Cys C) levels in blood serum of eyeball were measured. Removing the bilateral kidney, gross morphology of the kidney was observed by naked eye, the body weight, left and right kidney weight of rats were weighed to calculate the renal mass index(RMI). The morphological changes and the contents of collagen, MT/LD of renal small artery, glomerular collagen deposition score(GCDS) and tubular interstitial disease score(TIDS) were observed or were calculated by HE staining and Masson staining. Superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) activity, total antioxidant capacity(T-AOC) and malondiadehyde(MDA) in left renal cortex were measured. The expression of extracelluar signal-regulated kinase 1/2(ERK1/2) and phosphorylated extracelluar signal-regulated kinase 1/2(p-ERK1/2) in renal cortex were detected by western blot analysis.Results: After 6 weeks of treatment, compared with control group, the SBP in 2w, 4w and 6w, 24 h urinary protein, RBP and α1-MG contents in urine, BUN, SCr and Cys C in blood serum, collagen content in renal tissue, MT/LD of renal small artery, GCDS and TIDS, MDA content and the expression of ERK1/2 and p-ERK1/2 in left renal cortex were significantly increased in SHR group(P<0.01, P<0.05), but SOD and GSH-Px activity and T-AOC in left renal cortex were markedly decreased in SHR group(P<0.05, P<0.01). Gross morphology of bilateral kidney is basically normal, RWI of left and right kidney were raised(P>0.05), pathological changes of glomerular, renal interstitial and renal tubules were observed. Compared with SHR group, administering with GSP could significantly decrease SBP in 2w, 4w and 6w, 24 h urinary protein, RBP and α1-MG contents in urine, BUN, SCr and Cys C in blood serum(P<0.01, P<0.05), RWI(P>0.05), collagen content in renal tissue, MT/LD of renal small artery, GCDS and TIDS, MDA content and the expression of ERK1/2 and p-ERK1/2 in left renal cortex(P<0.05, P<0.01), increase SOD and GSH-Px activity and T-AOC in left renal cortex(P<0.01), improve the renal pathological injury caused by hypertension, especially in high dose GSP group(P<0.01). GSP exerted protective effects which were similar to those of captopril, a clinically approved cardiac protective agent(P>0.05).Conclusion: These data suggest that GSP may protect the kidney from injury in structure and excretion of urine function through lowering the SBP, improving antioxidative stress ability of SHRs and decreasing the expression of ERK1/2 and p-ERK1/2 in renal tissue.