[Effect of shenshuning recipe on the extracellular matrix accumulation of the peritoneal fibrosis rats].

OBJECTIVE: To observe the effect of Shenshuning Recipe (SR) on the peritoneal function, accumulation of extracellular matrix (ECM), and the expression of transforming growth factor-beta1 (TGF-beta1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the peritoneal fibrosis rats. METHODS: The peritoneal fibrosis correlating peritoneal dialysis SD rat model was induced by injecting erythromycin and peritoneal dialysate. They were randomly divided into 4 groups according to body weight, i.e., the 1.50% peritoneal dialysate group (Group B), the 1.50% peritoneal dialysate + SR group (Group C), the 4.25% peritoneal dialysate group (Group D), and the 4.25% peritoneal dialysate +SR group (Group E), 15 in each group. Besides, another 15 rats was taken as the blank control group (n = 15, Group A). SR at the daily dose of 43.93 g/kg was given to rats in Group C and E by gastrogavage, while equal volume of normal saline was given to rats in other groups by gastrogavage. The changes of glucose in the peritoneal fluid were detected. The ultra filtration volume (UF)and mass transfer of glucose (MTG) were calculated. The pathomorphological changes of the peritoneum were observed. The distribution of collagen fiber, fibroblast count, collagen I (Col I), expressions of TIMP-1 and TGF-beta1 were determined. RESULTS: At the end of the 6th week, statistical difference was shown in UF [(-3.3 +/- 14.2) mL] and [(-2.0 +/- 10.7) mL], MTG [(18.1 +/- 0.8) mmol/kg] and [(16.1 +/- 1.2) mmol/kg], collagen fiber [(4 721.3 +/- 541.0)%] and [(6502.7 +/- 877.4)%], fibroblast [(0.087 +/- 0.010)/mm2] and [(0.131 +/- 0.042)/mm2], Col I [(187.5 +/- 36.9)%] and [(289.7 +/- 95.6)%], TIMP-1 [(2.57 +/- 0.94)%] and [(3.63 +/- 0.29)%], and TGF-beta1 [(104.0 +/- 20.7) ng/L] and [(108.2 +/- 17.5) ng/L] between Group C and Group E, when compared with the peritoneal dialysate group at the same concentration (P < 0.05, P < 0.01). CONCLUSION: SR could postpone the development of peritoneal fibrosis in peritoneal dialysis SD rats possibly through inhibiting expressions of TGF-beta1 and TIMP-1, and hindering the over-accumulation of ECM.

Optimized project of traditional Chinese medicine in treating chronic kidney disease stage 3: a multicenter double-blinded randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Stage 3 is the key phase of chronic kidney disease. Traditional Chinese medicine (TCM) has been used for the treatment of chronic kidney disease. But a large sample trial is desirable. MATERIALS AND METHODS: A total of 578 Chinese patients with primary glomerulonephritis in CKD stage 3 were randomly assigned to three groups: patients received TCM (TCM group), benazepril (Ben group), TCM combined with benazepril (TCM+Ben group). Patients were followed up for 24 weeks. The primary endpoint was the time to the composite of 50% increased of serum creatinine, end stage renal disease or death. RESULTS: eGFR in the TCM and the TCM+Ben group were improved (week 24 vs. baseline, P<0.05) while eGFR in the Ben group was decreased (week 24 vs. baseline, P>0.05). 24h urinary protein excretion (UP) and urinary albumin/creatinine (UAlb/Cr) were decreased in the TCM+Ben (week 24 vs. baseline, P<0.05) and the Ben group (week 24 vs. baseline, P>0.05). UP and UAlb/Cr were increased in the TCM group to week 12, then were stable (week 24 vs. baseline, P<0.05). The hemoglobin in the TCM group was also improved (week 24 vs. baseline, P<0.05). The accumulative survival rate in the TCM+Ben group was higher than that in the TCM group and the Ben group (P=0.044). Side effects in the TCM group were the lowest in these groups (P<0.05). The patients with dry cough in the TCM+Ben group and the Ben group were increased as compared with the TCM group (P<0.05). Hyperkalemia happened less frequently in the TCM group as compared with the other two groups (P=0.052). CONCLUSIONS: For the patients with CKD stage 3, TCM can improve eGFR and hemoglobin with lower side effects. Benazepril significantly decreased the proteinuria. Chinese medicine integrated with benazepril can ameliorate renal function and decrease proteinuria synergistically.

[Effects of Shensu II Recipe on the expressions of transforming growth factor-beta1, and plasminogen activator inhibitor-1 in the focal segmental glomerulosclerosis rats].

OBJECTIVE: To observe the effects of Shensu II Recipe on the renal function, mesangial extracellular matrix (ECM) accumulation, the expressions of transforming growth factor-beta1, (TGF-beta1), and plasminogen activator inhibitor-1 (PAI-1) in the focal segmental glomerulosclerosis (FSGS) rats. METHODS: FSGS SD rat model was induced by injecting adriamycin. They were randomly divided into the model group, the Western medicine group, and the Chinese medicine group according to body weight. Besides, another 12 rats was taken as the blank control group. Of them, benazepril (0.33 mg/100 g) was given to rats in the Western medicine group by gastrogavage, while Shensu II Recipe (3.5 g/100 g) was given to rats in the Chinese medicine group by gastrogavage. Normal saline was given to rats in the control group and the model group by gastrogavage. Six rats died during the experiment process, among which, one in the control group, two in the model group, one in the Western medicine group, and two in the Chinese medicine group. The changes of 24 h urinary protein (24 hU, pyrogallol red method), blood urea nitrogen (BUN, urease method), serum creatinine (SCr, enzymatic assay of creatinine), serum total protein (TP, biuret colorimetry), serum albumin (ALB, bromocresol green colormetry) were detected. The pathomorphological changes of the glomerulus were observed. Fibronection (FN), collagen IV (Col IV), glomerulus sclerosis index (GSI), ECM/glomerulus area (GA), expressions of TGF-beta1, and PAI-1 were determined by semi-quantitative analysis. RESULTS: At the end of the 12th week, improvement was shown in the Chinese medicine group (24 hU: 38.55 +/- 2.49 mg; BUN:10.87 +/- 1.78 mmol/L; SCr: 51.70 +/- 1.50 micromol/L; TP: 68.28 +/- 2.31 g/L; and ALB: 42.43 +/- 1.95 g/L). The pathomorphological observation showed that the development of glomerulosclerosis (GS) was significantly slowed down. Semi-quantitative analysis showed significant difference when compared with the model group (GSI: 1.68 +/- 0.33 grade; ECM/GA: 7.11% +/- 2.46%; FN: 4.15% +/- 1.55%; Col IV:1.47% +/- 0.48%; TGF-beta1:19.70% +/- 5.05%; PAI-1: 22.57% +/- 10.65%) ( P < 0.05, P < 0.01). CONCLUSION: Shensu II Recipe could postpone the development of GS in FSGS rats possibly through inhibiting the expressions of TGF-beta1 and PAI-1, hindering the over-accumulation of mesangial matrix.

[Effects of shenshuning recipe on expression of hepatocyte growth factor in rats with glomerulosclerosis].

OBJECTIVE: To investigate the effects of Shenshuning Recipe (SSNR) on gene expression of hepatocyte growth factor (HGF) in renal tissues in rats with glomerulosclerosis. METHODS: Glomerulosclerosis was induced in 42 rats by unilateral nephrectomy and intravenous injection of doxorubicin. Then these 42 rats were randomly divided into three groups: untreated group, SSNR-treated group and benazepril-treated group. Another eight rats were included into sham-operation group. The rats in the SSNR-treated group and the benazepril-treated group were fed SSNR or benazepril respectively for 8 weeks. The levels of 24 h urine protein (Upr), serum creatinine (Cr) and blood urea nitrogen (BUN) of rats in each group were examined. The renal morphological changes were observed under microscope, and the diameter of glomerular capillary, mesangial matrix and glomerulosclerosis index were analyzed by image analysis software. Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect the gene expression of HGF in the renal tissues. RESULTS: The levels of 24 h Upr, serum Cr and BUN in the untreated group were remarkably increased than those in the sham-operation group (P<0.01). The pathological morphological changes in the untreated group showed that the glomerulosclerosis was diffused around the renal tissue and the capillaries were shrunk. The expression level of mesangial matrix was up-regulated and the glomerulosclerosis index was 3.32+/-0.35. The expression level of HGF mRNA in the untreated group was obviously lower than that in the sham-operation group (P<0.05). The levels of 24 h Upr, serum Cr and BUN in the SSNR-treated group and the benazepril-treated group were remarkably decreased as compared with those in the untreated group, while the expression levels of HGF mRNA were both obviously higher than that in the untreated group (P<0.01). The pathological morphological changes in the SSNR-treated group and the benazepril-treated group were both alleviated. There was no significant difference in therapeutic effect between the SSNR-treated group and the benazepril-treated group. CONCLUSION: Shenshuning Recipe can up-regulate the expression of HGF mRNA, decrease the mesangial matrix, and improve the renal function, so that it may retard the development of glomerulosclerosis.