| Background and objective Diabetic nephropathy (DN) has become one of the main cause of end-stage renal disease (ESRD), but unfortunately the intimate mechanisms leading to the development and progression of renal injury are not yet fully known. Oxidative stress and inflammation are relevant factors in the pathogenesis of diabetes. Moreover, different inflammatory molecules, including chemokines, adhesion molecules, and proinflammatory cytokines, may be critical factors in the development of microvascular diabetic complications, including nephropathy. The recent study in vivo and in vitro evidence demonstrated that antioxidant and anti-inflammatory treatment have significant protective effects on DN. Total glucosides of paeony(TGP) are active compounds extracted from the roots of the tradition herb Paeonia lactiflora Pall. It possesses a variety of pharmacological functions, include anti-inflammation, anti-oxidative stress, anti-hyperlipidemic, liver protection and renoprotection. The purpose of the present study was to investigate the possible renoprotective effects of TGP in early diabetic rats induced by STZ. Methods Fifty adult male Sprague-Dawley rats were separated into five groups at random. Control group( n=10), model group( n=10), model group treated with TGP(50 mg?kg-1, by gavage, n= 10), model group treated with TGP(100 mg·kg-1, n= 10) and model group treated with TGP(200 mg·kg-1, n= 10). To induce an experimental model of diabetes, rats received a single intraperitoneal injection of STZ (60mg·kg -1.d-1). TGP was given by gavage. Eight weeks after STZ injection, the following determinations were done in samples: (1) BG were determined according to standard methods; (2) renal tissue MDA were determined by spectrophotometric method, 24 hours AER were measured by enzyme immunoassay (EIA); (3) Renal lesions were evaluated using PAS staining, the mean glomerular volume (VG) and indices for tubulointerstitial injury ( TII) were measured by using pathology image analysis system software; (4) Western-blotting for renal intercellular adhesion molecule-1( ICAM-1) and 1α(IV) collagen protein were quantified densitometrically, and immunohistochemistry for transforming growth factorβ1(TGFβ1) was performed by streptavidin-biotin complex (SABC) technique. Results 1 BG, Body weight (BW) ratio of KW to BW (KW/BW), AER, liver function: 8 weeks after STZ injection, there was a significant increase in BG (P<0.01) and significantly decreased in BW (p<0.01) in diabetic rats compared with control group. The BG level of TGP group(50 mg,100 mg and 200mg·kg-1) have no statistically significant difference compared with model group. KW/BW in TGP group (50 mg,100 mg and 200mg·kg-1) was decreased compared with model group, but there have no statistically significant. AER in model group were significantly higher than control group, and AER in TGP group(50 mg,100 mg and 200mg·kg-1) were significantly lower than model group(P<0.05, P <0.01). TC and TG in model group was markedly increased compared with control group, and TC and TG in TGP group(50, 100, 200 mg·kg-1) have no statistically significant difference compared with control group. In addition, ALT and AST have no difference between control group, model group, and TGP group(50, 100, 200 mg·kg-1). It shows that TGP have no effect on liver function. 2. Renal pathologic morphology: Compared with control group, VG and TII in model group was significantly increased. VG in TGP group(50 mg·kg-1) was significantly lower than model group(P<0.05),TII in TGP group(50 mg·kg-1) was lower than model group, but there have no statistically significant. VG and TII in TGP group(100, 200 mg·kg-1) was significantly lower than model group(P<0.05, P<0.01). 3.MDA level in renal tissue: MDA in model group was significantly higher than control group; The MDA level of TGP group(50,100 mg·kg-1)have no statistically significant difference between compared with model group. MDA in TGP group(200 mg·kg-1)was significantly lower than model group(P<0.05). 4. 1α(IV) collagen protein expression in renal tissue Western blot analysis noted that an increase in the amount of immunoreactive peptide was seen in kidney for group DM rats compared to that from group C rats. Densitometric analysis of the Western blot showed a 2.7 fold increase in the amount of 1α(IV) collagen protein from model group rats with respect to control group rats, TGP treatment(50, 100, 200 mg·kg-1) could reduced 1α(IV) collagen protein expression by approximately 47.9 %,60.4 % and 72.9 %,repectively. 5. ICAM-1 and TGFβ1 expression in renal tissue Western blot showed a 3.9 fold increase in the amount of ICAM-1 protein from model group rats with respect to control group rats,TGP treatment (50, 100, 200 mg·kg-1)could reduced 1α(IV) collagen protein expression by approximately 39.2 %,72.7 % and 83.8 %,repectively. In the kidneys of group C, there was minimal immunohistohemistrical staining for TGFβ1 in glomeruli and tubulointerstitium of control group rats. Immunostaining for TGFβ1 was markedly increased in model group in glomeruli and tubulointerstitium.,TGFβ1 expression in TGP group(50 mg·kg-1)was lower than model group, but it didn't have statistically significant. TGFβ1 expression in TGP group(50, 100, 200 mg·kg-1)were significant decreased compared with model group. Conclusion Renoprotective mechanism of TGP may be involved to inhibitory effect on the expression of ICAM-1 and TGFβ1 in diabetic rats. |
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